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chait-20111

Alan Chait, M.D.

Division Head
Edwin L. Bierman Professor of Medicine

Alan Chait, M.D. has had a long-standing interest in plasma lipid metabolism and in the cell biology of atherosclerosis, with particular emphasis on the role of nutrition, diabetes, and inflammation in atherogenesis. His laboratory uses in vitro approaches and mouse models to dissect out the complex interactions amongst inflammation, obesity, diabetes, dyslipidemia and atherosclerosis.

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John J. Albers, Ph.D.

Research Professor of Medicine
Research Director, Northwest Lipid Metabolism and Diabetes Research Laboratories

Dr. Albers research interests include elucidation of the role of proteins of lipid transport in lipid and lipoprotein metabolism. The role of lipid transport proteins in pathophysiology of the central nervous system disorders. Pathophysiology of lipid transport in subjects with genetic hyperlipidemia and premature vascular disease.

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Denis G. Baskin, Ph.D

Research Professor of Medicine and Biological Structure

My research program focuses on the CNS regulation of food intake, body weight, and energy balance by hormones such as insulin and leptin. These hormones, which are present in blood in direct proportion to body fat mass, have profound anorexic effects when they enter the brain, where they alter the transcription, synthesis, and secretion of peptides (such as neuropeptide Y and melanocortins) in feeding-related neural circuits of the hypothalamus and brainstem.

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J. Ernie Blevins, Ph.D.

Research Associate Professor of Medicine

Current research interests include brain pathways regulating leptin signaling from the hypothalamus to the brainstem linked to the control of food intake, neuroanatomical techniques-for mapping neural circuits (oxytocin, corticotropin releasing hormone) involved with mediating the effects of leptin on food intake and energy expenditure, and histochemical methods (immunocytochemistry and in situ hybridization) for detecting the expression of neural genes involved in the regulation of energy homeostasis.

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Karin Bornfeldt, Ph.D.

Professor, Departments of Medicine and Pathology
Associate Director, Diabetes & Obesity Center of Excellence

Cellular and molecular mechanisms of diabetes-accelerated atherosclerosis. People with diabetes have an increased risk of developing cardiovascular complications caused by atherosclerosis, such as myocardial infarction, stroke and peripheral vascular disease. We use animal models and isolated vascular cells to investigate the processes that mediate diabetes-accelerated atherosclerosis. Projects range from in vivo studies to intracellular transduction studies.

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William J. Bremner, M.D., Ph.D.

Department of Medicine Chair
Robert G. Petersdorf Professor of Medicine

Mechanisms for central nervous system control of pituitary gonadotropin secretion and the effects of gonadotropins on gonadal function. Major physiological and clinical questions being addressed include: (1) Can a safe, effective, reversible contraceptive for men be developed? (2) What are the effects of aging on the male reproductive endocrine system? (3) What are the effects of androgens in men and women? (4) What are the relative roles of LH and FSH in controlling testicular function?

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John D. Brunzell, M.D.

Professor Emeritus of Medicine

Genetic abnormalities in lipoprotein metabolism. Specific interest in: (1) the pathophysiological and molecular defects in familial combined hyperlipidemia; (2) the role of hepatic lipase gene and activity in determination of dyslipidemia seen in the metabolic syndrome with intraabdominal obesity and insulin resistance in diabetes and at menopause.

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Vincenzo Cirulli, M.D., Ph.D.

Associate Professor of Medicine

The overall objective of Dr. Cirulli’s research work is to understand mechanisms of islet cell development and function, with special emphasis on the role of cell-cell and cell-matrix adhesion receptors as instructive cues for developing islet progenitors. In an effort to develop strategies of possible translational value to human diseases, his research makes use of both, animal models and human ES and iPS cells.

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Laura Crisa, PhD

Associate Professor of Medicine

Immune recognition of major hystocompatibility (MHC) antigens on tissue transplants is the primary barrier to allografts acceptance. There are, however, certain Class I MHC antigens that can trigger regulatory immune responses. This is the case of human HLA-G. There is extremely low polymorphism of HLA-G in the human population and high expression levels of this molecule on the trophoblast, the fetal tissue at the maternal-fetal interface, has been shown to be involved in the down-regulation of cytotoxic NK and T cell immune responses.

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David E. Cummings, M.D.

Professor of Medicine

Neuroendocrine mechanisms regulating appetite, body weight, and glucose homeostasis. Specific areas of study include the following: 1) Characterizing roles of the orexigenic hormone ghrelin in energy balance and glucose homeostasis; 2) Clarifying hormonal mechanisms that contribute to weight loss and diabetes resolution after bariatric surgery; and 3) Understanding the interplay between homeostatic and hedonic pathways in the regulation of food intake.

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Laura den Hartigh, Ph.D.

Research Assistant Professor of Medicine

The prevalence of obesity and associated diseases is rapidly reaching epidemic proportions. Representing the major cellular constituent of adipose tissue, adipocytes are now regarded as prominent players in the metabolic as well as hormonal regulation of adiposity. Despite the fundamental role adipose tissue plays in whole body metabolism, nutritive mechanisms that contribute to its maintenance in the context of obesity remain poorly understood. Dr. den Hartigh’s research focuses on the effects of nutrient excess on cellular metabolism, with particular attention given to the effects of fatty acids on cell types associated with the development of obesity such as adipocytes and monocytes/macrophages.

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Anthony DeSantis, M.D.

Clinical Associate Professor of Medicine

Dr. DeSantis specializes in Endocrinology focusing on type 1 and type 2 diabetes, adrenal problems, metabolic bone disease, pituitary problems and thyroid problems.

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Cora Espina, MN, ARNP, CWCN

MN, ARNP, CWCN

Together with physician colleagues, manage patients on the Hyperglycemia Consult Service, who are hospitalized at the University of Washington Medical Center. Following their initially discharge from the hospital, oversee and support patients transition to outpatient clinic. This clinic is aimed at supporting the continuum of care following discharge.

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Alan Failor, M.D.

Clinical Professor of Medicine

Dr. Failor specializes in Endocrinology focusing on Diabetes, Diabetes care and Pituitary Disorders.

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Karen E. Foster-Schubert, M.D.

Associate Professor of Medicine

Dr. Foster-Schubert’s research focus is on human obesity and body weight regulation. She has investigated the role of exercise-induced weight loss and macronutrient effects on the orexigenic hormone ghrelin, as well as ghrelin’s effects on islet insulin release. Current research projects are aimed at the following: 1) hormonal and physiologic predictors (including alterations in adipose gene expression) of successful weight loss maintenance following diet and exercise interventions; 2) the effect of varying dietary energy density on body weight regulatory hormones and appetite; 3) development of a novel imaging method to measure parameters of hypothalamic regulation of body weight in humans, using a multi-disciplinary approach.

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Christiane Hampe, Ph.D.

Research Associate Professor of Medicine

My research interests are the dissection of the role of autoantibodies to the 65kDa isoform of glutamate decarboxylase (GAD65) (GAD65Ab) in the pathogenesis of type 1 diabetes. GAD65Ab are found in 70-80% of newly diagnosed type 1 diabetes patients. While these autoantibodies are widely accepted as markers for the disease, preliminary data indicate that disease-specific GAD65Ab modulate T-cell responses. It is of great importance to understand the effect of GAD65Ab on processing and presentation of GAD65. The central hypothesis is that autoantibody modulation of T cell mediated autoimmunity plays a key role in the pathogenesis of type 1 diabetes.

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Chang Yeop Han, Ph.D.

Research Assistant Professor of Medicine

Dr. Han's research focuses on the adipose tissue inflammation in obesity. Obesity is characterized by adipocyte hypertrophy and accumulation of macrophages in adipose tissue. Both adipocytes and macrophages secrete a number of pro-inflammatory molecules, which may lead to insulin resistance, systemic inflammation and cardiovascular disease. He is especially interested in how adipocytes produce chemotactic factors to recruit monocytes and extracellular matrix molecules to increase the adhesion of macrophages by nutrient excess such as excess glucose and various free fatty acids. He is studying potential mechanisms involved in reactive oxygen species, interaction between NFKB and PPAR, Toll-like receptor and NADPH oxidase at hypertrophic adipocyte. He is also studying how adipocytes cross-talk with macrophage to determine the phenotype of macrophage in obesity.

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Wei Hao, M.D., Ph.D.

Clinical Associate Professor of Medicine
Director, Inpatient Hyperglycemia Consult Service at UWMC

Development and oversight of a hospital-wide inpatient hyperglycemia consult service at UWMC, leading a team of ARNP, fellows and residents, and ensuing safe transitions between the inpatient and outpatient setting for patients with diabetes and hyperglycemia; development of systems to improve glycemic management within UWMC with a goal to meet hospital quality measures.
In Endocrine care, I have special interest in management of multiple endocrine neoplasia syndromes and parathyroid disorders. I have a long-standing research interest in the pathogenesis, prevention and intervention of type 1 diabetes.

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Jay W. Heinecke, M.D.

Professor of Medicine

Jay Heinecke, M.D., is a Professor in the Department of Medicine and a member of the Molecular and Cellular Biology Graduate Program. He holds the Karasinski Chair in Metabolic Research and serves as Director of the Mass Spectrometry Resource (Department of Medicine).

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Elaine D. Henley, M.D.

Clinical Professor of Medicine

Past research primarily involved the study of carbohydrate metabolism with emphasis on diabetes, insulin and hypoglycemic agents. Current activities are clinically-oriented with wide general endocrine interests in the evaluation, diagnosis, and treatment of patients with all endocrine diseases. Special interests are young adults with thyroid, gonadal, adrenal and pituitary problems.

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Irl B. Hirsch, M.D.

Professor of Medicine

Using new technologies for the management of diabetes, particularly using improved glucose sensors and insulins for both type 1 and type 2 diabetes. I have a long-standing interest in both better management strategies and how these strategies improve outcomes in hyperglycemic inpatients. For this interest we are now studying bone marrow transplant patients. Finally, I have a long-standing interest in how glucose variability may impact the pathogenesis of diabetic vascular complications. We are currently funded to study this in our first randomized trial, "FLAT-SUGAR".

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Rebecca L. Hull, Ph.D.

Research Associate Professor of Medicine

My research focuses on cellular mechanisms underlying islet secretory dysfunction and loss of beta-cell mass in diabetes. Our interest lies not only in beta-cell intrinsic mechanisms of failure, but also how other cell types in the islet modulate beta cell function and dysfunction. We are currently investigating the role of the islet endothelial cell in determining islet function, and studying the composition of the islet extracellular matrix under conditions of health and disease. Our studies utilize a variety of physiology, cell biology and histochemical approaches.

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Steven E. Kahn, M.B., Ch.B.

Professor of Medicine

Assessment of islet function and insulin action in states of normal and abnormal carbohydrate metabolism. Determination of defects in islet function and their relationship to genetic markers in subjects at high risk for developing type 2 diabetes. Evaluations of the mechanisms regulating the synthesis and secretion of islet amyloid polypeptide by the pancreatic ß-cell in vitro and in vivo, and its deposition as islet amyloid. Role of fat distribution on metabolic variables associated with diabetes and cardiovascular disease.

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Renee C. LeBoeuf, Ph.D.

Research Professor of Medicine

Research is directed toward identifying environmental and genetic factors involved in the development of atherosclerosis and diabetes/obesity. In particular, our research focuses on vascular complications associated with type 1 and type 2 diabetes. Environmental factors include dietary components (e.g. fat, cholesterol and carbohydrates). Genetic factors include genes coding for proteins involved in lipid metabolism and inflammation. A focus is the role of tumor necrosis factor (TNF) and mice lacking TNF receptors are used to determine the molecular mechanism(s) controlling disease severity. Inbred mouse strains differing in susceptibility to these diseases are used. Finally, inbred mice are used in positional cloning approaches to identify new genes involved in disease development.

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Santica Marcovina, Ph.D., D.Sc.

Research Professor of Medicine
Director, Northwest Lipid Metabolism and Diabetes Research Laboratories

Structure, metabolism and ethnic differences of lipoprotein(a) or Lp(a). Role of elevated L(a) levels and apo(a) isoform size in coronary artery disease and thrombosis. Clinical studies on diabetes prevention and intervention.

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Gregory Morton, Ph.D.

Research Associate Professor of Medicine

Studies the role of the brain in the regulation of energy balance and glucose metabolism. Research focuses on the action of the adiposity signals insulin and leptin in the hypothalamus and examines the mechanisms and pathways by which they mediate their effects on food intake, body weight and peripheral insulin sensitivity using physiological, molecular biological and histochemical approaches.

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Susan Ott, M.D.

Professor of Medicine

Clinical and bone histomorphometric studies of bone metabolism. Effects of contraception and lifestyle on bone density in adolescents; mineralization density of bone; bone histomorphometry of women with breast cancer; renal osteodystrophy.

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Stephanie Page, M.D., Ph.D.

Associate Professor of Medicine
Section Chief, Endocrinology and Diabetes, Harborview Medical Center

Physiologic and therapeutic properties of androgens and androgen manipulation in humans. Major projects include: 1) examination of the consequences of testosterone replacement on prostate health in middle-aged and elderly, hypogonaldal men at both the clinical, hormonal, and molecular levels; 2) examining the effect of androgens on host immunity and inflammation; and 3) determining the effect of testosterone on cardiovascular risk and risk factors. Continued involvement in projects investigating the pharmokinetics of novel oral formulations of testosterone delivery and the development of an effective, reversible male hormonal contraceptive.

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Jerry P. Palmer, M.D.

Professor of Medicine
Section Head, VA Puget Sound Health Care System
Director, Diabetes Endocrinology Research Center

My research focuses on the immunology of the type 1 diabetes disease process in humans. The dual role of T cells in mediating the beta cell destruction of this disease, but also in mediating protection against beta cell destruction is being investigated. We are participating in TrialNet which is testing the ability of immunomodulatory therapies to preserve beta cell function in recently diagnosed type 1 diabetes patients and the ability to prevent or delay clinical type 1 diabetes in high risk individuals. Approximately 20-30 percent of typical type 2 diabetes patients have anti-islet antibodies similar to type 1 diabetes. We are investigating the genetic, immunologic, and metabolic components of the diabetes disease process in these antibody positive type 2 patients to determine whether this is type 1 diabetes at an older age or a different disease process.

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Mara Roth, MD

Mara Y. Roth, M.D.

Assistant Professor of Medicine

Mechanisms for control of intratesticular steroidogenesis and the effects of gonadotropins and exogenous hormones on gonadal function. Major physiological and clinical questions being addressed include: 1) Why do hormonal contraceptives work for some men, but not others? 2) What are the minimal intratesticular hormones required for spermatogenesis? 3) Can intratesticular steroid concentrations predict male infertility and be used to develop specific therapies?

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Katya Rubinow, M.D.

Assistant Professor of Medicine

My research focus is the role of sex steroid signaling in macrophage biology, specifically in the setting of cardiometabolic disease. Aging in men is characterized by progressive decline in testosterone production, and very low levels of circulating androgens consistently have been associated with increased risk of insulin resistance (IR), type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). Further, IR and T2DM tend to arise prior to CVD in these men and may contribute substantially to cardiovascular risk. Consequently, determining the physiologic effects of testosterone on systemic insulin sensitivity could have clinical relevance to all men as they age and offer novel therapeutic strategies for preventing or delaying diabetes and CVD.

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Michael Schwartz

Michael W. Schwartz, M.D.

Professor of Medicine
Director, Diabetes and Obesity Center of Excellence

Physiological mechanisms underlying body weight regulation and the pathogenesis of obesity and diabetes. Major questions under investigation are: (1) By what mechanism do circulating signals involved in the regulation of body adiposity, including insulin and leptin, act in the brain? (2) Which specific hypothalamic pathways are sensitive to the actions of insulin and leptin, and what is the cellular basis for these actions? (3) What are the behavioral and metabolic consequences of the actions of insulin and leptin on their hypothalamic targets? (4) What mechanism is responsible for hypothalamic resistance to these hormones in obese individuals? (5) Do neurocircuits involved in food intake also regulate insulin action in peripheral tissues?

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Baohai Shao, Ph.D.

Research Assistant Professor of Medicine

HDL – the good form of cholesterol – removes cholesterol from macrophages, which plays a key role in protecting humans from atherosclerosis. However, not all forms of HDL are cardioprotective. Dr. Shao’s research focuses on the impact of oxidative modifications and diabetes on the anti-atherogenic effects of HDL. One major area of interest is myeloperoxidase, a heme enzyme secreted by macrophages. Dr. Shao is also interested in modification of HDL by glucose and reactive carbonyls that can covalently attach to amino acids and damage proteins. His research group uses cell biology together with tandem mass spectrometry to pinpoint specific amino acid residues in HDL that are damaged by reactive intermediates. Another major effort is directed towards developing sensitive mass spectrometric assays to identify novel HDL oxidation products in translational studies. Dr. Shao’s long term goal is to understand the role of oxidative reactions in the pathogenesis of atherosclerosis, diabetes and other inflammatory diseases in humans.

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Savitha Subramanian, M.D.

Assistant Professor of Medicine

Our research focuses on studying the role of inflammation in adipose tissue in obesity using mouse models, such as the LDL receptor deficient mouse, a model of the metabolic syndrome. Using this model we study the impact of components of the metabolic syndrome such as visceral obesity, insulin resistance and inflammation on atherosclerotic cardiovascular disease. We are currently also using this mouse model to study the effects of fat accumulation in the liver (nonalcoholic steatohepatitis) and the role of hepatic inflammation in insulin resistance and cardiovascular disease. A second area of interest is the role of the nutrient sensor molecule mTOR in adipose tissue in obesity. mTOR is important in longevity, a condition associated with improved insulin sensitivity. I am currently involved in studying the role of inhibiting mTOR using mouse models and dietary interventions to study the role of this complex molecule in obesity and insulin resistance.

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Ian Sweet, Ph.D.

Research Associate Professor
Director, Islet Core, UW DERC
Affiliate Investigator, Benaroya Research Institute

Understanding the dual role of mitochondrial energy production in mediating nutrient stimulated insulin secretion system and in maintaining viability of pancreatic beta cells. Methods have been developed to continuously assess oxygen consumption, cytochrome redox state, calcium and NAD(P)H levels in isolated islets concomitantly with insulin secretion. These techniques are being used to examine the bioenergetics of nutrient induced insulin secretion, the mechanisms of calcium mediated insulin secretion, real time kinetics of apoptosis and necrosis, the contribution of compromised islet function to the progression of type 2 diabetes and the acute and chronic effects of GLP-1 on islet function.

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Gerald J. Taborsky, Jr., Ph.D.

Research Professor of Medicine

Role of the autonomic nervous system in mediating the glucagon response to hypoglycemia. Impairments in sympathetic neural pathways in autoimmune diabetes. Contribution of the parasympathetic nervous system to the insulin response to oral glucose.

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Chongren Tang, Ph.D.

Research Assistant Professor of Medicine

Cholesterol accumulation in arterial macrophages and inflammation of the artery wall both contribute to the development of cardiovascular disease (CVD). HDL appears to protect against CVD by several mechanisms that remove cholesterol from arterial cells and suppress inflammation. A major cardioprotective factor associated with HDL metabolism is ATP-binding cassette transporter A1 (ABCA1), a cell membrane protein that exports cholesterol and phospholipids from cells to lipid-depleted HDL apolipoproteins, such as apoA1. My research focuses on studies of biochemical mechanisms and signaling pathways by which ABCA1 functions as cholesterol exporter and anti-inflammation molecule. Another focus of my research is the studies of the effects and mechanisms of diabetes and diabetes associated factors on ABCA1 and ABCG1.

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Joshua Thaler And Chongren Tang, Diabetes & Obesity Center Faculty

Joshua Thaler, M.D., Ph.D.

Assistant Professor of Medicine

My focus is the hypothalamic regulation of energy homeostasis and the alterations to this system during obesity pathogenesis. My primary project investigates hypothalamic inflammation and its relationship to high fat diet-induced weight gain with an emphasis on the role of glial cells (astrocytes and microglia) in modulating the neuronal regulation of energy homeostasis. In particular, we are determining whether glial cells provide a repair response to diet-induced damage to critical hypothalamic neurons and whether interventions targeted at glia may therefore influence the course of obesity. A second study examines the role of inflammatory signaling in hypothalamic neurons and microglia in obesity-associated insulin resistance and diabetes.

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Dace Trence, M.D.

Professor of Medicine
Director, Metabolism, Endocrinology and Nutrition Fellowship Program

Improving health care delivery to patients with diabetes through improved skills of medical residents, nurse practioners, use of electronic and encounter medical record. Osteoporosis and diabetes mellitus.

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Subbulaxmi Trikudanathan, MD, MRCP, MMSc

Clinical Assistant Professor of Medicine

Dr. Subbu Trikudanathan specializes in Endocrinology with particular focus on diabetes, polycystic ovarian syndrome, adrenal disorders, thyroid disorders and metabolic bone disease.

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Tracy Tylee, MD

Clinical Assistant Professor of Medicine

Dr. Tylee specializes in endocrinology, with a particular interest in the management of type 1 and type 2 diabetes, adrenal disorders, disorders of calcium metabolism and thyroid disease, including thyroid biopsies.

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Kristina Utzschneider, M.D.

Associate Professor of Medicine

Dr. Utzschneider's research focuses on the interaction between liver disease and glucose metabolism. One study investigates the effect of iron overload due to hereditary hemochromatosis on insulin sensitivity and beta-cell function. A second study attempts to better understand the mechanisms linking non-alcoholic fatty liver disease and insulin resistance. In addition, she continues to study the relationship between measures of insulin response and insulin sensitivity using measures derived from an oral glucose tolerance test.

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Tomas Vaisar, Ph.D.

Research Associate Professor of Medicine

Dr. Vaisar's research focuses on examining the role of inflammation in the development and progression of cardiovascular disease. Specifically, his research looks at the role lipoproteins in the development of cardiovascular disease. Dr. Vaisar applies state of the art mass spectrometric methods to characterization of HDL and multiplexed MRM based quantitative analysis of all proteins in HDL.

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Simona Vuletic, M.D.

Research Assistant Professor of Medicine

My research interests include metabolism of lipids, lipoproteins and lipid transfer proteins in the brain with an emphasis on neurodegenerative and neuroinflammatory diseases; the role of lipid transfer proteins in inflammation and cardiovascular disease; and basic biology of lipid transfer proteins [in particular phospholipid transfer protein (PLTP)], including their role in signal transduction and intracellular processes, as well as structure-function studies.

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D. Scott Weigle, M.D.

Professor of Medicine

Studies of mechanisms of experimental and human obesity. Identification of factors produced by adipose tissue that influence appetite and fuel metabolism. Effect of dietary macronutrient composition and aging on body fat mass. Alteration in body fat distribution by protease inhibitor therapy in HIV infection. Undergraduate physiology education.

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Brent Wisse, M.D.

Associate Professor of Medicine

The focus of the laboratory is on investigating the central (CNS) mechanisms that lead to diminished appetite (anorexia) in chronic disease states. Anorexia and weight loss are major complications of many chronic diseases including cancer, AIDS, adrenal insufficiency and inflammatory disorders, that lead to an excess morbidity and mortality. The hypothalamic neuropeptides that control appetite are being examined in a variety of rodent models of pathologic anorexia, with particular emphasis on treatments that block melanocortin and cytokine signaling. The long-term goals are to identify targets that may lead to improved treatment of anorexia and of obesity.

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Lorena Alarcon-Casas Wright, MD

Clinical Assistant Professor of Medicine

Dr. Wright’s focus is directed towards glycemic control and glycemic markers in diabetes and pregnancy complicated by diabetes. Prevention of complications related to diabetes and preventing/delaying pre-diabetes and diabetes progression.

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Sakeneh Zraika

Sakeneh Zraika, Ph.D.

Research Assistant Professor of Medicine

Investigating mechanisms of pancreatic beta-cell dysfunction and death in type 2 diabetes. Use of rodent models to study impairment of insulin secretion in the setting of elevated glucose and fat. Emphasis on oxidative stress and derangements in insulin exocytosis. Study of novel aspects of islet amyloid formation, including degradation mechanisms.

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