Interest Groups

Faculty

  • Accili Domenico

    • Russell Berrie Foundation Professor of Diabetes
    Affiliation
    • Medicine-Endocrinology
    Expertise
    • Insulin action
    • endocrine pancreas
    Research Statement

    Dr. Accili’s research has delved into the pathogenesis of diabetes, the integrated physiology of insulin action and the mechanisms of pancreatic beta-cell failure. He is best known for the identification of a family of DNA-binding proteins that collectively regulate diverse pathophysiological processes, including liver glucose production, food intake, insulin production and adipogenesis. He is funded by NIDDK to conduct this work. He has been active in the NIDDK diabetes program for many years. Most recently, he has chaired the Beta Cell group for the Strategic Plan Initiative. Since 2011, he has served on the NIDDK Advisory Council.

    Interest Group

    Beta cell function and replacement, Integrated physiology, Diabetes Dyslipidemia and Heart disease

    Primary Core Use
    • All
    Secondary Core Use
    • All
    Key Collaborations

    HAEUSLER, QIANG, WARDLAW, TALL, PAJVANI, LEIBEL, WELCH, MCGRAW, GU, TABAS, FERRANTE, BLANER, CREUSOT, DECKELBAUM

  • Leibel Rudolph

    • Christopher J. Murphy Professor of Diabetes Research
    Affiliation
    • Pediatrics-Molecular Genetics and Medicine
    Expertise
    • Genetics of Complex disorders
    • Obesity and diabetes
    • Stem cell biology
    Research Statement

    Dr. Leibel has worked in diabetes and obesity research for over 25 years. His initial research efforts were focused on adrenergic receptor-mediated effects on lipolysis, and on the control of fatty acid re- esterification in human adipose tissue. In 1985 Dr. Leibel and his associates (then at Rockefeller University) began a series of experiments to produce molecular maps of mouse single gene obesity mutations: ob, db, fat and tub. These efforts, in collaboration with the Friedman laboratory at Rockefeller, led to the cloning of the ob (leptin) gene in 1994. This discovery, by identifying a major signal of adipose tissue mass to the brain, has had an important impact on obesity research in animals and humans. Dr. Leibel’s group has subsequently worked out the fine structure of many of the genes in the leptin response pathway, and in collaboration with investigators around the world, have studied the contribution of allelic variation in these genes to aspects of body composition, obesity and type 2 diabetes in humans. During the past 8 years, Leibel has worked with clinicians at Columbia (Goland) and scientists at NYSCF (Egli) to create insulin-producing cells from fibroblasts-derived iPS cells. These cells are being used to characterize the cellular basis for various clinical types of diabetes and obesity.

    Interest Group

    Beta cell function and replacement, Integrated physiology

    Primary Core Use
    • All
    Secondary Core Use
    • All
    Key Collaborations

    ACCILI, CHUNG, EGLI, GOLAND, HARRIS, ROSENBAUM, WARDLAW, ZHANG,FREEBY

  • Abrams Elaine

    • Professor of Epidemiology and Pediatrics
    Affiliation
    • Department of Pediatrics
    Research Statement

    Dr. Abrams is Professor of Pediatrics and Epidemiology at Columbia University and the Senior Director for Research at ICAP at the Mailman School of Public Health. She has worked in perinatal and pediatric HIV prevention and treatment for over thirty years as a clinician, researcher, and public health practitioner. She has extensive experience in the design, implementation, and analysis of antiretroviral treatment (ART) studies of pregnant/postpartum women, infants, and children. She is a longstanding member of US panels determining recommendations for treatment for both pregnant women and children with HIV infection. She has also advised national governments and technical working groups. She has a study underway to understand the obesogenic and diabetogenic effects of Dolutegravir (DTG)- based antiretroviral therapy in South Africa. For this NIDDK-funded study, she will benefit from interactions with the
    DRC research base, and take advantage of the TBAC for assay development and consultation on the best outcome measures. She will also participate in Program Enrichment activities by giving seminars and being available to supervise trainees.

    Interest Group

    Global had and disparities

    Primary Core Use
    • TBAC
     
  • Albrecht Sandra

    • Assistant Professor of Epidemiology

    Affiliation

    • Mailman School of Public Health - Epidemiology

    Research Statement

    Dr. Albrecht is formally trained as a social epidemiologist, with additional training in the nutritional and population health sciences. Her research focuses on the socio-cultural and neighborhood-level factors that contribute to the high burden of nutrition-related diseases in US immigrants and among Hispanics/Latinos using a variety of quantitative data sources. Past research projects include applying longitudinal and multi-level modeling approaches to investigate the social determinants of diet and weight gain, and exploring the role of ethnic enclaves in shaping nutrition-related outcomes, including type 2
    diabetes (T2D). With funding from an NIH/NIDDK Career Development Award (K01), Dr. Albrecht’s emerging line of research seeks to understand the social
    and behavioral mechanisms underlying the high burden of T2D and associated complications among diverse groups of Hispanics/Latinos, with an emphasis on
    improving access to quality care, and affordable, healthy food. Given her background and expertise, Dr. Albrecht is well suited to serve as a member of
    Columbia University’s Diabetes Research Center. In particular, access to the translational biomarker analytical core to assay key markers of glucose
    metabolism will be critical for future projects that combine biomedical and socioecological approaches to improve understanding of the drivers of progression to
    and from T2D among Hispanic/Latino populations.

    Interest Group

    • Gloabal  health and disparities

    Primary Core Use

    • TBAC
  • Alonso Laura

    • Professor of Medicine

    Affiliation

    Weill-Cornell Medical School

    Research Statement

    "Dr. Alonso wrote: “As an endocrinologist and physician-scientist with a clinical practice in diabetes, I am all too familiar with the challenges and pain, sometimes literally, that insulin deficiency brings to my patients. I feel incredibly lucky to be also working towards a long-term solution to this problem in the laboratory. As an endocrine fellow I had the great fortune to train in stem cell biology with Elaine Fuchs, dissecting the role of Sgk3 in hair follicle cellular dynamics. At the University of Pittsburgh, under the guidance of Andy Stewart I entered the pancreatic islet field with a K08 to study the effects of in vivo mouse hyperglycemia as a model of beta cell mass expansion in the living pancreas. My lab’s research contributions to date are centered on nutrient impact on beta cell replication (glucose, lipids), exploration of the cell cycle inhibitory CDKN2A/B GWAS locus, and ER stress and the beta cell Unfolded Protein Response (UPR). Our most impactful observation to date identified the UPR as a cell-intrinsic sensor of hyperglycemia that triggers beta cell proliferation, the basis of much of our current focus. I moved to Weill Cornell in September, 2019, in the dual capacities of Division Chief of Endocrinology as well as Director of the Weill Center for Metabolic Health, an emerging center on campus for diabetes, obesity and metabolism research. My charge is to develop world class clinical, translational and basic research in the sphere of metabolism, a task made easier by the already outstanding scientists and trainees already on campus. As a physician scientist firmly placed in the diabetes research arena, I couldn’t be more enthusiastic to be a member of the Columbia University Diabetes Research Center. Through our proximity and shared interests I interact regularly with many CU DRC members already and look forward to many productive collaborations.”

    Interest Group

    • Beta cell function and replacement

    Primary Core Use

    • ATPI

    Seconday Core Use

    • MMFP, TBAC
  • Bauer Rober

    • Assistant Professor of Medicine

    Affiliation

    • Medicine - Cardiology

    Research Statement

    Dr. Bauer's long-term research goal is to understand disease pathophysiology to inform novel treatments for cardiometabolic disease conditions. His scientific
    research centers on the functional characterization of human genetics data in both in vitro and in vivo models of disease, initially in rare mendelian disorders
    but more recently in complex, common traits such as dyslipidemia and cardiovascular disease. His research program, housed in the newly established Cardiometabolic Genomics Program (CGP) at Columbia University, combines genetics and lipid metabolism, physiology, and atherosclerosis to investigate
    novel genomic loci identified by human genome-wide association studies (GWAS) as associated with human plasma lipid metabolism and coronary artery disease (CAD). The main current research focus is the pseudokinase Tribbles-1 (TRIB1) and its function in regulating metabolism and metabolic disease via action in hepatocytes and adipocytes. Additional projects in the lab focus on studies of the transcription factor C/EBPα and its role in hepatic lipid metabolism, functional genomic analysis of lipoprotein GWAS loci, adventitial cell involvement in atherosclerosis, and the role of the matrix metalloproteinase ADAMTS7 in coronary artery disease. For these projects, he will crucially depend on access to virtually all DRC Core Facilities. He's an active participant to Program Enrichment activities and a sought-after mentor.

    Interest group

    • Diabetes dyslipidemia heart disease

    Primary Core Use

    • ATPI

    Secondary Core Use

    • MMFP
  • Blaner William

    • Professor of Medicine

    Affiliation

    • Medicine-Preventive Medicine and Nutrition

    Expertise

    • Retinoids

    Research Statement

    The Blaner laboratory studies the role of retinoic acid signaling. They have been involved in key studies of RBP4 and its rtole in insulin resistacne. More recnelty, they have explored the role of retinoids in insulin secretion from pancreatic β-cells. The specific hypothesis being addressed is that ablation of retinoic acid/retinoic acid receptor (RAR) signaling in β-cells in adult mice impairs glucose-stimulated insulin secretion and that this is associated with a decrease in β-cell mass. Study of RARdn transgenic mice, where transgene expression was induced at 3 months of age, establishes that there is a marked downregulation of expression of the known retinoic acid- responsive genes Cyp26a1, Stra6 and CrbpI in isolated islets obtained from these mice. These observations are consistent with the notion that expression of the RARdn transgene effects islet glucose sensing and insulin gene expression. Surprisingly, the RARdn expressing mice are euglycemic and show no differences in their responses to glucose tolerance tests compared to matched control mice. The basis for this unexpected but potentially very significant finding is currently being investigated by the laboratory.

    Interest Group

    Beta cell function and replacement, Integrated physiology

    Primary Core Use

    • MMTP

    Secondary Core Use

    • ATPI

    Key Collaborations

    GOLDBERG, BERK, JIANG, KARSENTY, GINSBERG, ACCILI

  • Bogun Magdelena

    • Assistant Professor of Medicine

    Affiliation

    • Medicine - Endocrinology

    Research Statement

    Dr. Bogun is an experienced clinician and clinical investigator in both type 1 and type 2 diabetes. She takes care of patients at the Naomi Berrie Diabetes Center and directs the inpatient diabetes service at the New York Presbyterian Hospital of Columbia University Irving Medical Center. She is a co-investigator on multiple NIH and industry funded multi-center projects for type 1 and type 2 diabetes. She received an NIH-TrialNet Emerging Leader Award to study the fall of C-peptide as a marker of endogenous insulin secretion in individuals before developing clinical type 1 diabetes. This research showed that insulin secretion falls significantly 6 months before clinical diagnosis of type 1 diabetes. This information is guiding the design of studies to administer therapies that prevent the fall in endogenous insulin secretion. She has experience in conducting quality improvement projects for patients with diabetes. She received a P&F award to implement CGM-based remote monitoring of glycemia in the ICU in patients admitted with DKA. This project will lead to significant savings and streamlining of standards of care and will be essential as COVID-positive patients continue to be admitted with DKA.

    Interest Group

    • Genetics and Immunology of T1D

    Primary Core Use

    • TBAC
  • Califano Andrea

    • Professor of Biomedical Informatics

    Affiliation

    • Department of Biomedical Informatics

    Research Statement

    Dr. Califano is the Clyde and Helen Wu Professor of Chemical and Systems Biology and the founding Chair of the Department of Systems Biology at Columbia University. He applies physics-based approaches, including extensive use of information theory, to reverse engineering and interrogation of gene regulatory networks. He has pioneered use of mammalian networks as models for the quantitative analysis of cancer related phenotypes and for identification of driver genes, driver mutations, and small-molecule modulators of tumor vulnerabilities. In particular, he has demonstrated that (a) diabetes-specific transcriptional and signaling networks can be inferred accurately using information theoretic principles from large collections of molecular profile data of patient-derived islet samples, using algorithms developed by his lab such as ARACNe; (b) these networks can be interrogated using tumor derived signatures to discover master regulators (MRs) of tumor progression and drug sensitivity; (c) inhibition of MRs using individual compounds or synergistic compound combinations, as computationally inferred from perturbational signatures, can restore islet function in vitro and in vivo . Originally validated in cancer and stem cells, these methodologies represent one of the most extensive and validated toolkits for the systems biology-based elucidation of novel targets, smallmolecule inhibitors, and biomarkers. He has received a P&F grant to apply these methods to diabetes and is currently involved in a follow-up study of unbiased compound library screening to identify new therapeutics in diabetes. He utilized extensively all Cores since his laboratory doesn’t normally perform metabolicwork. Without DRC support, this work would not have taken place.

    Interest Group

    • Beta cell function and replacement

    Primary Core Use

    • MMFP, CCSC

    Secondary Core Use

    • ATPI

    Key Collaborations

    Accili, Alonso, Kuo

     

  • Chen Xiaojuan

    • Assistant Professor of Surgical Sciences

    Affiliation

    • Surgery & Center for Clinical and Translational Immunology, Columbia University

    Expertise

    • Beta Cell differentiation

    Research Statement

    Trained as a physician and a scientist, I have a long-standing interest in human islet cell pathophysiology for the understanding of diabetes onset and development, and in islet cell transplantation for the treatment of diabetes. Over the years, my laboratory has established various in vitro cell culture and in vivo islet transplantation models for studying islet cell function, survival, gene expression and regeneration. Our research is currently focused on understanding the potential role of human islet alpha cells played in the development of diabetes, and on characterizing the immunogeneicity of islet cells. In addition, I am collaborating with investigators at Columbia on several projects including generating functional mature beta cells from human inducible pluripotent stem cells, and inducing immune tolerance to islet allo- or xenografts in non-human primates. Previously, as the Director of the Human Islet Isolation and Transplantation Laboratory at Northwestern University, I performed islet isolation for research and clinical transplantation from>180 human pancreata where I optimized this technique and became an expert in the exacting methodology and compliance procedures required for FDA approved clinical cellular therapies. Since joining CCTI at the Columbia University Medical Center as the Director of Islet Transplantation, I have trained and directed my team in performing islet isolation from mouse, monkey, pig and human pancreata, and in characterizing islet function and survival in vitro and in vivo by transplanting them into diabetic mice. Besides transplant tolerance induction studies, I am also pursuing basic research on improving islet cell engraftment after transplantation.

    Interest Group

    Beta cell function and replacement

    Primary Core Use

    • ATPI

    Secondary Core Use

    • TBAC

    Key Collaborations

    Sykes, Creusot, Harris, Egli, Leibel, Goland

  • Choi Eunhee

    • Assistant Professor of Pathology and Cell BiologyDept of Pathology&Cell Biology
  • Colecraft Henry

    • Professor of Physiology

    Affiliation

    • Physiology & Cellular Biophysics

    Research Statement

    Dr. Colecraft investigates regulation of ion channels that underlie the electrical activity of neurons and cardiac myocytes. He has made seminal contributions to current understanding of mechanisms underlying regulation of CaV1/CaV2 channels by auxiliary b subunits, small G-proteins, and protein kinase A. He has developed novel methods to: manipulate and study structure-function mechanisms of CaV1.2 channels directly in adult cardiomyocytes using splitintein trans-splicing of pore-forming a1C subunits; visualize and quantify CaV channel surface trafficking using quantum dot labeling and flow cytometry; engineered novel genetically encoded CaV channel blockers; achieve selective post-translational functional knockdown of ion channels using engineered ubiquitin ligases; developed novel nanobody binders for CaVb subunits that permit development of CaV1/CaV2 channel modulators with unprecedented levels of specificity. Several of these methods have been widely adopted by other scientists and colleagues in the field. We have patents on; 1) compositions and methods for using engineered deubiquitinases for probing ubiquitin-dependent cellular processes, 2) compositions and methods for genetically- encoded blockers for high-voltage-activated calcium channels using engineered ubiquitin ligases, 3) nanobodies for auxiliary votage-gated calcium channel b subunits, and 4) drug target for preventing pathological calcium overload in cardiomyocytes and methods of screening for same. I have successfully administered several projects that required staffing, budgeting, and setting up research collaborations with other investigators. His diabetes-related research focuses on dissecting the role of ion channels in pancreatic beta cell physiology and dysfunction, as well as creating novel genetically-encoded calcium channel blockers for potential treatment of diabetes-induced neuropathic pain. He was funded by a P&F grant to perform this work, and has extensivley used Core facilities. His involvement is ongoing and extends to Enrichment Program activities.

    Interest Group

    • Beta cell function and replacement

    Primary Core Use

    • ATPI

    Secondary Core Use

    • MMFP, TBAC

    Key Collaborations

    Marks, Blaner, Kuo

  • Cook Joshua

    • Assistant Professor of Medicine

    Affiliation

    • Medicine - Endocrinology

    Research Statement

    Dr. Cook is a physician-scientist dedicated to understanding the pathophysiology and treatment of insulin resistance underlying type 2 diabetes and its cardiovascular complications. His doctoral research focused on dissecting mechanisms of insulin resistance in mice and isolated mouse hepatocytes. He
    demonstrated that the “selective” hepatic insulin resistance at play in the metabolic syndrome – unchecked glucose production and increased lipid biosynthesis – can be induced by excessive insulin signaling and involves dissociation of the transactivator and co-regulatory functions of insulinresponsive transcription factor FoxO1. His current objective is to extend these studies to humans through the Columbia University Medical Center DRC and utilizing Pilot and Feasibility funding from DRC, while also seeing patients with lipid disorders and insulin resistance one-half day per week. Taking advantage of his dual training in clinical endocrinology and laboratory research, he’s embarking on an investigation of how acute insulin resistance affects lipid metabolism by studying patients using cancer treatments that directly interfere with the insulin signaling pathway. In order to accomplish this translational metabolic research study, he has brought together an interdisciplinary team of both clinicians and basic scientists. For recruitment of patients, he has established collaborations with clinical oncologists. On the basic research side, he will continue a successful collaboration with Dr. Haeusler that is presently funded by a special R01 supplement for physician/scientists. Her expertise in lipid and bile acid metabolism will prove vitally important for obtaining and interpreting the data gathered from human subjects. He will continue to utilize Cores and participate in the Enrichment Program.

    Interest Group

    • Diabetes dyslipidemia heart disease

    Primary Core Use

    • TBAC

    Secondary Core Use

    • CCSC

    Key Collaborations

    Haeusler, Tabas, Tall, Ginsberg

  • Creusot Remi

    • Assistant Professor of Medical Sciences

    Affiliation

    • Center for Clinical and Translational Immunology, Columbia University

    Expertise

    • Diabetes and autoimmunity

    Research Statement

    The goals of my research are to understand the mechanisms behind the impaired induction or maintenance of immune tolerance in individuals with autoimmune disease, and ultimately, to devise more efficient, more targeted and safer therapeutic approaches to restore long-term immune tolerance, a likely prerequisite for curing autoimmunity. His expertise spans over 17 years in studying T cell responses in immunity and tolerance settings, with 13 years devoted to understanding the pathogenesis and developing cell-based and antigen-specific therapies in Type 1 diabetes (T1D). The major focus of my research has been on tolerogenic stromal and dendritic cells, the regulation of diabetogenic T cell responses in the pancreatic lymph nodes (PLNs), the balance between immunogenic and tolerogenic processes, and between pathogenic and regulatory T cells, in the context of beta cell antigen presentation, the mechanisms underlying these processes, and the development of approaches to specifically target diabetogenic T cells for tolerance. His lab uses flow cytometry as the primary research tool to investigate the response of antigen-specific T cells in steady-state maintenance of tolerance and in antigen-specific immunotherapies. He has personally operated five models of flow cytometry analyzer, two models of cell sorter and three different acquisition and analysis programs. Additionally, he has an extensive knowledge and experience with fluorochromes, fluorescent proteins, and cell proliferation / viability dyes used in flow cytometry, as well as panel design and troubleshooting. He frequently assists other DRC faculty members who have limited experience with or infrequent need of flow cytometry.

    Interest Group

    Beta cell function and replacement

    Primary Core Use

    • CCS

    Secondary Core Use

    • MMTP

    Key Collaborations

    Egli, Accili, Sykes, Pajvani, Qiang, Chen, Goland

  • Diano Sabrina

    • Professor of Physiology

    Affiliation

    • Physiology & Cellular Biophysics

    Research Statement

    Dr. Diano’s research has been focusing on role of the Central Nervous System in the regulation of food intake, energy and glucose homeostasis. She has a broad
    background in neuroendocrinology, with specific training and expertise in key areas related to this research project. As a postdoctoral fellow, she carried out research on the effect of several hormones on CNS circuits that regulate metabolism and reproduction, including the melanocortin system. As faculty and PI and co investigator of several NIH-funded, she focused her research in the field of neurobiology of energy metabolism. In addition, she successfully managed large collaborative projects (e.g. staffing, research protections, budget), collaborated with other researchers, and produced several peerreviewed publications from each project. She has a record of productive research projects in an area of high relevance for the DRC. She has made extensive use of Core facilities, especially the MMFP and ATPI. As Head of the Institute of Human Nutrition she also plays a key role steering trainees toward diabetes research.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • MMFP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Ferrante, Leibel, Emiliano, Zeltser, Zhang, Zuker

  • Doege Claudia

    • Assistant Professor

    Affiliation

    • Pediatrics-Molecular Genetics

    Expertise

    • Beta cell function and replacement

    Research Statement

    Dr. Doege is a newly-appointed tenure-track investigator whose main interest and expertise are in the generation of patient-specific iPS cells to be converted into cell types of metabolic interest, inclduing neurons and pancreatic beta cells.

    Interest Group

    Beta cell function and replacement

    Primary Core Use

    • CCS

    Secondary Core Use

    • ATPI

    Key Collaborations

    Leibel, Egli, Sui, Goland

  • Ducy Patricia

    • Assistant Professor

    Affiliation

    • Genetics and Development

    Expertise

    • Osteocalcin and beta cell biology

    Research Statement

    Patricia Ducy identified Runx2 as a major regulator of cell differentiation during skeleton development and demonstrated that bone formation is centrally regulated by a leptin-dependent mechanism. More recently, she and Dr. Karsenty showed that osteoblasts, the bone-forming cells, regulate energy metabolism by secreting a novel hormone, osteocalcin, and that gut- derived serotonin is a major regulator of bone mass accrual. Her research uses a combination of molecular biology, mouse genetics, and physiology to analyze the molecular mechanisms controlling bone cells differentiation and skeleton homeostasis. She has used and plans to continue to use multiple Core facilities.

    Interest Group

    Beta cell function and replacement

    Primary Core Use

    • MMTP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Karsenty, Kousteni, Levine

  • Egli Dieter

    • Assistant Professor

    Affiliation

    • Pediatrics

    Expertise

    • Stem cells and diabetes

    Research Statement

    My laboratory uses stem cells to investigate the cellular and molecular biology of diabetes, and to develop cell replacement therapies for diabetics. Diabetes is a disorder characterized by a loss of beta cell mass, and/or a loss of beta cell-autonomous function, leading to a deficiency of insulin and deranged regulation of blood glucose. In type 1 diabetes (T1D), loss of beta cell mass is caused by an autoimmune assault. Because of the limited ability of beta cells to regenerate, even if inhibition of the autoimmune response to beta cells were successful, beta cell mass and adequate glucose-regulation are unlikely to fully recover. Therefore, an exogenous source of beta cells for transplantation could be therapeutically useful. To generate such cells, I am developing a reprogramming technique using human oocytes.

    Interest Group

    Beta cell function and replacement

    Primary Core Use

    • ATPI

    Secondary Core Use

    • CCS

    Key Collaborations

    Chung, Goland, Leibel 

  • Emiliano Ana

    • Assistant Professor of Medicine

    Affiliation

    • Medicine - Endocrinology

    Research Statement

    Dr. Emiliano is a physician-scientist and faculty member in the Endocrinology Division at Columbia University. She established her laboratory at Columbia University in the spring of 2019 to study the role of the peripheral nervous system in glucose and energy homeostasis, and how sex and age influence that
    role. As part of that research program, she studies the effects of weight loss surgeries on the peripheral nervous system, using obese mouse models. her laboratory has the expertise to perform both Sleeve Gastrectomy and Roux-en-Y gastric bypass, the two most frequently performed weight loss surgeries in human patients in the US, as well as complex microinjections for genetic manipulations, and dissections in various parts of the peripheral nervous system, using mouse models. This expertise allowed her to discover that sleeve gastrectomy leads to degeneration of the mouse celiac-superior mesenteric ganglia neurons (CSMG). The CSMG are cluster of sympathetic neurons that lie close to the stomach and innervate stomach, liver, pancreas, and mesenteric white adipose tissue, among other tissues. Little is known about the role of CSMG neurons in the control of glucose and energy homeostasis, despite their extensive sympathetic projections to organs involved in metabolism. In addition to sleeve gastrectomy-induced CSMG neuronal degeneration, we also found that performing CSMG resection in obese mice leads to the same degree, or better, of weight loss and blood glucose improvement compared to sleeve gastrectomy. Thus, her group has uncovered a potential new mechanism of action through which sleeve gastrectomy promotes weight loss and blood glucose lowering. More importantly, her group is now focused on understanding the role of CSMG neurons in glucose and energy homeostasis, which is the topic of this proposal. This work will advance the field of glucose and energy homeostasis and can
    become the basis for novel obesity therapies. She has leveraged MMFP, ATPI, and TBAC, and will continue to do so. Her novel bariatric surgery approached in experimental animals have now been incorporated in the MMFP service line, and she has been appointed co-Director of the Core.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • MMFP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Ferrante, Leibel, Diano, Zeltser, Zuker

  • Ferrante Anthony

    • Dorothy & Daniel Silberberg Associate Professor of Medicine

    Affiliation

    • Medicine-Preventive Medicine and Nutrition

    Expertise

    • Innate immunity and metabolism

    Research Statement

    Work in the Ferrante Laboratory has revealed that the immune system recognizes and responds to changes in metabolic function. Studies in the laboratory focus on how the immune and metabolic systems interact. For several decades it was known that obesity and related metabolic disorders increase the concentration inflammatory molecules found in the circulation and in key metabolic tissues. Studies in the Ferrante Laboratory revealed that the obesity-induced increases in inflammation are part of a complex immune response in which macrophages, T-cells and NK cells are recruited to metabolic organs and tissues during the development of \obesity, diabetes and non-alcoholic fatty liver disease. Much of the current work in the Ferrante Laboratory is focused on identifying and characterizing the immune cell populations that are altered by obesity and how the immune system regulates metabolism. By determining the adaptive and pathological functions of the immune system in metabolism, the laboratory identifies cells, pathways and molecules that are candidate targets for therapeutic interventions and that can be used to predict metabolic outcomes. Dr. Ferrante leads a DRC Core and is a member of the DRC Executive Committee.

    Interest Group

    Integrated physiology

    Primary Core Use

    • MMTP

    Secondary Core Use

    • CCS

    Key Collaborations

    Accili, Leibel, Ozcan, Pajvani, Qiang, Egli, Sykes, Tabas

  • Freda Pamela

    • Associate Professor of Medicine

    Affiliation

    • Medicine-Endocrinology

    Expertise

    • Growth hormone and IGFs in pituitary

    Research Statement

    This investigator conducts clinical and translational research in patients with pituitary tumors and pituitary hormone deficiency. One focus of our research is to understand the metabolic abnormalities in acromegaly, in particular insulin resistance, and body composition, a clinical marker of GH action in acromegaly, in relation to specific levels of insulin-like growth factor I (IGF-I) during treatment with the growth hormone receptor antagonist, pegvisomant and during surgical and somatostatin analog therapy.  We are currently examining body composition by total body MRI in patients with acromegaly and have found reductions in visceral adipose tissue, but increases in adipose tissue around muscle in these patients with GH excess. We are also examining fat within muscle, intramyocellular lipid, and within the liver, intrahepatic lipid, by magnetic resonance spectroscopy (MRS) in patients with acromegaly undergoing surgery and other forms of medical therapy.  A focus of this study is to understand the role of fat distribution in causing the insulin resistance of acromegaly and its recovery during therapy. This ongoing study was previously funded by a DRC Pilot and Feasibility Award.

    Interest Group

    Integrated physiology

    Primary Core Use

    • TBAC

    Secondary Core Use

    • N/A

    Key Collaborations

    Wardlaw, Korner, Ferrante, Goland

  • Gallagher Dympna

    • Professor of Nutritional Medicine

    Affiliation

    • Medicine- Endocrinology, Columbia University

    Expertise

    • Energetics and body composition

    Research Statement

    Dr. Gallagher is an Associate Professor of Nutritional Medicine, and is Director of the Human Body Composition Core Laboratory of the New York Obesity & Nutrition Research Center, whose research focuses on energetics and body composition, and the effects of body weight and body composition on health risk throughout the life cycle. Dr. Gallagher's scientific interests fall into the following categories: (a) resting energy expenditure at the organ/tissue level; (b) the composition of weight change in elderly, during growth and development (beginning at birth), and during intentional weight loss (lifestyle intervention and  bariatric surgery induced); (c) the understanding of race differences in body composition; and d) the validation of new body composition measurement instrumentation/techniques.

    Interest Group

    Integrated physiology

    Primary Core Use

    • TBAC

    Secondary Core Use

    • N/A

    Key Collaborations

    Freda, Pi-Sunyer, Laferrere, St.Onge, Leibel, Wardlaw, Ginsberg

  • Gangwisch James

    • Assistant Professor

    Affiliation

    • Department of Psychiatry

    Expertise

    • Sleep duration and metabolic syndrome

    Research Statement

    James Gangwisch, Ph.D. is an Assistant Professor at the Columbia University, College of Physicians and Surgeons, Department of Psychiatry, Division of Cognitive Neuroscience and a Research Scientist at the New York State Psychiatric Institute. He has over ten years of clinical experience as a psychotherapist in inpatient, outpatient, and research psychiatric settings. His research has focused on the relationship between sleep duration and diseases associated with the metabolic syndrome – obesity, hypertension, and diabetes. The study that he led linking inadequate sleep to obesity helped motivate the National Institutes of Health  to release a request for proposals on “The Mechanisms Linking Short Sleep Duration and Risk of Obesity or Overweight”. He led the first study to show an association between short sleep duration and hypertension incidence (American Heart Association journal Hypertension). Dr. Gangwisch serves as a peer reviewer for numerous medical journals and is actively involved with the DRC program enrichment activities.

    Interest Group

    Global health, health disparities, and underserved urban populations

    Primary Core Use

    • TBAC

    Secondary Core Use

    • N/A

    Key Collaborations

    Heyer, Walsh, Mayer, Small

  • Ginsberg Henry

    • Herbert and Florence Irving Professor of Medicine

    Affiliation

    • Medicine-Preventive Medicine and Nutrition

    Expertise

    • Lipoproteins, atherosclerosis

    Research Statement

    Dr. Ginsberg conducts research related to the regulation of the levels and metabolism of apolipoprotein B-containing lipoproteins, the lipoproteins carrying triglycerides and the bulk of cholesterol in blood. These include the atherogenic very low density and low density lipoproteins. Dr. Ginsberg has a particular emphasis on the pathophysiology of hypertriglyceridemia and the dyslipidemia associated with insulin resistance and diabetes mellitus. Research is conducted at three levels: tissue culture using both human and rat hepatoma cells, transgenic mice, and human clinical studies. In cultured cells, Dr. Ginsberg and his associates have described the role of lipid substrate availability in determining if newly synthesized a of degradation and lipoprotein assembly of apoB. His group has characterized the role of the proteasome in the degradation of apoB.In transgenic mice, he had developed a model of insulin resistance and dylipidemia with many characteristics of the human disorder. This model, as well as others now in use in the lab, allow the group to dissect the important components of substrate availability and genetic control that lead to hypertriglyceridemia. Dr. Ginsberg’s group makes and studies transgenic mice, conducting whole body, cellular, and molecular experiments.In clinical studies, Dr. Ginsberg is investigating postprandial hyperlipidemia as a risk factor in patients with diabetes. He is also part of a group at Columbia that will be studying the role of glycemic, lipid and blood pressure control in the prevention of cardiovascular disease in patients with diabetes. The latter, named the ACCORD trial, is a 10-year trial with 10,000 patients at 6 sites across the United States. Dr. Ginsberg also has a long record of research into the effects of diet on lipid and lipoprotein metabolism in humans, and has conducted numerous controlled feeding studies in humans.

    Interest Group

    Diabetes dyslipidemia heart disease

    Primary Core Use

    • MMTP

    Secondary Core Use

    • TBAC

    Key Collaborations

    Di Paolo, Goldberg, Tall, Pajvani, Accili, Blaner, Tabas

  • Goland Robin

    • Merrill Eastman Professor of Clinical Medicine

    Affiliation

    • Medicine-Endocrinology

    Expertise

    • Clinical trials in type 1 and type 2 diabetes

    Research Statement

    Dr. Robin Goland directs the patient care and clinical research programs at the Berrie Center. She was instrumental in establishing the Naomi Berrie Diabetes Center in July 1998. Under the leadership of Dr. Goland and Berrie Center Co-Director Dr. Rudolph Leibel, the Berrie Center has become recognized nationally and internationally for excellence and innovation in patient care and research in diabetes. Translational research in type 1 and type 2 diabetes. Her research interest include: (1) Preservation of beta cell function in new onset type 1 diabetes; (2) Transition of pediatric patients with diabetes to adult care (3) Stem cell biology in diabete; and (4)  Treatment trials in new onset type 1 diabetes and new onset type 2 diabetes. Dr. Goland's leadership has been essential for the clinical translational of key DRC projects, including: PET imaging of pancreatic islets; development of iPS from skin fibroblasts of patients with  auotimmune diabetes as well as monogenic forms of diabetes and obesity; progression of immune response in new-onset type 1 diabetics; and role of Fc receptors in modulating autoimmunity. Dr. Goland leads several ongoing translational and clinical outcome studies in both type 1 and type 2 diabetes.

    Interest Group

    Beta cell function and replacement

    Primary Core Use

    • TBAC

    Secondary Core Use

    • N/A

    Key Collaborations

    Leibel, Harris, Rosenbaum, Creusot, Sykes, Egli, Ferrante, Gallagher, Pi-Sunyer

  • Goldberg Ira

    • Edgar and Clarissa Bronfman Professor of Medicine

    Affiliation

    • New York University

    Research Statement

    Dr. Goldberg’s research has been focused on the relationship of lipids to diabetes, studying the basic pathways of tissue lipid uptake, how lipids are
    required for energy, and how excess fatty acid uptake causes lipotoxicity. They created mice with a number of defects in lipid metabolism including deletions in the triglyceride hydrolysis enzyme lipoprotein lipase (LpL), CD36 a fatty acid transporting protein, and other lipid metabolic enzymes. In addition, they have created models of cardiac toxicity due to overexpression of LpL and PPARgamma in the heart and developed methods to correct this toxicity by altering cardiac fatty acid uptake and by changing diacylglycerol and ceramide metabolism. Other studies in the laboratory are focused on how diabetes affects vascular disease. These studies showed that atherosclerosis regression (the repair of atherosclerosis arteries after cholesterol reduction) is abnormal in diabetic rodents. In addition, we showed that circulating white blood cells are increased with hyperglycemia and obesity, and this increase is due to a more proliferative bone marrow. They also reported that cardiovascular disease in patients with type 1 diabetes is associated with higher circulating white blood cell counts and that bariatric surgery markedly reduces white blood cells. Dr. Goldberg was on the Columbia faculty for many years, and continues to interact with the DRC using the ATPI and MMFP Cores, in addition to contributing to the Enrichment Program. He plans on continuing these activities.

    Interest Group

    • Diabetes dyslipidemia heart disease

    Primary Core Use

    • MMFP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Haeusler, Tabas, Tall, Ginsberg, Reilly, Reyes-Soffer

  • Griesemer Adam

    • Professor of Pediatrics

    Affiliation

    • Pediatrics

    Research Statement

    Dr. Griesemer is Principal Investigator at the Columbia Center for Translational Immunology and Assistant Professor of Surgery in the Division of Abdominal Organ Transplantation. His research is focused on two goals: 1) Eliminating the need for transplant recipients to take life-long immunosuppression and; 2) Finding solutions to the shortage of donor organs relative to the number of patients that can benefit from transplantation. His laboratory performs translational research in large animal models aimed at bringing tolerance strategies closer to clinical trials. He has performed bone marrow, kidney and liver transplants in baboons, cynomolgus and rhesus macaque models with the intent of inducing tolerance to the solid organ. He has also examined the immune response to the transplant to understand mechanisms of tolerance or rejection, allowing him to design protocol modifications to increase the success and decrease the toxicity of the conditioning regimen. Although mixed chimerism has been the most successful strategy to induce tolerance to renal transplants in humans, the lack of durable chimerism decreases the rate of subsequent tolerance that is induced. His laboratory has extensively studied methods to generate autologous regulatory T cells by ex vivo expansion with the aim of enhancing donor stem cell engraftment to promote durable mixed chimerism. He has also examined the efficacy of Treg infusions for the suppression of anti-donor immune responses and for the induction of immune tolerance. He has an extensive track record of collaborative research with the other members of the DRC and has published over 25 peer-reviewed manuscripts with DRC faculty and made extensive use of the CCSC. His research background, history of collaboration with the members of the DRC, and progress to date on these studies make him a strong participant in our application.

    Interest Group

    • Genetics and Immunology of T1D

    Primary Core Use

    • CCSC

    Key Collaborations

    Sachs, Creusot, Chen, Sykes, Yamada

  • Haeusler Rebecca

    • Assistant Professor of Pathology and Cell Biology

    Affiliation

    • Pathology and Cell Biology

    Expertise

    • Bile acids, HDL cholesterol and diabetes

    Research Statement

    The goals of my research are to understand the development of proatherogenic abnormalities in lipid metabolism in insulin resistant individuals, and to identify new therapeutic targets for improving these
    abnormalities. Two key areas of focus are dysregulation of (i) high-density lipoprotein (HDL) and (ii) bile acid metabolism. HDL mediates multiple cardioprotective actions including reverse cholesterol transport (RCT). It’s unknown how HDL becomes dysregulated during insulin resistance. My laboratory’s research has uncovered a novel role of the insulin-regulated FoxO transcription factors to regulate HDL composition, HDLcholesterol levels, and catabolism of cholesterol into bile acids. Bile acids are critical for maintaining cholesterol homeostasis, and regulating hepatic glucose and lipid production. We have shown that bile acids are dysregulated during insulin resistance and type 2 diabetes in humans, and these defects may impair the normal functions of these molecules. Through these two research areas, we aim to shed light on mechanisms of metabolic abnormalities and atherogenesis in the natural history of type 2 diabetes, and to identify potential therapeutic targets.

    Interest Group

    Diabetes dyslipidemia heart disease

    Primary Core Use

    • MMTP

    Secondary Core Use

    • TBAC

    Key Collaborations

    Accili, Tall, Ozcan

  • Hirsch-Moverman Yael

    • Assistant Professor of Epidemiology

    Affiliation

    • Mailman School of Public Health - Epidemiology

    Research Statement

    Dr. Hirsch-Moverman is dedicated to preventing tuberculosis (TB) and HIV, with an emphasis on implementation science in the last 10 years. Her work spanned biomedical (including clinical trials and epidemiology) and behavioral domains (including such psychosocial issues such as adherence). Her research has concentrated on the global TB and HIV epidemics, particularly in sub-Saharan Africa, where the overlapping TB and HIV epidemics have resulted in an explosion of TB cases, as well as on hard-to-reach 40Tcommunities impacted by HIV in New York City. She applied her research efforts to expanding our understanding of missed opportunities and challenges and testing interventions to prevent TB and HIV, especially in vulnerable populations such as young children (in Africa) and priority populations most deeply impacted by HIV (in the US). In both settings her research focuses on implementation and evaluation of behavioral and programmatic innovations to strengthen TB and HIV prevention and care, with particular focus on 1) adherence to TB preventive treatment (TPT) and 2) adherence to antiretroviral treatment and pre-exposure prophylaxis (PrEP). She is the Principal Investigator of two NIAID-funded R21 awards: the DETECT study (R21AI138807) that uses mixed methods to assess diabetes mellitus prevalence and incidence as well as TB treatment outcomes in TB patients in Eswatini, and the FIRST study (R21AI153954) that is pilot testing a family-centered flexible child TB contact management model in Eswatini. Both awards require knowledge and expertise in diabetes assessment and measures of metabolic fitness. To this end, she plans to use TBAC and rely on their consultative services as well as assays. She will also participate in activities of the Global Health and Minorities interest group.

    Interest Group

    • Global and health disparities

    Primary Core Use

    • TBAC

    Key Collaborations

    Albrecht, Abrams Desvarieux, Momen-Heravi

  • Hripcsak George

    • Vivian Beaumont Allen Professor of Biomedical Informatics Chair, Department of Biomedical Informatics, Columbia University

    Affiliation

    • Biomedical Informatics

    Expertise

    • Use of bionformatics to improve diabetes treatment

    Research Statement

    I have 22 years of experience in biomedical informatics, with over 200 publications in the informatics literature. I have a long track record of developing, implementing, and studying informatics interventions. I have worked extensively in supporting clinician and patient decisions. As a board-certified internist, I have deep knowledge of medicine. I built the decision support system for Columbia’s Davies Award-winning Clinical Information System (CIS), and I designed, deployed, and continue to maintain WebCIS, one of the earliest (1998) large-scale Web-based clinical information systems, which has 7000 users entering and reviewing data on 2.5 million patients. I serve as director of informatics services for NewYork-Presbyterian Hospital. I have contributed extensively to the informatics literature, especially in the areas of clinical systems, data mining, and natural language processing. The work ranges from practical clinical studies to innovative methodological work published in the informatics, computer science, and physics literature. I have published frequently on evaluation in biomedical informatics, exploiting my master’s degree in biostatistics. I have published extensivley on methods for Facilitating Problem Solving in Diabetes Management. I am currently funded to develop theoretically-grounded, practice-based HIT interventions for facilitating effecting diabetes self-management through problem-solving, experimentation, and discovery. I interact routienly with DRC members and diabetologists and I look forward to my continuing interaction with the DRC.

    Interest Group

    Global Health, Health Disparities, and Underserved Urban Populations

    Primary Core Use

    • TBAC

    Secondary Core Use

    • N/A

    Key Collaborations

    Chung, Gloand, Luchsinger

  • Hsieh Joanne

    • Assistant Professor of Medical Sciences

    Affiliation

    • Medicine- Molecular Medicine

    Research Statement

    Dr. Hsieh is interested in how TTC39B, a locus associated with high density lipoprotein (HDL) cholesterol levels, regulates lipid metabolism and hepatocyte adaptation in insulin resistance and non-alcoholic fatty liver disease (NAFLD). Her current interest is understanding the physiological role of TTC39B and PNPLA3, which is the most important genetic determinant of NAFLD, in hepatic lipid metabolism during gestation – a period marked by insulin resistance (and commonly onset of diabetes). The Pilot & Feasibility grant received from the DRC provided funding for a project that identified a novel pathway whereby TTC39B promotes the proteasomal degradation of retinoblastoma protein (pRb) in insulin resistance. This pathway promotes hepatic lipogenic gene expression in a sexually dimorphic fashion. The Pilot & Feasibility grant therefore shaped her current research interests, which will form the basis of an upcoming R01 submission. She regularly attends DRC seminars, utilizes the ATPI and CCSC Cores, and actively collaborates with other DRC members. DRC members have provided valuable insights into her projects and her continued membership will prove invaluable as she moves into the fully independent phase of her career.

    Interest Group

    • Diabetes dyslipidemia heart disease

    Primary Core Use

    • MMFP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Haeusler, Tabas, Tall, Ginsberg

  • Johnson Lynne

    • Professor

    Affiliation

    • Medicine

    Expertise

    • Molecular imaging of diabetic complications

    Research Statement

    I have had a long interest in molecular imaging- developing applications for novel radioactive probes targeting sites in vasculature and myocardium that are important in clinical disease.  I have worked with relevant small and large animal models.  I began working with monoclonal antibodies targeting heavy chain myosin in experimental animal models of myocardial infarction and cardiac transplant rejection and in clinical trials.  I have investigated imaging tissue hypoxia, apoptosis, and integrin expression using radionuclide and more recently also optical imaging probes.  Along with our collaborators Drs Ann Marie Schmidt and Ravi Ramasamy we have developed a mAb to Receptor for Advanced Glycated Endproducts (RAGE).  RAGE is a multiligand receptor that binds a number of different ligands activating intracellular signaling important in atherosclerosis, diabetes, tumors, and neurodegenerative diseases, and lung disease. We have received funding from the NIH and JDRF to investigate the role of RAGE- directed imaging in documenting and quantifying the effect of diabetes on RAGE expression in atherosclerosis, limb ischemia, and myocardial reperfusion injury.  We have developed the model of streptozotocin induced diabetes in farm pigs and in hyperlipidemic swine (LDL receptor deficient) to look at effects diabetes on RAGE directed imaging in a large animal model as a translational step towards development of a clinical imaging probe.

    Interest Group

    Diabetes dyslipidemia heart disease

    Primary Core Use

    • TBAC

    Secondary Core Use

    • MMTP

    Key Collaborations

    Ferrante, Harris

  • Karsenty Gerard

    • Paul A. Marks Professor

    Affiliation

    • Genetics and Development

    Expertise

    • Metabolic effects of bone

    Research Statement

    The lab uses mouse genetics to identify functional connections between metabolically relevant organs. Current studies include the role of osteocalcin as a mediator of hepatic and beta cell function,a nd the role of leptin neurons in the hypothalamus, as well as the peripheral effects of leptin on bone, In another line of research the molecular elucidation of two known human genetic diseases allowed us to identify another novel physiological loop this one linking bone and the GI tract. Indeed, we have shown recently that gut-derived serotonin is a hormone whose main function is to inhibit bone formation by osteoblast.

    Interest Group

    Integrated physiology

    Primary Core Use

    • MMTP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Ducy,  Kousteni, Marks, Mcgraw

  • Korner Judith

    • Irving Assistant Professor of Clinical Medicine

    Affiliation

    • Medicine-Endocrinology

    Expertise

    • Obesity, bariatric surgery

    Research Statement

    My research interests are focused on the hypothalamic regulation of energy homeostasis and the development of treatments for diabetes usign insight gained from bariatric surgery. I am interested in the molecular mechanisms by which several hormones discovered over the past few years control food intake. I am studying the neuroendocrine changes that occur with weight loss in both rodent models and obese humans. I also study the role of agouti-related protein (AGRP) in regulating food intake. AGRP is a hypothalamic peptide that increases food intake in rodents by antagonizing the action of alpha- melanocyte stimulating hormone (a-MSH), a peptide that acts to decrease food intake, at melanocortin receptors within the brain.§ Examining the role of the dopaminergic system in energy homeostasis and insulin sensitivity. My lab also uses rodent models to design effective weight loss strategies for future use in humans. One such study involves combination treatment with naloxone (an opioid antagonist) and leptin (a peptide hormone produces by adipocytes). Our human studies include: (1) Analysis of hormones involved in energy homeostasis before and  after bariatric surgery (gastric bypass and banding) and implantation of a gastric pacemaker, an experimental procedure used for weight reduction; (2) Exploration of different therapies for the treatment of hypothalamic obesity. I have been supported by a DRC PF study that was crucial to obtain R01 funding for my projects. I actively use several Core services.

    Interest Group

    Integrated physiology

    Primary Core Use

    • TBAC

    Secondary Core Use

    • N/A

    Key Collaborations

    Haeusler, Leibel, Wardlaw, Rosenbaum, Zhang, Chung, Goland

  • Kousteni Stavroula

    • Professor of Physiology and Cellular Biophysics

    Affiliation

    • Physiology/CellBiophysics

    Expertise

    • Bone diesease

    Research Statement

    The purpose of Kousteni laboratory is to understand the influence of the skeleton on various physiological processes and in disease. The long term goal is to uncover the pathogenesis of degenerative diseases and to suggest novel and adapted therapies for them. Along these lines we are examining the role of osteoblasts in hematopoiesis with particular emphasis in myelodysplasia (MDS) and acute myeloid leukemia (AML) and studying the function of bone as an endocrine organ regulating glucose metabolism and energy homeostasis.

  • Kuo (Diana) Taiyi

    • Assistant Professor of Medical Sciences

    Affiliation

    • Medicine - Endocrinology

    Research Statement

    The goal of Dr. Kuo’s research is to elucidate the molecular mechanism(s) underlying pancreatic beta cell failure. Her current projects focus on the identification of genes responsible for Type 2 diabetes, leveraging mouse and human genetics and epigenetics. Her studies encompass investigation of basic biological processes and approaches to potential therapeutic intervention, by incorporating molecular biology, biochemistry, genomics, epigenomics, and physiology. She identified C2cd4a as a potential effector of beta cell dysfunction, from integrated analysis of histone modifications and RNA-seq, as well as FoxO1 and Pol2 ChIP-seq, using pancreatic beta cell-specific FoxO1 knockout mice that showed beta cell failure. Her contributions include the observation that genetic ablation of C2cd4a in beta cells of mice phenocopies the metabolic abnormalities of human carriers of VPS13C-C2CD4A-C2CD4B -linked, Type 2 diabetes-associated polymorphisms, resulting in impaired insulin secretion during glucose tolerance tests as well as hyperglycemic clamps. C2cd4a regulates glycolytic genes, and notably represses lactate dehydrogenase and aldolase B, two key beta cell “disallowed” genes. These data suggest a role of C2cd4a in carbohydrate metabolism and cell fate determination. She will continue to examine the role of C2cd4a, and explore its potential as a therapeutic target. She will continue to use all DRC Cores.

    Interest Group

    • Beta cell function and replacement

    Primary Core Use

    • CCSC

    Secondary Core Use

    • ATPI, TBAC

    Key Collaborations

    Alonso, McGraw, Qiang, Chen

  • Laferrere Blandine

    • Professor of Clinical Medicine

    Affiliation

    • Medicine-Endocrinology, Columbia University

    Expertise

    • Obesity, bariatric surgery

    Research Statement

    The focus of my current research, with ongoing funding from the NIH and the ADA, is the mechanisms of diabetes remission and appetite regulation after bariatric surgery, with a  particular interest on the incretin hormones GLP-1 and GIP, and other gut peptides such as PYY- 3-36 and oxyntomodulin.  My laboratory has contributed significantly to the understanding of the mechanisms of diabetes remission after bariatric surgery by showing a normalization of the incretin effect on insulin secretion shortly after GBP. By using a study design of a carefully matched weight loss, we have shown that GBP is superior to diet or gastric banding in terms of incretin levels and effect, insulin secretion and glucose control, and amino acids metabolism. By contributing to the understanding of diabetes remission after bairatric surgery, and the role of the gut in glucose metabolism, we hope to develop new innovative therapeutic intervention to treat type 2 diabetes. As an endocrinologist diabetologist, I treat patients with diabetes type 1 and type 2, with and without obesity. I have been a recipient of DRC PF funds, and I maintain an active involvement with the DRC, especially through my co-leadership of Core B.

    Interest Group

    Global Health, Health Disparities, and Underserved Urban Populations

    Primary Core Use

    • ASSAY

    Secondary Core Use

    • N/A

    Key Collaborations

    Egli, Leduc, Leibel, Rosenbaum, Reilly, Goland, Zhang

  • Lin Qiao

    • Associate Professor

    Affiliation

    • Mechanical Engineering

    Expertise

    • Glucose monitoring devices

    Research Statement

    Qiao Lin's research centers on micro/nanotechnologies as applied to biological sensing and manipulation, with an emphasis on controlling, sensing and characterizing biological systems by integrating microelectromechanical systems (MEMS) transducers with microfluidics. Such systems aim to allow sensitive and accurate analysis of biological systems in well-controlled micro- and nanoscale environments, thereby enabling new insights into fundamental biological phenomena and innovative capabilities for practical biomedical applications. In collaboration with Dr. Milan Stojanovic, The PI will seek to establish methods to sense glucoe concentrations in biologicla fluids, and to design glucose-sensitive insulin molecules. The PI is a past PF recipient. He went on to obtain two separate NIH grants to pursue his work.

    Interest Group

    Beta cell function and replacement, Integrated physiology

    Primary Core Use

    • MMTP

    Secondary Core Use

    • TBAC

    Key Collaborations

    Leibel, Stojanovic, Egli, Doege, Goland, Luchsinger

  • Lo James

    • Assistant Professor of Medicine

    Affiliation

    • Medicine - Cardiology, Cornell

    Expertise

    • Beta cell biology

    Research Statement

    I am a physician-scientist at Weill Cornell Medical College heading a lab in the Metabolic Health Center investigating the fundamental mechanisms of cardiometabolic diseases. We aim to address key questions in cell, molecular and developmental biology while using metabolism as a model system. I have made key contributions by identifying a molecular link between inflammation and dyslipidemia. More recently I have identified a factor that helps to explain the link between obesity and pancreatic beta cell dysfunction in type 2 diabetes. The lab focuses on understanding the molecular regulators of adipose biology and function, pancreatic beta cell physiology, and interactions at the interface of inflammation and metabolic diseases. I was recently awarded a PF from the DRC. This award will be critical to establish my laboratory.

    Interest Group

    Beta cell function and replacement

    Primary Core Use

    • ATPI

    Secondary Core Use

    • MMTP

    Key Collaborations

    Accili, Mcgraw, Qiang, Egli, Doege

  • Luchsinger Jose

    • Associate Professor

    Affiliation

    • Medicine-General Medicine

    Expertise

    • Diabetes and cognitive dysfunction

    Research Statement

    I have served as Director of the Northern Manhattan Center of Excellence in Minority Health and Health Disparities since 2009. Diabetes is the most important disease that we are trying to diagnose, prevent, and treat in this cohort of underserved urban minorities. I began my research career with a minority supplement award, a foundation career development award (New York Academy of Medicine), and a K08 mentored clinician researcher award from NIA (K08 AG20856).  I was a project leader in a P01 grant (AG07232), in the current P60 (P60 MD000206), and was a co-investigator in an Epidemiology and Biostatistics Core of  the P01 award. I have an R01 award from NIA (RO1 AG026413), an equivalent grant from the American Diabetes Association (7-08-CR-41), and I am the leader of the neurocognitive reading center of the landmark Diabetes Prevention Program Outcomes study (2U01DK048404) in which I oversee training of staff and QA/QC activities in 26 sites in the USA. I was a member of the Scientific Advisory Board of the Irving Institute for Clinical Translational Research from 2007 to 2010 (1 UL1 RR024156-01).My interest in diabetes in intertwined with my interest in clinical outcomes in ethnically diverse, disadvantaged populations in the Northern Manhattan Community study, and in my work on insulin resistance and cognitive dysfunction. I have greatly enjoyed the opportunity to work with DRC faculty. I have used the full DRC technical and intellectual resources to obtain preliminary data for a study of the impact of metformin on cognitive function in an at-rick elderly population. And much of my thinking in this are has been affected by the exchanges and interaction with DRC faculty, including Drs. Accili, Ginsberg,  Shea, and Pi-Sunyer.

    Interest Group

    Global Health, Health Disparities, and Underserved Urban Populations

    Primary Core Use

    • TBAC

    Secondary Core Use

    • N/A

    Key Collaborations

    Accili, Ginsberg,  Shea, ad Pi-Sunyer

  • Makarem Nour

    Affiliation

    • Mailman School of Public Health - Epidemiology

    Research Statement

    Dr. Makarem is an epidemiologist with an interdisciplinary research program in cardiovascular, sleep, and nutritional epidemiology. Her research investigates multi-dimensional sleep patterns in relation to cardiometabolic risk. She has shown that sleep is related to maintenance of CVH and that the addition of multidimensional sleep as an eighth metric of CVH would lower CVD risk. In parallel, she investigates timing, regularity, and periodicity of lifestyle behaviors in the 24-h day and across days, assessed using sensors and wearable technologies, in relation to ambulatory blood pressure monitoring and continuous glucose monitoring outcomes. As PI of an American Heart Association (AHA) Soter Collaborative Grant, using data from the Hispanic Community Health Study and through recruiting a new cohort from our catchment community, she has shown that circadian timing of eating is related to hypertension and type 2 diabetes risk in Latinx adults. Her work also provided evidence that variable eating patterns and eating jetlag are associated with adiposity and higher levels of blood pressure and glycemic control indicators. She is currently PI of grants that evaluate sleep patterns and behavioral circadian rhythms in relation to cardiometabolic risk. The NHLBI award examines the circadian rhythm of restactivity patterns, an innovative behavioral measure of circadian rhythmicity in the free-living setting. The AHA award investigates associations of sleep patterns and behavioral circadian rhythms with type 2 diabetes and prediabetes risk as well as with glycemic control indicators and glycemic variability from continuous glucose monitoring. She is also examining the influence of these behavioral rhythms on epigenetic mechanisms related to aging and cardiometabolic disease. She participates in a NIMHD P50 COMMUNITY grant, focused on reducing health disparities in cardiometabolic risk in Latinx adults. She has utilized the TBAC consultative services, begun a collaboration with P&F recipient Dr. Bogun, and plans to use TBAC and contribute to <nm2968@cumc.columbia.edu>Enrichment Program activities.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • TBAC

    Key Collaborations

    St.Onge, Bogun, LaFerrère, Gangwisch

     

  • Mamykina Lena

    • Professor of Epidemiology

    Affiliation

    • Mailman School of Public Health - Epidemiology

    Research Statement

    Dr. Mamykina is an Associate Professor in the Department of Biomedical Informatics at Columbia University. She has a background in Computer Science, Human-Computer Interaction, and Biomedical Informatics. Her research interests include individual and collective sensemaking, problem-solving, and decisionmaking in the context of health self-management and care. Her research uses qualitative methods to study human practices that evolve around health, healthcare and health management. She uses participatory design methods to identify new opportunities to introduce computing and information technologies to facilitate both personal health management and delivery of healthcare. She has experience designing and managing randomized controlled trials evaluating efficacy of novel informatics interventions for improved health. Specific projects of relevance to the DRC include development and evaluation of informatics interventions for personalized coaching in type 2 diabetes with conversational agents, generating personalized nutritional recommendations using computational analysis of data collected with self-monitoring in type 2 diabetes, developing tools to promote observational nutritional learning within online health communities, developing new approaches to supporting clinical decision with patient-generated data, and developing novel tools for communication and information sharing among members of interdisciplinary clinical teams. To this end, she has relied on consultative and assay services from TBAC, and from Enrichment Program activities to advertise her work with the clinical faculty. She’s working closely with P&F recipient Bogun, Core Director Laferrère, and DRC PI, Accili.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • TBAC

    Key Collaborations

    Accili, Bogun, Hripcsak, Goland

  • Marks Andrew

    • Clyde and Helen Wu Professor of Molecular Cardiology

    Affiliation

    • Physiology & Cellular Biophysics

    Expertise

    • Ryanodine receptors

    Research Statement

    The Marks lab is devoted to improving basic understandings of mechanisms that regulate calcium dependent signals including muscle contraction and cell growth. In particular the lab focuses on the structure/function relationships of ion channel macromolecular complexes including the ryanodine receptor/ calcium release channel (RyR) and the IP3 receptor. The lab employs a wide range of techniques including molecular and cell biology, confocal calcium imaging, structural biology, muscle physiology, and generates genetically altered animal models of human diseases to test hypotheses. This approach is responsible for the first drug eluting stent used to prevent coronary artery stent restenosis, and for a first-of-its-kind treatment for heart failure. Dr. Marks has extensively collaborated with DRC members Accili, Leibel, Goldberg, Tall, and Tabas, to understand basic signal transduction pathways by rapamycin, as well as the molecular basis for rapamycin resistance in diabetic patients that receive rapamycin-eluting stents. In his capacity as PI of a NHLBI training grant on basic cardiology, he is also a mentor to several trainees in the DRC who are interested in the interface between heart disease and diabetes, and a consultant to Core facilities and to the DRC leaders as a member of the DRC Internal Advisory Committee. more recently, his interests have included the role of ryanodine receptors in beta cell and insulin secretion. In this regard, he has also mentored a now K99 awardee, Dr. Gaetano Santulli.

    Interest Group

    Beta cell function and replacement, Integrated physiology

    Primary Core Use

    • MMTP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Santulli, Ferrante, Karsenty, Tabas, Accili, Tall, Ginsberg

  • McGraw Timothy

    • Professor of Cell Biology

    Affiliation

    • Cell Biology, Cornell University

    Expertise

    • Glucose transport

    Research Statement

    My lab studies insulin action in adipocytes, including its regulation of the trafficking of the GLUT4 glucose transporter, a process critical for control of blood glucose levels.  In addition, my studies metabolic alterations in turmor stroma cells, exploring the hypothesis that cells of the tumor microenvironment provide metabolic support for cancer cells. Obesity and insulin resistance are main risk factors for many cancers, although the mechanisms linking metabolic dysregulation and cancer are not understood.  Our work on the metabolism of stroma cells is therefore relevant to diabetes research. I have been fortunate to be a recipient of a DRC-sponsored ARRA PF project to do work outside my usual area of expertise, in which we try to idnetify the molecular signature of cancer metbaolism using primary tumor cells from patients undergoing treatment at Cornell Medical Center. The work have not been completed yet, but we are preparing manuscripts and grant applications based on the findings.

    Interest Group

    Integrated physiology

    Primary Core Use

    • MMTP

    Secondary Core Use

    • TBAC

    Key Collaborations

    Accili, Tabas, Karsenty

  • McKimpson Wendy

    • Associate Research Scientist

    Affiliation

    • Medicine - Endocrinology

    Research Statement

    Dr. McKimpson is a junior faculty in the Division of Endocrinology at Columbia University Irving Medical Center with a keen interest in deciphering fundamental
    signaling mechanisms and their roles in human disease, especially during metabolic stress and diabetes. Her current research investigates pancreatic β- cells and hepatocytes, are altered during diabetes and obesity. She was named a Berrie Fellow in Diabetes Research (1/2019) and was awarded a Mentored Research Scientist Development K01 award from the National Institutes of Health (7/2019). Her current research builds on her previous experience in pancreatic beta-cell and gastric biology to investigate insulin-producing cells in the itnestine. Her research goal is to understand basic cellular pathologies in diabetes. She has made extensive use of all DRC Cores and participated in its Enrichment Program, as well as mentored several students. She plans to continue her involvement with the DRC.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • CCSC

    Secondary Core Use

    • MMFP, TBAC

    Key Collaborations

    Yan, Kuo, Colecraft

  • Mendelsohn Cathy

    • Associate Professor of Genetics

    Affiliation

    • Genetics and Development

    Expertise

    • Retinoids in islet cell differentiation

    Research Statement

    We are working on a project looking at the roll of retinoids in islet cell differentiation during development.The long-term goal is to understand the genetic pathways that are important for b- cell formation and to investigate how islet cell progenitors are regulated.  Retinoids are important in IPS and ES cell cultures for differentiation of Pdx1 progenitors toward islet cell lineages, suggesting that Retinoic acid may normally be important for regulating progenitor differentiation. We have inhibited retinoid signaling in Pdx1 progenitors by expressing a dominant negative RA- receptor. We find that retinoid inhibition results in reduced numbers of insulin-expressing cells and increased numbers of glucagon-expressing cells. These studies will enable us to identify genetic pathways that regulate islet and beta cell formation, that may be useful for generating beta-cells in vitro that can be used in treating patients with diabetes.

    Interest Group

    Pancreas Development, B-Cell Function, And Cellular Replacement Therapies

    Primary Core Use

    • MMTP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Blaner, Accili, Sussel

  • Miller Gary

    • Professor of Epidemiology

    Affiliation

    • Mailman School of Public Health - Epidemiology

    Research Statement

    Dr. Miller’s role on this application is center member and Director of the Exposomics/Metabolomics core that provides access to DRC members through TBAC. He began to work on the exposome in 2010 to provide –omic scale measurement of environmental influences on health and disease. Since that time he founded and directed the first NIH center on the exposome, authored the first book on the topic, served as an advisor to several international groups, and developed innovative training programs. The HERCULES Center developed a highthroughput and cost-effective approach to measure hundreds of environmental chemicals, tens of thousands of biological metabolites, and more than 200,000 currently unidentified features. They are replicating this system within the Irving Institute at Columbia University, which includes liquid chromatography and gas chromatography-based Thermo Q-Exactive Oribtrap mass spectrometry. With partners in the U.S. and across the world Dr. Miller leads a Global Exposome Harmonization Project to optimize workflows and standard operating procedures to make the high-throughput analysis of thousands of environmental chemicals consistent and reliable. At Columbia, he leads a new consolidated training program in environmental health and data sciences. His laboratory currently studies environmental drivers of neurodegeneration. He has also developed a platform for high throughput screening of toxicants that disrupt neurotransmitter storage, developed a Parkinson’s disease (PD) mouse model with low expression of the vesicular monoamine transporter (VMAT2), and discovered a role for the synaptic vesicle glycoprotein in dopamine regulation and PD. He has also established a platform to study environmental determinants of aging and cognitive function in C. elegans using high-resolution metabolomics and exposomics.

    Interest Group

    • Genetics and Immunology of T1D

    Primary Core Use

    • TBAC

    Key Collaborations

    Laferrère, Reilly

  • Momen-Heravi Fatemeh

    • Associate Professor

    Affiliation

    • Dental School

    Research Statement

    Dr. Momen-Heravi studies the role of microRNA in disease pathogenesis and aims to harness microRNAs to treat human disease. She studied microRNA signaling and the role of exosomes/extracellular vesicles in the pathogenesis of various diseases for the past 7 years using molecular biology, microRNA signaling, and immunology in different disease models such as alcoholic hepatitis, hepatitis C, head and neck cancer, colorectal cancer, and glioblastoma. She identified the role of exosomes and miR-122 in the pathogenesis of alcoholic liver disease and hepatitis C and investigated the role of miR-155 in monocyte/macrophage signaling. She has also studied the role of microRNAs in head and neck cancer, and elucidated their roles in signaling events in different immune cells’ function. She contributed to current knowledge of exosome isolation and characterization techniques, identified and optimized the methods for exosome-mediated nucleic-acid deliveries (RNAi, microRNA-inhibitors, and microRNA-mimics), conducted immunologic studies to understand microRNAs’ effect on the immune system, and performed in vivo experiments for understanding the tissue/organ distribution of microRNAs and exosomes/extracellular vesicles. She si funded to study the role of monocytes and macrophage signaling through exosomes in the pathogenesis of diabetic periodontopathy. She plans to use TBAC, CCSC, and ATPI and to participate in Enrichment Program activities.

    Interest Group

    • Diabetes dyslipidemia heart disease

    Primary Core Use

    • TBAC

    Key Collaborations

    Ferrante, Laferrère

  • Oberfield Sharon

    • Professor of Pediatrics

    Affiliation

    • Pediatrics

    Research Statement

    Dr. Oberfiled is Professor of Pediatrics and have been Division Director of Pediatric Endocrinology, Diabetes, and Metabolism at Columbia University Medical Center since 2004. Since 2005 she has been the PI of the NIDDK T32 training grant in Pediatric Endocrinology. She has been engaged in patientoriented research for almost 40 years with a focus on disorders of adrenal hormone synthesis, adrenarche and PCOS. She has conducted studies of obesity, insulin resistance, and body composition in children and adolescents. She work closely with the Columbia Center for Children’s Environmental Health on research related to obesity, pubertal development and PCOS in women exposed to environmental endocrine disruptors. She been funded by the NIH, foundations, and industry since 1999. She served on the Subcommittee of the NIDDK National Review Committee (2015-2019). Since 1998 she has mentored 33 postdoctoral fellows and strudents under T35 awards. Graduates of the T32 Training Program have obtained academic leadership and/or research positions in the field of pediatric endocrinology, underscoring the academic focus and rigor of the training program. Indeed, the graduates of this program are engaged in broad areas associated with obesity, diabetes, and pediatric endocrinology. To this end, her interaction with the DRC is essential, since most of her trainees work in DRC laboratories. In addition she is deeply involved as a lecturer and mentor in the DRC Enrichment Program. She intends to continue to do so.

    Interest Group

    • Global health and disparities

    Key Collaborations

    Gallagher, Laferrère, Ferrante

  • Ozcan Lale

    • Assistant Professor of Medical Sciences

    Affiliation

    • Medicine-Molecular Med

    Expertise

    • Hepatic insulin action and Calmodulin Kinase

    Research Statement

    My earlier work elucidated a glucagon/endoplasmic reticulum stress pathway activated in obese liver, whose inhibition safely improves  hyperglycemia and insulin resistance in mouse models of obesity. Targeting an upstream molecule in the pathway in obese mice using a small organic compound has substantial metabolic benefit in a manner that is mechanistically "on-target" and, importantly, is additive with the current leading type 2 diabetes drug, metformin.  These studies led me to be awarded with two independent career development grants from American Heart Association and American Diabetes Association and also appeared as important publications in Cell Metabolism, Diabetes and Cell Reports, suggesting new targets for drug development in the area of type 2 diabetes.
    My current independent research focuses on mechanisms identifying the relationship(s) between insulin resistance and dyslipidemia, and investigations into exploring novel pathways that regulate adipose tissue biology in the setting of obesity.  I have an R01 from NIDDK and a research grant from Pfizer to support my studies on metabolic diseases and dyslipidemia, and I have strong collaborations with two experts in the above areas.  Thus, as a recently promoted tenure-track Assistant Professor and an early stage investigator, I have all the necessary resources needed for me to successfully accomplish this project. 

    Interest Group

    Integrated physiology >

    Primary Core Use

    • MMTP

    Secondary Core Use

    • CCS

    Key Collaborations

    Accili, Ferrante, Pajvani, Tabas, Tall, Haeusler, Leibel, Welch, Ginsberg

  • Pajvani Utpal

    • Assistant Professor of Medicine

    Affiliation

    • Medicine- Endocrinology

    Expertise

    • Notch, insulin signaling and NASH

    Research Statement

    I am an early-career physician-scientist, interested in uncoupling obesity from its metabolic complications, by the discovery of novel, pharmacologically tractable pathways in the development and potential treatment of Type 2 Diabetes (T2D), non-alcoholic fatty liver/steatohepatitis (NAFLD/NASH) and dyslipidemia. This interest stems from both my clinical work with patients with T2D at the Naomi Berrie Diabetes Center at Columbia University, as well as over 15 years of basic and translational research to understand how obesity induces metabolic disease. During my graduate training with Philipp Scherer, we studied the role of adipocytes in regulation of whole-body glucose and lipid homeostasis through secretion of adiponectin. My subsequent post-doctoral work with Mimmo Accili was centered on integrative metabolism in liver, in how nutrient flux is regulated at the hormonal level and affected through cellular cross-talk.
    Although my clinical and laboratory training is in metabolic diseases, my work intersects fields of development, metabolism and cancer biology, by study of the Notch signaling pathway. The Notch family of transmembrane receptors has been traditionally thought to regulate normal development and then remain quiescent unless deregulated in cancer. Contrary to this notion, we found that Notch activity in liver is modulated by both physiologic (fasting/refeeding) and pathologic (insulin resistance) cues in mouse models of obesity. Further, genetic or pharmacologic inhibition of hepatocyte Notch activity abrogates obesity-induced glucose intolerance, and also somewhat unexpectedly, steatohepatitis and liver fibrosis, while mice with hepatocyte-specific Notch gain-of-function show exacerbated phenotypes. These remarkable data prompted a clinical survey in patients, which showed positive correlation between Notch activity and markers of insulin resistance and hepatic triglyceride content, but independent and strongest associations with biochemical and pathologic markers of NASH. We are now taking a bench-to-bedside approach, through collaborative efforts with a multi-disciplinary team of physician-scientists who care for patients with liver disease.

    Interest Group

    Integrated physiology 

    Primary Core Use

    • MMTP

    Secondary Core Use

    • CCS

    Key Collaborations

    Accili, Ginsberg, Leibel, Marks, Ozcan, Qiang, Lavine

  • Qiang Li

    • Assistant Professor

    Affiliation

    • Pathology and Cell Biology

    Expertise

    • Pathology & Cell Biology Adipose tissue in Diabetes

    Research Statement

    My research delves into the adipose remodeling, the mechanism of nuclear receptor PPARγ activation, and the protein posttranslational modifications (PTMs) in regulating metabolic homeostasis. I have expertise in basic molecular mechanistic studies and integrated physiology of obesity, diabetes and their comorbidities including cardiovascular diseases and cancer. I have extensive experience identifying PTMs on important metabolic regulators, including PPARγ, FoxO1, CREB, p53 and Raptor, and investigating how PTMs fine-tune their activity. Since I started my laboratory in January, 2016, I have been actively interacting with my DRC colleagues and collaborators. As a result, I have published my first senior author paper. The PF has been extraordinarily helpful to jumpstart a new project related to treating diabetes with non-TZD Ppar agonists.

    Interest Group

    Integrated physiology

    Primary Core Use

    • MMTP

    Secondary Core Use

    • CCS

    Key Collaborations

    Accili, Welch, Pajvani, Ginsberg, Tall, Tabas, Ozcan

  • Reilly Muredach

    • Professor of Medicine

    Affiliation

    • Medicine - Cardiology

    Expertise

    • Medicine - Cardiology

    Research Statement

    I am a cardiologist and Professor of Medicine at Columbia University, relocated from the University of Pennsylvania. I have expertise in clinical cardiovascular medicine, human genetics and functional genomics, clinical pharmacology, epidemiology and mechanistic translational research. In 2016, I relocated to Columbia from University of Pennsylvania. My Cardiometabolic Research Program is dedicated to translational and genomic studies and focuses on (1) novel mechanisms of human atherosclerosis underlying recent GWAS discoveries in human, (2) the role on innate immunity in promoting cardio-metabolic disease, (3) the functions of adipose tissue inflammation in insulin resistance and atherosclerotic risk, and (4) genomic and transcriptomic discovery in human cardio-metabolic disorders. My group employs a translational precision medicine approach including human functional genomics, human induced pluripotent stem cell (hiPSC) technology and gene editing, animal based mechanistic studies, patient-oriented interrogation as well as large scale epidemiological studies. I have a track record in mentoring, collaborating, assembling and overseeing multidisciplinary teams for execution of translational, genomic and laboratory heart disease research. At Columbia, as Director-designate of the Irving Institute for Clinical and Translational Research, home of Columbia Clinical and Translational Science Award (CTSA), I will also build and extend programs in clinical and translational research as well as in genomics and precision medicine while continuing my research program in cardio-metabolic diseases. 

    Interest Group

    Diabetes dyslipidemia heart disease

    Primary Core Use

    • TBAC

    Secondary Core Use

    • N/A

    Key Collaborations

    Ginsberg, Tall, Korner, Laferrere, Luchsinger, Marks, Chung

  • Reyes-Soffer Gissette

    • Assistant Professor of Medicine

    Affiliation

    • Medicine- Molecular Medicine

    Research Statement

    Dr. Reyes-Soffer studies the metabolic pathways that regulate lipid and lipoprotein metabolism in humans with a focus on lipoprotein(a), a causal risk factor for atherosclerotic cardiovascular disease. She has a growing research portfolio from NIH and leading industry-sponsored studies. In addition to Lp(a), she has collaborations to examine lipid metabolism of rare lipid mutations, with published work on the RX19 APOC3 and pending publications on studies of TM6Sf2 and APOC2 mutations in humans . She has extensive experience in the design of human clinical studies and the use of highly specific and innovative laboratory methods to analyze the secretion and clearance of isotope-labeled proteins isolated from human blood. Globally there are less than five laboratories actively using these methods highlighting their importance to describe the mechanisms that regulate lipid and lipoproteins and their risk to cardiovascular and other disease. Specific to the current proposal, she has used TBAC for stable isotope turnover studies and has contributed to developing new analytical tools for this capability. She plans to continue her utilization of TBAC and involvement in the Enrichment Program.

    Interest Group

    • Diabetes and dyslipidemia heart disease

    Primary Core Use

    • TBAC

    Secondary Core Use

    • ATPI

    Key Collaborations

    Haeusler, Tabas, Tall, Ginsberg, Reilly

     

  • Rosenbaum Michael

    • Professor of Clinical Medicine

    Affiliation

    • Pediatrics

    Expertise

    • Childhood obesity

    Research Statement

    I foster collaborative research in the prevention of type 2 diabetes in children and the development of an understanding of body weight regulation in adults. I am the Principal Investigator in a large multi-site study of the effects of school-based intervention on clinical, behavioral, and biochemical risk factors for adiposity-related co- morbidities and Co-Prinicipal Investigator in studies of the behavioral and neuronal aspects of feeding behavior in adults. Specifically, our initial studies of body weight regulation examined energy output relative to body composition in lean and obese subjects following weight perturbation. Based on preliminary data demonstrating a metabolic “opposition” to reduced weight maintenance, we then expanded to include autonomic and neuroendocrine function as well as studies of whole body skeletal muscle ergometry.  We found that reduced weight maintenance was associated with significant increases in skeletal muscle work efficiency, delayed satiation, and changes in functional magnetic resonance imaging studies of subject responses to food that are consistent with observed delay in satiation and other alterations in energy intake behavior that occur as the result of weight loss. Our school-based studies of the pathophysiology and prevention of adiposity-related co-morbidities in children represent a multi- site project studying a multi-ethnic population of over 800 students. I have been the PI for this project, entitled Reduce Obesity and Diabetes (ROAD), and have supervised and participated directly in recruitment, administration, teaching (middle school students and physicians), laboratory, data analyses, and overall supervision of this project from its inception. This project has been an excellent training ground for young clinical investigators and has currently resulted in approximately 8 publications and over 30 abstract presentations, most of which have pediatric endocrine fellows as first authors. I have also mentored 2 junior faculty through internal research grants who have gone on to receive K awards on which I was also a mentor. Currently, I am working a total of 12 pediatric endocrine fellows on the ROAD project and 3 masters degree students who are doing their theses with me on the effects of exercise on skeletal muscle. I plan to continue working with co-investigators and to foster junior investigators through the DERC.

    Interest Group

    Integrated physiology, global health, health disparities, and underserved urban populations

    Primary Core Use

    • TBAC

    Secondary Core Use

    • N/A

    Key Collaborations

    Demmer, Desvarieux, Leibel, Wardlaw, Korner, Laferrere, Ginberg

  • Rubin Mishaela

    • Associate Professor

    Affiliation

    • Medicine - Endocrinology

    Research Statement

    Dr. Rubin, as a member of the Columbia Diabetes Research Center, will conduct clinical research in metabolic bone diseases, investigating the structural and material alterations in the skeleton of type 1 and type 2 diabetes patients. She is currently completing an NIH sponsored clinical trial to investigate the skeletal effects of blocking advanced glycation endproduct accumulation in postmenopausal women with type 2 diabetes. She is also a co-investigator in the Skeletal Health study of the long-term DCCT/EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) study of type 1 diabetes patients. In addition, she leads an NIH funded study characterizing the longitudinal changes in bone microarchitecture of type 1 diabetes children as they undergo peak bone accrual. She plans to utilize TBAC and participate in Enrichment Program activities as a lecturer and mentor.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • TBAC

    Key Collaborations

    Kousteni, Page-Wilson, Laferrère

  • Rumora Amy

    • Assistant Professor of Neurology

    Affiliation

    • Department of Neurology

    Research Statement

    Dr. Rumora aims to identify the specific molecular mechanisms that lead to peripheral neuropathy in diabetes and reverse nerve damage with MUFA supplementation. She recently discovered that SFAs and MUFAs differentially regulate sphingolipid levels within the peripheral nerves of murine models of prediabetes. Mice fed an SFA-rich diet have significant increases in peripheral nerve ceramides correlating with PN phenotypes. Conversely, mice switched from an SFA-rich diet to a MUFA-rich diet showed significant increases in both ceramides and complex sphingolipids associated with improvements in nerve function. She is trying to pinpoint the specific lipid metabolic pathways that modulate nerve function in response to SFAs and MUFAs in prediabetic murine models. Her background in biochemistry, mitochondrial biology, and murine models of prediabetic neuropathy make her uniquely suited to identify molecular mechanisms that regulate peripheral neuropathy. She is a new faculty at Columbia and a new DRC member. She plans to utilize MMFP, ATPI, and TBAC, apply to P&F grants, and participate in Enrichment Program activities.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • CCSC

    Secondary Core Use

    • MMFP, TBAC

    Key Collaborations

    Haeusler, Choi

  • Sachs David

    • Professor of Medicine

    Affiliation

    • Medicine-Immunology

    Research Statement

    Dr. Sachs is Professor of Medical Sciences and Surgical Sciences at Columbia University and Professor of Surgery Emeritus at Harvard Medical School and Massachusetts General Hospital. He has worked consistently at the interface between basic research and clinical applications in the field of transplantation for more than 30 years and has been responsible for developing an inbred miniature swine model used in studies related to diabetes. He plans to utilize DRC Cores, especially CCSC, and to participate in its Enrichment Program as a lecturer and mentor, as well as to collaborate with other immunologists in the program.

    Interest Group

    • Genetics and Immunology of T1D

    Primary Core Use

    • CCSC

    Secondary Core Use

    • TBAC

    Key Collaborations

    Griesemer, Chen, Sykes, Egli, Yamada

     

  • Saleheen Danish

    • Professor of Medicine

    Affiliation

    • Medicine - Cardiology

    Research Statement

    Dr. Saleheen is an Associate Professor & Director Global Genomics at the Department of Medicine and Cardiology at the Columbia University. He is the PI of the Pakistan Genomic Resource (PGR) and the founding director of the Center for Non-Communicable Diseases, Pakistan. His research team has already enrolled more than 150,000 participants on whom extensive lifestyle information and biological samples have been collected. This biological resource includes approximately 40,000 participants with heart attacks, 6,000 patients with imaging-confirmed stroke, 25,000 patients with type-2 diabetes, 20,000 patients with heart failure and 40,000 healthy participants. PGR is being rapidly expanded to include 1 million participants. In the next phase of expansion, they are capturing other outcomes, including chronic kidney disease, non-alcoholic fatty liver disease, Rheumatoid Arthritis, SLE, Parkinson’s disease, Movement disorders, Age Related Macular degeneration and many others. A distinguishing feature of this population is that 40% of the participants are born of unions between first cousins. He is leveraging the high levels of consanguinity to identify null homozygotes (i.e., human knockouts). These human knockouts are being systematically evaluated through deep phenotyping studies. Additionally, his conducts whole-exome sequencing studies in > 200,000 participants and whole-genome sequencing studies in 10,000 participants. He is interested in leveraging DRC resources to find collaborators to characterize human knockouts resulting in diabetes, and will make use primarily of TBAC and ATPI, in addition to participating in the Enrichment Program.

    Interest Group

    • Genetics and Immunology of T1D

    Primary Core Use

    • CCSC

    Secondary Core Use

    • TBAC

    Key Collaborations

    Tabas, Reilly, Thaker

  • Shapiro Lawrence

    • Professor of Biochemistry and Molecular Biophysics

    Affiliation

    • Ophtalmology 

    Research Statement

    Dr. Shapiro has made his most important contributions in understanding the structural biology of hormones such as resistin and adiponectin, determined by Xray crystallography, an area which requires significant expertise with proteins. His diabetes work has focused on protein identification by mass spectrometry and has expanded into comparative proteomics using differential in-gel electrophoresis techniques. His work has also led to the determination of the structure of AMPK. He has been involved in DRC activities from the outset and has led a Core facility for nearly nine years. He plans to continue his involvement with the DRC, which is critical to translate his basic structural findings into clinically useful information. To this end, he will continue to participate in Enrichment Program activities and serve as a consultant to DRC faculty members on matters of structural protein biology.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • ATPI

    Key Collaborations

    Leibel, Lin

  • Schwabe Robert

    • Professor of Medicine

    Affiliation

    Medicine - Cardiology

    Research Statement

    Dr. Schwabe’s research has investigated mechanisms that promote the progression of chronic liver disease, focusing on the development of liver injury, inflammation and fibrosis in earlier stages and recently increasingly on the role of fibrosis in the development of liver cancer in later stages. With the steep increase of obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) is affecting almost one quarter of the global adult population (1.5 billion people) and has already become the main cause for advanced liver disease in many places. Notably, chronic liver disease kills more than 2 million people per year world-wide, and fibrosis is the main determinant of mortality. The laboratory has studied the biology of hepatic stellate cells (HSC) and liver cancer for over 15 years. Besides defining key fibrogenic pathways such as TLR4, CCR1, and CCR5, his laboratory has contributed several fundamental key findings, including demonstrating of the ability of HSC to revert to an inactive phenotype; demonstration that HSC contribute 85-95% of fibrogenic cells in the liver; demonstration of a key role for the microbiota in the development of fibrosis and hepatocellular carcinoma (HCC). In the last five years, these efforts have largely shifted to understanding the function of HSC in NAFLD and non-alcoholicassociated steatohepatitis (NASH) in disease progression and the development of HCC. As a DRC member, he has collaborated with the Pajvani and Tabas labs to understand how diabetes and metabolic changes affects HSC and their interaction with hepatocytes. He is also collaborating with DRC member Califano to understand transcriptional regulation and cell-cell communication, focusing on human NASH. He plans to continue to use most DRC Cores and to be involved in the Enrichment Program.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • MMFP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Tall, Ginsberg, Tabas, Pajvani

  • St-Onge Marie-Pierre

    • Associate Professor of Nutritional Medicine

    Affiliation

    • Medicine- Endocrinology

    Expertise

    • Energy balance, dietary and behavioral interventions

    Research Statement

    The overall focus of Dr. St-Onge’s research is the study of the impact of various small dietary and behavioral changes on energy balance. Her main research interests include the study of lifestyle behaviors for body weight control and cardiovascular disease prevention. This includes examining the effects of functional foods or beverages and food components for weight management and cardiovascular disease risk prevention. Another major component of her research involves the study of the relationship between sleep and weight management and disease risk. Methods employed in Dr. St-Onge’s lab include indirect calorimetry (energy expenditure); magnetic resonance imaging, dual energy X-ray absorptiometry, and computed tomography (body composition); and functional magnetic resonance imaging (neuronal networks involved in appetite regulation).

    Interest Group

    Integrated physiology

    Primary Core Use

    • TBAC

    Secondary Core Use

    • N/A

    Key Collaborations

    Pi-Sunyer, Laferrere, Kissileff, Gallagher, Leibel, Rosenbaum

  • Stojanovic Milan

    • Associate Professor of Medical Sciences

    Affiliation

    • Experimental therapeutics

    Expertise

    • Theranostic devices

    Research Statement

    My primary research interest is in the construction of autonomous therapeutic and diagnostic molecular devices based on nucleic acids.We have five related projects in our laboratory: (1) decision-making by molecules in solution; (2) development of molecular sensors; (3) recognition- triggered drug release; (4) movement of catalytic nanoassemblies on recognition surfaces; (5) development of the oligonucleotide-based zip codes for tissue-specific delivery. I have been involved with the DRC to apply my knowledge to the development of glucose sensors.

    Interest Group

    Beta cell function and replacement

    Primary Core Use

    • CCS

    Secondary Core Use

    • TBAC

    Key Collaborations

    Lin, Harris

  • Suh Yousin

    • Charles and Marie Robertson Professor of Obstetrics & Gynecology

    Affiliation

    • Departments of Ob/Gyn and Genetics

    Research Statement 

    Dr. Suh utilizes a diverse array of state-of-the-art functional genomics tools to identify (epi)genetic factors that contribute to aging. Aging is the single largest risk-factor for most complex human disease, including type 2 diabetes and is emerging as a major component in basic, translational and clinical research. To gain further insight into the (epi)genetic link between aging and disease, she focuses on the identification of functional sequence and epigenetic variation in human populations and the assessment of their potential functional impact on aging-related phenotypes. This should ultimately result in an integrated approach to study the connection between disease and aging at different levels, i.e., from genetic and epigenetic determinants in the form of genetic and epigenetic variants, through cell type- and tissue-specific regulated gene expression, to molecular and cellular endpoints in the tissues. Ultimately, this should lead to new targets for interventions as well as (epi)genetic markers for aging and its associated diseases. She is the Charles and Marie Robertson Professor of Reproductive Sciences in Ob/Gyn and Professor of Genetics in Genetics/Development and leads a new Program on Reproductive Aging and Women’s Health, focusing on how functional (epi)genetic variants influence aging and aging-related diseases in women. She is an active member of the Columbia Diabetes Research Center. Recently, she received an R01 from NIDDK, focused on the identification and characterization of functional variants associated with T1D in close collaboration with Dr. Egli. She is also the recipient of a P&F grant focused on functional T2D variants, a new interest for the Suh lab with no external funding. The support from the pilot grant will expedite our efforts in characterizing T2D GWAS variants, moving from genetic association to function and will provide preliminary data for an R01 grant.

    Interest Group

    • Beta cell function and replacement

    Primary Core Use

    • ATPI, MMFP

    Secondary Core Use

    • CCSC

    Key Collaborations

    Karsenty, Kousteni, Leibel

     

  • Sykes Megan

    • Director, Columbia Center for Translational Immunology

    Affiliation

    • Medicine, Immunology

    Expertise

    • Transplant tolerance

    Research Statement

    Our research is in the areas of hematopoietic cell transplantation, achievement of graft-versus- leukemia effects without GVHD, organ allograft tolerance induction and xenotransplantation.My research program aims to utilize bone marrow transplantation as immunotherapy to achieve graft- versus-tumor effects while avoiding the common complication of such transplants, graft-versus- host disease. Our laboratory studies in this area have led to novel approaches that have been evaluated in clinical trials. Another major area has been to utilize bone marrow transplantation for the induction of transplantation tolerance, both to organs from the same species (allografts) and from other species (xenografts). Our laboratory has worked toward the development of clinically feasible, non-toxic methods of re-educating the T cell, B cell and NK cell components of the immune system to accept allografts and xenografts without requiring long-term immunosuppressive therapy. Our work has also extended into the area of xenogeneic thymic transplantation as an approach to tolerance induction, and into the mechanisms by which non- myeloablative induction of mixed chimerism reverses the autoimmunity of Type 1 diabetes.

    Interest Group

    Beta cell function and replacement

    Primary Core Use

    • CCS

    Secondary Core Use

    • ATPI

    Key Collaborations

    Goland, Christiano, Sussel, Egli, Creusot

  • Tabas Ira

    • Richard J. Stock Professor of Medicine Immunology

    Affiliation

    • Medicine-Molecular Medicine

    Expertise

    • Inflammation and atherosclerosis

    Research Statement

    I direct a basic and translational research laboratory studying the cellular and molecular basis of interaction between atherosclerosis and diabetes. In recent years, our diabetes-related interests have evolved to include studies of atherosclerotic plaque progression in diabetes models, and studies of the mechanism of calcium-dependent regulation of hepatic glucose production. With regard to plaque studies, we have focused on mechanisms of plaque necrosis focused on ER stress-induced macrophage apoptosis and defective efferocytosis. Moreover, we have studied physiologic, cellular, and molecular links to obesity and insulin resistance related to both macrophage apoptosis and liver-derived metabolic disturbances and dyslipidemia. We have developed tools to interrogate in-depth molecular and cellular mechanisms using cultured primary macrophages and primary hepatocytes and to test relevance and causation in vivo through the use of genetically altered mice, including the Cre-lox conditional knockout system. My laboratory has worked in the lesional macrophage field for >15 years and has gained a high level of conceptual and technical expertise in this area. With support from the Columbia DRC, we have made the transition to liver studies, and we are poised to make a contribution to this important area of public health.

    Interest Group

    Diabetes, Dyslipidemia, And Heart Disease

    Primary Core Use

    • CCS

    Secondary Core Use

    • MMTP

    Key Collaborations

    Accili, Ozcan, Ferrante, Tall, Ginsberg

  • Tall Alan

    • Tilden-Weger-Bieler Professor of Medicine

    Affiliation

    • Medicine-Molecular Medicine

    Expertise

    • Lipoproteins, atherosclerosis

    Research Statement

    The laboratory is carrying out research on the molecular mechanisms responsible for human diseases. The approach is to use molecular, genomic and cellular approaches to investigate basic aspects of the pathogenesis of atherosclerosis. A major focus is on molecular mechanisms of cellular cholesterol efflux, mediated by the interaction of extracellular apoA-I with the lipid transporter ABCA1. We are carrying out studies on the transcriptional regulation of ABCA1 gene expression, and regulation of the degradation of ABCA1 protein. This has led to the elucidation of a class of transcription factors (LXRs) that co-ordinately regulate cellular cholesterol efflux and reverse cholesterol transport. We nejoy extensive interactions with DRC members Accili, Ferrante, Ginsberg, Deckelbaum, Goldberg, Tabas, Welch, and others. We use many Core facilities, participate in the enrichment program, and intend to continue to do so.

    Interest Group

    Diabetes, Dyslipidemia, And Heart Disease

    Primary Core Use

    • CCS

    Secondary Core Use

    • MMTP

    Key Collaborations

    Welch, Tabas, Accili, Goldberg, Ginsberg, Ganda

  • Thaker Vidhu

    • Assistant Professor of Pediatrics

    Affiliation

    • Pediatrics

    Research Statement

    Dr. Thaker is an endocrinologist trained in bioinformatics and molecular biology, interested in studying mechanisms affecting body weight regulation. During her fellowship training in Pediatric Endocrinology, she initiated the Genetics of Early Childhood Obesity (GECO) study. She has recruited children with syndromic and non-syndromic forms of severe early onset obesity for both sequencing and genotyping, focusing on children from racial and ethnic minorities where the genetic architecture is less well known than those of European ancestry. She has identified novel variants in known genes and prioritized 3 novel genes for the weight regulation pathway. After joining the Division of Molecular Genetics at Columbia University, she has embarked on the functional studies of these gene and gene variants. She has established patient-specific induced pluripotent stem cell (iPSC) lines and their isogenic controls to identify the perturbed networks and pathways in phenotype specific cell-types. In the current DRC proposal, she has used the TBAC and MMFP and will continue to do so. The metabolomics subcore of TBAC was essential to advance her studies. She has applied for P&F funding and plans to resubmit the application after revision.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • CCSC

    Secondary Core Use

    • ATPI

    Key Collaborations

    Leibel, Doege, Saleheen

  • Vunjak-Novakovic Gordana

    • University Professor

    Affiliation

    • Mechanical Engineering

    Research Statement

    Dr. Vunjak-Novakovic’s Laboratory for Stem Cells and Tissue Engineering is focused on tissue engineering approaches to improving human health. They  investigate innovative technologies for engineering human tissues – including bone, cartilage, heart, and lung – by an integrated use of stem cells, biomaterials, and bioreactors. The long-term goals are to develop effective treatment modalities for regenerative medicine, tissue models for stem cell research and study of disease, and “organs-on-a-chip” platforms for use in precision medicine. They direct human cell differentiation and assembly into functional tissues using a “cell-instructive” approach based on tissue-specific scaffolds (providing a template for tissue formation) and advanced bioreactors (providing environmental control, molecular and physical signaling). The biological principles of our designs and the implementation of physical factors are key for unlocking the biological potential of the cells. In the bone, access to nutrients and in particular oxygen, and exposure to hydrodynamic shear associated with interstitial flow and dynamic compression are critical for its development and function. In the heart, mechanical stretch is induced by electrical signals, and the orderly electromechanical coupling is crucial for the heart development and function. In the lung, the function is governed by ventilation and blood flow, providing local and convective transport, and mechanical stretch. Their work has been reported in 415 peer-reviewed research articles, in journals including Nature, Cell, Nature Biotechnology, Nature Medicine, Nature Biomedical Engineering, Nature Communications, Nature Protocols, PNAS, Cell Stem Cell, Science Advances, iScience and Science Translational Medicine , that have been cited over 56,000 times (h=132). She is actively collaborating with Drs. Egli, Creusot, and Sykes to develop an islet-on-achip model to mimic vascular flow interactions with endocrine cells. She has received P&F funding as an established investigator new to diabetes, and plans to continue to use DRC Cores.

    Interest Group 

    • Beta cell function and replacement

    Primary Core Use

    • CCSC

    Secondary Core Use

    • MMFP

    Key Collaborations

    Doege, Egli, Leibel

  • Wardlaw Sharon

    • Atkins Professor of Medicine

    Affiliation

    • Medicine-Endocrinology

    Expertise

    • Neuroendocrinology

    Research Statement

    We study the hypothalamic regulation of energy homeostasis. This project focuses on the melanocortin neuropeptide system which plays a key role in regulating appetite and body weight and is an important target for leptin in the hypothalamus. Studies center on the regulation of proopiomelanocortin (POMC) and the POMC-derived peptides, a-MSH, g-MSH and ß-EP, together with the newly discovered agouti related protein (AGRP). Ongoing studies are examining the regulation of POMC and AGRP gene expression, peptide processing and peptide release in the rat hypothalamus by both leptin and insulin as well as interactions between the POMC and AGRP neurons themselves which both express melanocortin receptors. The role of leptin in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis is also being studied. The HPA axis plays a key role in energy homeostasis and is intricately related to the obesity syndromes in leptin deficient animals. Transgenic mice which overexpress a-MSH and g-MSH have also been developed to further understand the role that these neuropeptides play in modulating feeding behavior, metabolic and endocrine responses. Current studies are focusing on the modulation of peripheral insulin sensitivity by the hypothalamic melanocortin system.

    Interest Group

    Integrated physiology

    Primary Core Use

    • MMTP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Accili, Rosenbaum, Leibel, Egli, Chung

  • Welch Carrie

    • Assistant Professor of Medical Sciences

    Affiliation

    • Medicine-Molecular Medicine

    Expertise

    • Genetics of complex disorders, atherosclerosis

    Research Statement

    Acute complications of atherosclerosis greatly impact morbidity in Western civilizations, especially intertwined with diabetes. We are using a variety of mouse genetics approaches to identify new genes and pathways involved in atherosclerosis. In collaboration with Drs. Accili, Tall and Tabas, we are investigating the role of insulin resistance in atherogenesis. In an independent study, we identified a novel atherosclerosis susceptibility locus on chromosome 4 that overlaps the region of homology with a widely-replicated human CAD susceptibility locus on chromosome 9p21. We have demonstrated that haplo-insufficiency of a candidate disease gene residing in the locus, Cdkn2a (an inhibitor of cell proliferation), results in accelerated atherosclerosis. Gene expression of Cdkn2a is down-regulated in macrophages, an important cell mediator of atherosclerotic lesion development, and results in increased cell proliferation. It will be of interest to determine whether the diabetic condition intensifies this effect.

    Interest Group

    Diabetes, Dyslipidemia, And Heart Disease

    Primary Core Use

    • MMTP

    Secondary Core Use

    • CCSI

    Key Collaborations

    Accili, Tall, Tabas, Chung, Pajvani, Ozcan

  • Weisberg Stuart

    • Assistant Professor of Medical Sciences

    Affiliation

    • Medicine - General Medicine

    Research Statement

    Dr. Weisberg’s laboratory at Columbia University Irving Medical Center focuses on the study of tissue immunity, and the role of macrophages in shaping protective and pathologic tissue immune responses within specialized tissue microenvironments. As an MD/PhD student, he was the first author of a classic JCI paper on macrophage infiltration of adipose tissue that spawned a new field of research and has been cited over 10,000 times. He has now completed a detailed analysis of T cells and macrophages in human pancreas through integrated use of multiparameter flow cytometry, RNAseq, quantitative multiplex immunofluorescence and functional studies of the primary pancreatic immune cells in co-culture. These studies revealed predominant T lymphocyte and macrophage populations that exhibit distinct features of tissue residence and pancreas-specific molecular signatures. he also defined functional interactions between pancreatic T-lymphocytes and macrophages that help maintain pancreatic immune homeostasis. Ongoing studies focus on defining how cross talk between macrophages and T cells controls immune responses within pancreas, and how metabolic stressors such as obesity alters these immune cell interactions and contributes to organ dysfunction and disease. He has used and plans to continue to use most DRC Cores, primarily CCSC and ATPI.

    Interest Group

    • Beta cell function and replacement

    Primary Core Use

    • CCSC

    Secondary Core Use

    • ATPI

    Key Collaborations

    Creusot, Sykes, Griesemer, Accili

  • Yamada Kazuhiko

    • Assistant Professor of Medicine

    Affiliation

    • Medicine - Immunology

    Research Statement

    Dr. Yamada is Professor of Surgical Science in Surgery and Director, Surgical Research, Columbia Center for Translational Immunology (CCTI). He has a broad background in transplantation immunology, as well as in transplant surgery. He has conducted both allogeneic and xenogeneic transplantation projects. He has investigated mechanisms of transplant tolerance in pre-clinical large animal models and developed innovative strategies for the induction of tolerance across both allogeneic and xenogeneic barriers in large animal translational research models. He has performed over 1,000 cases of allogeneic and xenogeneic kidney, thymus, islet and heart transplantation in both miniature swine and non-human primates. More specifically, he has studied the role of the thymus and vascularization of cells/tissue in the induction of tolerance and developed innovative composite vascularized organs known as thymo-kidneys and isletkidneys. Dr. Yamada participates in DRC activities related to tolerance induction in Type 1 Diabetes, has used CCSC and plans to continue to do so, in addition to collaborating with other immunologists.

    Interest Group

    • Genetics and Immunology of T1D

    Primary Core Use

    • CCSC

    Secondary Core Use

    • MMFP, TBAC

    Key Collaborations

    Sachs, Griesemer, Chen, Sykes, Egli, Creusot

  • Yan Kelley

    • Assistant Professor of Medicine

    Affiliation

    • Medicine - Gastroenterology

    Research Statement

    Dr. Yan is a physician-scientist trained in gastroenterology, structural biology, and stem cell biology. This background provides her with a unique perspective and opportunity to study intestinal epithelial stem cell (ISC) biology at the molecular, cellular, and tissue levels. Her PhD research aimed to understand how 3D molecular structure enables biological function to confer specificity in proteinprotein or protein-nucleic acid interactions. Specifically, she has experimentally examined these interactions in signal transduction pathways important in cancer, including ligand/receptor interactions, using structural biology, biochemistry and biophysics. She is also a practicing clinical gastroenterologist with clinical interests in the field of stem cell biology and regenerative medicine. She has conducted research in ISC biology and used mouse genetics, in vivo models, ex vivo 3D organoid culture models, and single-cell genomics to examine stem cell fate decisions. She discovered functional differences among ISC populations identified by different markers highlighting that different cell types participate in tissue regeneration under different biological contexts. She has participated in the NIH Intestinal Stem Cell Consortium since its inception, and published multiple papers with members of the consortium, including as lead author on a study using comparative transcriptomics to profile putative ISCs identified by various markers. These studies have highlighted the plasticity of enteroendocrine lineage cells to regain developmental potential and regenerate the intestinal epithelium following injury. She has also investigated Wnt signaling regulation of ISC populations in colorectal cancer using novel structural biology and biochemical approaches to perturb this pathway in vivo . She is now pursuing a thorough characterization of enteroendocrine cells for which has leveraged her involvement in the DRC through collaborations with Accili, Kuo, Egli and others, as well as utilization of CCSC and ATPI Cores. She plans to continue these important interactions.

    Interest Group 

    • Integrated physiology

    Primary Core Use

    • CCSC

    Secondary Core Use

    • MMFP

    Key Collaborations

    McKimpson, Kuo, Colecraft

  • Zeltser Lori

    • Associate Professor of Pathology and Cell Biology

    Affiliation

    • Department of Pathology

    Research Statement

    Dr. Zeltser’s current research is focused on defining the metabolic impact of developmental processes during gestation and the post-weaning period in mice (corresponding to early gestation and early childhood in humans). These alterations can predispose to diabetes in later life, as shown in patients with a history of maternal GDM. Her longstanding research interests are in understanding the molecular basis for the specification of cell identities and neuronal connectivity in the developing central nervous system, and how perturbations in these developmental processes affect physiological functions. Her graduate and postdoctoral studies focused on defining developmental processes in the mouse and chick that direct the acquisition of cell identities in the diencephalon, the embryonic precursor to the thalamus and hypothalamus. Her laboratory focuses on characterizing two distinct developmental processes that could, in principle, impart persistent influences on metabolic phenotypes: (1) the specification of functionally distinct neuronal populations in the embryonic hypothalamus, and (2) the establishment of defended set-points for phenotypes related to adiposity and energy expenditure during the post-weaning period in rodents. She plays a key role in the DRC as Director of ATPI, and is actively engaged in Enrichment Program activities.

    Interest Group

    • Integrated physiology

    Primary Core Use

    • ATPI, MMFP

    Secondary Core Use

    • CCSC, TBAC

    Key Collaborations

    Emiliano, Leibel, Zhang, Zuker

  • Zhang Hanrui

    • Associate Research Scientist

    Affiliation

    • Medicine - Cardiology

    Research Statement

    Dr. Hanrui Zhang is interested in the characterization and utilization of human induced pluripotent stem cell (iPSC)-derived macrophages and endothelial cell as human physiology-relevant cell models to study human metabolic diseases such as diabetes. To this end, she employs high-resolution transcriptomic profiling and functional interrogation of human macrophage non-coding transcriptome during inflammatory and alternative polarization, as well as CRISPR/Cas-mediated gene knock-outs and knock-ins to elucidate human macrophage-specific functions. She has been awarded a R00 from NIDDK that has catalyzed interactions with the DRC research faculty and DRC Core utilization. She plans to continue her involvement to meet the goals of her R00 research.

    Interest Group

    • Diabetes dyslipidemia heart disease

    Primary Core Use

    • ATPI

    Secondary Core Use

    • MMFP

    Key Collaborations

    Doege, Egli, Leibel

  • Zhang Yiying

    • Research Scientist

    Affiliation

    • Pediatrics-Molecular Genetics

    Expertise

    • Obesity, fat cell biology

    Research Statement

    We are interested in the regulation of LEPR trafficking and signaling by bioactive lipid molecules and cytokines. Impaired leptin signaling is an important contributor to the impaired energy homeostasis and glucose metabolism in obesity.  Cell surface expression of the leptin receptor (LEPR) is tightly regulated and is an important determinant of leptin signaling activity. We have shown that TNF-alpha and bioactive lipids, including ceramide and cholesterol, have profound effects on cell surface expression level and signaling activity of LEPR. The focus of their current studies is to delineate the molecular mechanisms by which these molecules regulate LEPR trafficking and signaling. This work is of possible relevance to the studies being pursued with regard to the roles of the primary cilium in leptin signaling and to cellular mechanism of leptin resistance.

    Interest Group

    Integrated physiology

    Primary Core Use

    • MMTP

    Secondary Core Use

    • CCS

    Key Collaborations

    Leibel, Small, Qiang, Ferrante, Chung, Rosenbaum, Accili

  • Zuker Charles

    • Professor of Biochemistry and Molecular Biophysics

    Affiliation

    • Department of Biochemistry

    Expertise

    • Taste receptors

    Research Statement

    We use a combined molecular, genetic, and physiological approach to study signal processing, information transfer, and coding mechanisms in sensory systems, in particular photoreceptors, mechanoreceptors, and taste receptors. My interest in DRC activities is to investigate the role of taste recpetors in metabolic regulation. To this end, I plan to have extensive interactions with DRC faculty and to utilize the four Cores.

    Interest Group

    Integrated physiology

    Primary Core Use

    • MMTP

    Secondary Core Use

    • ATPI

    Key Collaborations

    Leibel, Egli, Doege