Interest Groups

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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

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

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(link sends e-mail)>Enrichment Program activities.

Interest Group

• Integrated physiology

Primary Core Use

• TBAC

Key Collaborations

St.Onge, Bogun, LaFerrère, Gangwisch

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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