Training Faculty - Research Preceptors

 

Members of the Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism

Research programs are built around and driven by the interests and activities of the faculty. This section provides a brief description of active research programs available to the trainee. A detailed list of relevant research publications is available via PubMed:

  • George Bakris, M.D., Professor

    Department of Medicine

    Head, ASH Comprehensive Hypertension Center

    gbakris@gmail.com

    Research in the area of hypertension focuses on two dimensions: epidemiology and pathophysiology. Current studies in the area of epidemiology involve a focus on clinical trials and outcomes in African-Americans and those with chronic kidney disease secondary to hypertension or diabetes. Additional, ongoing multi-center trials in resistant and refractory hypertensive patients using novel surgical approaches and devices. He also participated in studies in the recently completed African American Study of Kidney Disease (AASK) trial. Additionally, the Kovler Diabetes Center Database of those with hypertension and diabetes is being explored to assess various trends in clinical practice and there applicability to improve care of diabetes.

    Research Studies:

    • Renal denervation trial - SYMPLICITY HTN-3; National Co-Principal Investigator
    • Development of new potassium binding resin-clinical trial - AMYTHEST; Principal Investigator
    • Effects of Nebivolol, a NO donor, on central aortic pressure and pulmonary function in COPD patients; Principal Investigator
    • Effect of a novel angiotensin receptor blocker on adipose aldosterone levels in obese patients; Principal Investigator
    • Effects of CTP-499 on proteinuria in patients with diabetic nephropathy; Principal Investigator

    Bakris GL PubMed Publications


  • Graeme I. Bell, Ph.D., Louis Block Distinguished Service Professor

    Departments of Medicine, and Human Genetics

    Principal Investigator, Diabetes Research and Training Center

    g-bell@uchicago.edu

    Dr. Bell is a leading authority on the genetics of Diabetes Mellitus. He directs a program to identify genes that cause diabetes and determine how mutations in these genes affects cell function. The program involves close interactions between basic scientists, clinical investigators and physicians, allowing translation of research findings from the bench to the bedside. There are learning opportunities for trainees interested in basic research as well as those interested in clinical investigation and translational research.

    Bell GI PubMed Publications


  • Matthew Brady, Ph.D., Associate Professor

    Department of Medicine

    Vice-Chairman Committee on Molecular Metabolism and Nutrition

    mbrady@medicine.bsd.uchicago.edu

    The overall focus of the lab is metabolic signaling. We are particularly interested in the insulin-mediated regulation of energy storage in adipocytes and hepatocytes, the interplay of glucose and lipid metabolism, the regulation of hepatic glucose production, and the molecular mechanisms underlying the development of insulin resistance in animal models and humans. Research is conducted using cell lines, primary murine hepatocytes and adipocytes, and samples collected from human fat biopsies.

    Adipose tissue plays a central role in the control of systemic energy metabolism. Fat is by far the largest energy depot in the body, and additionally secretes a growing number of endocrine factors that influence feeding behavior and insulin sensitivity in other tissues. Dysregulation of adipocyte function during obesity is a key contributor to the development of insulin resistance and subsequent type 2 diabetes. Over the past 10 years, there have been an increasing number of studies that report a link between decreased sleep duration and/or quality and an increased risk for obesity and diabetes. In collaboration with Drs. Van Cauter, Ehrmann and Tasali in the Department of Medicine at the University of Chicago, we have initiated a series of studies to examine the effects of sleep disruption on insulin sensitivity in primary human adipocytes using cells obtained by subcutaneous needle biopsy. In all studies described below, fat biopsies are obtained before and after the experimental intervention. Insulin sensitivity is assessed by phospho-specific immunoblotting and we also have a series of metabolic assays (lipogenesis, lipolysis, glucose uptake) established for use in human adipocytes. Finally, in more recent experiments with obese subjects, mRNA has been isolated for use in microarray analysis.

    Insulin is the most potent physiological anabolic agent known, promoting the synthesis and storage of carbohydrates and lipids, and inhibiting their degradation and release into the circulation. Currently, there are three main projects in the lab in this area:

    • The first involves studying the impact of altering glycogen metabolism in adipocyte energy sensing and function. Additionally, we are currently generating a PTGfl/fl animal which will be used to tissue specific PTG knockout lines. These animals will then be fully characterized using in vitro and in vivo assays, including the use of metabolic cages.
    • A second project addresses the surprising fact that now seven different proteins have been identified that target PP1 to glycogen particles. The need for multiple proteins that apparently serve the same function and exhibit overlapping tissue distribution remains poorly understood. These studies will be extended in the future through adenoviral administration into mice to modulate these proteins in livers in vivo.
    • A final project is addressing the molecular mechanisms by which environmental endocrine disrupting chemicals (EDCs) exert their effects. EDCs are synthetic pollutants and contaminants that inappropriately activate or inactivate endocrine systems.

    We are also investigating effects of modulating sleep patterns on insulin sensitivity in human adipose tissue. In the first series of experiments, lean, healthy, young subjects were subjected to 4 nights of sleep deprivation. A second group of subjects were subjected to 4 nights of specific disruption of slow-wave sleep. In both instances, there was a marked induction of insulin resistance detected at the cellular level using the primary human adipocytes. The molecular mechanisms by which these changes occur are being investigated.

    In a second study, obese subject with polycystic ovary syndrome (PCOS) will be screened for degree of obstructive sleep apnea (OSA). The hypothesis to be tested in these studies is that restoration of sleep quality though 8 week treatment with continuous positive airway pressure (CPAP) will result in an improvement in insulin resistance and global energy metabolism. In parallel, fat biopsies will be performed and insulin action in primary adipocytes will be assessed as described above. Additionally, mRNA is prepared for gene profiling to elucidate the molecular changes occurring in fat tissue upon improvement in sleep in these subjects.

    Brady PubMed publications


  • Ronald N. Cohen, M.D., Associate Professor

    Department of Medicine

    RonCohen@medicine.bsd.uchicago.edu

    Dr. Cohen is investigating the role of corepressors in the adipocyte and other important endocrine tissues. Nuclear receptors such as the thyroid hormone receptor (TR), retinoic acid receptor (RAR), and peroxisome proliferator-activated receptor gamma (PPARgamma) have the capacity to recruit corepressors in the absence of their respective ligands or in the presence of antagonists. These corepressors, such as SMRT and NCoR, in turn form a complex with histone deacetylase activity in order to decrease gene transcription. Dr. Cohen investigates the mechanisms underlying the specificity of corepressors to distinct nuclear receptor complexes, and has shown that SMRT and NCoR repress the program of adipocyte differentiation. Studies are ongoing to dissect the roles of SMRT and NCoR in mature adipocyte function as well as in adipogenesis.

    Cohen PubMed publications


  • Dianne Deplewski, M.D., Assistant Professor

    Department of Pediatrics

    Program Director, Pediatric Endocrine Training Program

    ddeplews@peds.bsd.uchicago.edu

    Dr. Deplewski is studying the biologic and molecular basis of the growth of the sebaceous gland, using the rat preputial gland as a model. She examines the effects of retinoic acid analogs and androgens on the growth of preputial cells in culture and the effect of the stromal-epithelial interface on the growth and ultrastructure of sebaceous cells in monolayer and lifted-raft culture. She examines the expression of 5-reductase in sebaceous cells the peroxisomal proliferator activated receptors in sebaceous cells, which is a focus of the grant in which she is a co-investigator.

    Future directions of research are to further studies on the role of GH and IGFs in preputial cell growth and development. Specifically, she will attempt to delineate the direct and indirect effect of GH in the sebaceous gland system by utilizing antibodies against IGFs, and by measuring the levels of the IGFs and IGF binding proteins in cell culture media.

    Deplewski PubMed publications 


  • Alexandra Dumitrescu, M.D., Ph.D., Instructor

    Department of Medicine

    adumitre@medicine.bsd.uchicago.edu

    Dr. Dumitrescu's research is focused on the study of the pathophysiology of inherited defects affecting the thyroid function, in particular those involving transmembrane thyroid hormone transport and intracellular thyroid hormone metabolism. One of the defects she studies is that of the X-linked gene MCT8, a transmembrane transporter of thyroid hormone. Its deficiency results in severe psychomotor and development delay in males, also known as Allan Herndon Dudley syndrome. Among known inherited disorders of the thyroid axis in humans, this is the first involving thyroid hormone transport into cells. Dr. Dumitrescu has generated an Mct8 knockout mouse model and extensive in vivo and in vitro work on this mouse model continues to uncover the underlying mechanisms for this complex defect.

    Another novel thyroid defect she studies is that caused by mutations in selenocysteine incorporation sequence binding protein 2 (SBP2) and represents the first defect in a component of the selenoprotein synthesis machinery. This deficiency has consequence on growth and thyroid function at young age, cause decreased fertility in males and are expected to result in increased cancer susceptibility in both genders with age. Severe SBP2 gene mutations present additional features, such as congenital myopathy, developmental delay, sensorineural hearing loss and complex immune deficits, that reflect multiple selenoprotein deficiencies. Dr. Dumitrescu's current studies address the need for an in vivo model to further understand the pathophysiology of this new genetic defect, by generating mouse models with Sbp2 deficiency. Initial investigations will uncover the underlying mechanisms for the characteristic thyroid phenotype, infertility, growth delay and myopathy. The study of the aging animals will allow close monitoring for manifestations later in life, and other presumed phenotypes, including cancer, neurodegenerative disorders and immune dysfunction. These investigations are relevant to multiple physiological functions and pathways.

    Research Project:

    • Pathophysiology of the Selenocysteine incorporation defects caused by Sbp2 mutations

    Dumitrescu PubMed publications


  • David A. Ehrmann, M.D., Professor

    Department of Medicine

    Director, University of Chicago Center for PCOS

    Associate Director, University of Chicago Clinical Resources Center (CTSA)

    Director, University of Chicago Ambulatory Care Clinic, Section of Endocrinology, Diabetes, & Metabolism

    dehrmann@medicine.bsd.uchicago.edu

    Metabolic and cardiovascular abnormalities related to sleep disruption are particularly evident in individuals with obstructive sleep apnea (OSA), a disorder most closely associated with risk factors of obesity and male gender. While the prevalence of OSA is higher in men than in women, the failure to recognize OSA by health care professionals is particularly common in women. The traditional explanation has been that women present with a symptom complex that suggests disorders such as depression or insomnia, rather than OSA. Biological explanations for the gender difference in symptomatology have not been studied. Women have been underrepresented in the majority of studies that examined the link between OSA and its adverse metabolic consequences. In addition, it is now clear that the prevalence of OSA in some populations of women far exceeds that of men. The most prominent example is that of women with polycystic ovary syndrome (PCOS), itself the most common hormonal disorder in women. Recent studies, as well as Dr. Ehrmann's own Preliminary Studies, have shown that the risk of OSA in PCOS is increased at least 5-fold. His recent work shows that roughly half of PCOS women have OSA and suggests that those affected by OSA may be at a much higher risk for development of Type 2 Diabetes Mellitus.

    Ehrmann PubMed publications


  • Murray J. Favus, M.D., Professor

    Department of Medicine

    Head, Metabolic Bone Disease Unit

    mfavus@medicine.bsd.uchicago.edu

    Dr. Favus' work focuses on the pathogenesis of hypercalciuric states and the relation of hypercalciuria to low bone mass and osteoporosis. Basic studies in genetic hypercalciuric rats and clinical studies in patients with genetic idiopathic hypercalciuria are the major areas of investigation. Clinical studies in osteoporosis are also conducted.

    In the area of calcium metabolism, Dr. Favus has identified increases in intestinal, kidney, and bone vitamin D receptor content in genetic hypercalciuric kidney stone forming rats, an animal model of human idiopathic hypercalciuria. This description represents one of the first examples of a disorder (hypercalciuria, stone formation, and low bone mass) caused by a pathologic excess of a steroid hormone. Of particular interest is the role of the estrogen receptor and the vitamin D receptor in the regulation of expression of genes involved in renal calcium transport and the control of hypercalciuria. In clinical studies of osteoporosis, Dr. Favus evaluates the role of hypercalciuria in bone loss and in the use of risk factors to predict fracture risk in postmenopausal women.

    Studies:

    • Ongoing - genetic basis for familial osteoporosis and for familial idiopathic hypercalciuria.
    • Pending IRB approval - mechanism of low bone mass in postmenopausal women with osteoporosis and hypercalciuria.

    Favus PubMed publications


  • Colleen Flynn, M.D., Assistant Professor

    Department of Medicine

    cflynn@medicine.bsd.uchicago.edu

    Dr. Flynn has completed fellowship training in both Endocrinology and Hypertension.  Her clinical practice focuses on the treatment and management of hypertension in the setting of diabetes, and due to abnormalities of the adrenal gland and obesity.  She is conducting research with Dr. Bakris and Dr. Brady in the area of obesity hypertension, investigating the interaction between the adipocyte and aldosterone in postmenopausal women.

     

    Flynn PubMed publications


  • Siri Atma Greeley, M.D., Ph.D., Assistant Professor

    Department of Pediatrics

    sgreeley@peds.bsd.uchicago.edu

    Dr. Greeley's research and clinical focus is on patients with neonatal diabetes (NDM). He has established the national Neonatal Diabetes Registry, which now includes over one hundred probands with diabetes under a year of age. About 50% of those diagnosed under 6 months carry a mutation in either subunit of the KATP channel and can be treated with oral sulfonylureas in lieu of insulin. Dr. Greeley facilitates this transition in patients who subsequently have had a dramatic improvement in metabolic control and quality of life. Dr. Greeley participates in the search for new diabetes genes through probands with NDM and no known genetic cause. As part of a multifaceted investigation, Dr. Greeley recently started a study of certain patient groups in whom beta cell function may be improved by various treatments. Further, he is collaborating with Michael Msall, Chief of Developmental Pediatrics to develop a screening methodology for identification of those with neurodevelopmental and behavioral disabilities and with Eve Van Cauter and Leila Gozal to study the complex interplay between metabolic dysregulation and sleep in our patient population.

    Greeley PubMed publications


  • Manami Hara, D.D.S., Ph.D., Research Associate

    Department of Medicine

    mhara@midway.uchicago.edu

    Dr. Hara's research focus is on the developmental biology of pancreatic islets. The islet of Langerhans is a micro-organ composed of insulin-secreting beta-cells and other endocrine cells that work together to maintain glucose homeostasis. Using novel mouse models combined with sophisticated imaging techniques of the whole mouse pancreas, we have proposed a new model of islet formation including mathematical modeling. Ongoing studies include the islet development in large animals (pigs, monkeys and humans) as well as the pathogenesis of disease states such as type 1, type 2 and early-onset diabetes.

    Hara PubMed publications


  • Dorit Koren, M.D., Assistant Professor

    Department of Pediatrics

    dkoren@medicine.bsd.uchicago.edu

    A pediatric endocrinologist, Dorit Koren, MD, provides care for children and adolescents with hormone disorders, including obesity, sleep disorders, growth hormone deficiencies, and diabetes.

    Dr. Koren studies the link between sleep and obesity-related co-morbidities, including type 2 diabetes and cardiovascular disease. She focuses on applying her findings to patient care, with the goal of reducing the risk of co-morbidities in obese adolescents.

    In addition, Dr. Koren is an active teacher, educating medical students, residents and fellows about endocrine disorders. She also serves as a manuscript reviewer for scientific journals such as Sleep and the Journal of Pediatrics.

    Koren PubMed publications


  • Elizabeth Littlejohn, M.D., Assistant Professor

    Department of Pediatrics

    ebaumann@peds.bsd.uchicago.edu

    Dr. Littlejohn studies various aspects of Type 2 Diabetes Mellitus in children. She is involved in accruing data for the childhood arm of Dr. Robert Rosenfield's study of the genotypic/phenotypic relationship in females with Polycystic Ovary Syndrome (PCOS) by developing the normative data for the frequently sampled oral glucose tolerance test (fsOGTT) to be used to investigate these individuals. Dr. Littlejohn studies children at risk for PCOS, specifically children with Type 1 and Type 2 Diabetes Mellitus with regard to their insulin sensitivity. She compares the various methods used to study insulin resistance such as the hyperinsulinemic-euglycemic clamp versus the frequently sampled intravenous glucose tolerance test and the fsOGTT. She is also interested in specifically dissecting the insulin secretory parameters in children with hyperandrogenism and insulin resistant hyperinsulinism with or without glucose intolerance. She is also characterizing a subgroup of minority children with Type 2 Diabetes in Chicago with Dr. Rebecca Lipton, Ph.D., called Atypical Diabetes Mellitus.

    Littlejohn PubMed publications 

    Dr. Littlejohn's earlier publications will be found under author "Elizabeth Baumann".


  • Silvana Pannain, M.D., Assistant Professor

    Department of Medicine

    spannain@medicine.bsd.uchicago.edu

    Dr Pannain's clinical and research interests include obesity; the metabolic syndrome, and related health conditions such as obstructive sleep apnea and diabetes. Specifically her clinical interest has been to develop Chicago Weight, an interdisciplinary weight loss program and support group at the University of Chicago.

    In her research, Dr Pannain has investigated the metabolic and endocrine aspects of chronic partial sleep loss, and has recently expanded on those research questions by analyzing sleep patterns of obese subjects and their relationship to metabolic, depression, and quality of life measures.

    Studies:

    • Cardio-metabolic Risk of Shift Work: Sleep Loss vs. Circadian Disruption
      Role: Co-Investigator (PI Van Cauter)
      Tests the hypothesis that shift workers who are chronically exposed to circadian misalignment and sleep loss have a higher cardio-metabolic risk than day workers, after controlling for the accumulated sleep debt.
    • Impact of Exenatide on Sleep and Circadian Function in Type 2 Diabetes
      Role: Co-Investigator (PI Van Cauter)
      Tests the hypothesis that treatment with exenatide, a GLP-1 agonist, improves sleep duration and quality in type 2 diabetes.
    • Pilot Study Home sleep and circadian phase: mediators of racial disparities in diabetes risk
      Role: Co-Investigator (PI Van Cauter)
      The goal of the proposed research is to examine whether differences in habitual sleep and at-home circadian phase partially explain diabetes disparities between African-Americans and whites.
    • Sleep quality in obese individuals without significant obstructive sleep apnea
      Role : Co-Investigator (PI Van Cauter)
      Investigation of the effect of obesity per se' on sleep quality.

    Pannain PubMed publications


  • Louis H. Philipson, M.D., Ph.D., Professor

    Departments of Medicine and Pediatrics

    Director, Kovler Diabetes Center

    l-philipson@uchicago.edu

    Louis Philipson, MD, PhD, is Director of Kovler Diabetes Center and Professor of Medicine and Pediatrics. He is a leading world authority on diabetes mellitus, and his research focuses on the biophysical, molecular and genetic aspects of insulin secretion, and monogenic diabetes.

    Dr. Philipson was a co-discoverer of insulin gene mutations causing neonatal diabetes, a novel class of mutations causing diabetes through beta cell ER stress. These mutations are now known to be the second most common cause of permanent neonatal diabetes as well as rare causes of later onset diabetes. Dr. Philipson, together with his colleagues Drs Bell, Greeley and Naylor, is a resource for monogenic diabetes in the United States, following more than 100 patients diagnosed with neonatal diabetes and several hundred with MODY type diabetes. The team has also recently established the first United States registry for neonatal and monogenic diabetes.

    Dr. Philipson is co-director of the Human Islet Transplantation project at the University of Chicago. He has served as principal investigator on numerous research projects and has been widely published in biomedical journals including the Proceedings of the National Academy of Sciences, Science, Nature, Diabetes, American Journal of Physiology and the Journal of Biological Chemistry. Clinically he focuses on type 1 diabetes and complicated type 2 diabetes, monogenic diabetes and hypoglycemia. Currently President of the Chicago/Northern Illinois board of the American Diabetes Association and also a member of its National Board, he has been an invited speaker and presenter at scientific research conferences and symposia worldwide.

    Philipson PubMed publications


  • Samuel Refetoff, M.D.

    Departments of Medicine and Pediatrics

    Committee on Genetics

    refetoff@uchicago.edu

    Dr. Refetoff is Director of the Endocrinology Laboratory and the Principal investigator of a Training Program in Endocrinology and Metabolic Diseases supported by the National Institutes of Health. The contributions made by Dr. Refetoff and his group to our understanding of thyroid hormone action exemplify the strength of combining careful clinical observation and characterization with state-of- the-art in vitro systems utilizing modern approaches of cellular and molecular biology.

    When Dr. Refetoff first described the syndrome of resistance to thyroid hormone (RTH) in 1967, patients with this disorder were characterized from a clinical standpoint but the molecular nature of the defects remained speculative until 1989, when his group identified the first thyroid hormone receptor beta gene mutation causing RTH. Using material obtained from more than 250 families with dominantly inherited RTH, Dr. Refetoff together with Dr. Roy E. Weiss, Chief of the Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, have explored the molecular mechanisms by which different forms of the mutant thyroid hormone receptor alter the function of the normal receptor. They established a world-wide registry for RTH containing clinical and laboratory information on about 500 families with this syndrome. Subsequently, Drs. Weiss and Refetoff identified RTH in humans without thyroid hormone receptor gene mutations and in animals deficient in the nuclear coactivator-1. Their current studies utilize animal models of RTH including thyroid hormone receptor knock outs and animals with adenovirus mediated transfer of mutant receptors.

    Dr. Refetoff also discovered the syndrome of resistance to TSH and demonstrated that it is caused by loss-of-function mutations in the TSH receptor gene. He has identified mutations in the thyroxine binding globulin, transthyretin and albumin genes which result in abnormalities of thyroid hormone transport, as well as defects in the peroxidase gene that cause congenital hypothyroidism. More recently, his laboratory identified two syndromic thyroid defects combining neuropsychological and thyroid abnormalities caused by mutations in the transcription factor, TTF1 (2002) and the thyroid hormone transporter, MCT8 (2004) genes. In 2005 his laboratory identified a defect of TH metabolism caused by mutations in the SBP2 gene, which is involved in the synthesis of selenoproteins.

    The combination of clinical and basic investigations of inherited syndromes of thyroid disorders serves as an ideal training ground for young physician scientists.

    Studies/Projects:

     

    TITLE

    INVESTIGATORS

    IBC (Institutional Biosafety Committee)
    Definition of the state of resistance to thyroid
    hormone (adeno)

    Refetoff S (Prin. Invest.)
    Weiss RE (Co-Invest.)

    Thyroid hormone and RNA synthesis in human fibroblasts

    Refetoff S (Prin. Invest.)
    Weiss RE (Co-Invest.)

    IRB (Human subjects - Institutional Review Board)
    Definition of the states of resistance to thyroid
    hormone (RTH clinical)

    Weiss RE (Prin. Invest.)
    Refetoff S (Co-Invest.)

    Screening for inherited thyroid defects (DNA)

    Refetoff S (Prin. Invest.)
    Weiss RE (Co-Invest.)

    Analysis of human autopsy tissues

    Refetoff S (Prin. Invest.)
    Weiss RE (Co-Invest.)

    Studies on Syndromes of Resistance to TSH

    Weiss RE (Prin. Invest.)
    Refetoff S (Co-Invest.)

    Fine Needle Aspiration of the Thyroid in Subjects with Inherited Thyroid Disease

    Weiss RE (Prin. Invest.)
    Refetoff S (Co-Invest.)

    IACUC (Animal subjects - Institutional Animal Care and Use Committee)
    Studies on regulation and mechanisms of hormone action (isotope/mouse)

    Weiss RE (Prin. Invest.)
    Refetoff S (Co-Invest.)

    Studies on regulation and mechanisms of hormone action (non-breeding)

    Refetoff S (Prin. Invest.)
    Weiss RE (Co-Invest.)

    RADIOISOTOPE
    University of Chicago Radioactive Materoa

    Refetoff S (Prin. Invest.)

    Refetoff PubMed publications


  • Christopher J. Rhodes, Ph.D., Kovler Family Professor

    Chairman, Committee on Molecular Metabolism and Nutrition (CMMN)

    Associate Director for Research, Kovler Diabetes Center

    Department of Medicine

    cjrhodes@uchicago.edu

    Dr. Rhodes’ research focuses on signal transduction mechanisms in the pancreatic ß-cells that control their function, especially insulin production and secretion. It is now widely acknowledged that the onset of type-2 diabetes is marked by ß-cell secretory dysfunction and death. Dr. Rhodes’ laboratory also investigates molecular signal transduction mechanisms that control ß-cell growth and survival, with a view to finding novel therapies that delay the onset and perhaps even prevent diabetes.

    Currently, his laboratory has several ongoing research projects including unveiling the molecular mechanism behind specific translational control of proinsulin biosynthesis (the major regulation of insulin production); examining the role of FoxO and NFAT transcription factors in controlling IRS-2 gene expression in ß-cells that is key for their survival; investigating H2O2 as a bona fide nutrient generated secondary signal in ß-cells; unraveling the CNS neuronal network that controls pancreatic endocrine ß- and α-cell function; examining the interface between the ß-cell and immune system in the pathogenesis of type 1 diabetes; and also, functionally evaluating ‘insulin-producing cells’ derived from alternative sources, such as human embryonic stem cells, that might eventually be used as surrogate ß-cells as a cell-replacement therapy to treat type 1 diabetes.

    Rhodes PubMed publications


  • Robert M. Sargis, M.D., Ph.D., Instructor

    Department of Medicine

    rsargis@medicine.bsd.uchicago.edu

    A native of Chicago, Dr. Sargis received his undergraduate education at Carleton College in Northfield, Minnesota then returned to complete an MD/PhD at Rush University before coming to the University of Chicago for his internship, residency, and endocrinology fellowship as part of the Physician-Scientist Development Program in the Department of Medicine. As a fellow, Dr. Sargis conducted his research training in the laboratory of Matthew Brady, PhD studying the effects of environmental endocrine disruptors on adipocyte differentiation. Joining the faculty in 2010, his clinical work focuses on diabetes and lipid disorders, and his research continues to explore the effects of endocrine disruptors on metabolism.

    Sargis PubMed publications


  • Donald Steiner, M.D., A.N. Pritzker Distinguished Service Professor

    Service Professor Emeritus (Active)

    Department of Medicine

    dfsteine@uchicago.edu

    The seminal discovery by Dr. Steiner that insulin is formed via a single chain precursor proinsulin, that undergoes post-translational modification, serves as a model of peptide hormonal synthesis and is the basis of ongoing research in this area. More recently, the primary focus of his laboratory has been the major neuroendocrine prohormone convertases PC2 (SPC2) and PC1/PC3 (SPC3), their biosynthesis, maturation and actions on prohormone processing. For these studies he is using mice with targeted disruptions in their genes and mutational analysis of the structure and functional significance of conserved subdomains in these convertases. Additional studies involve the mechanisms of processing of insulin-like growth factor precursors and the effect of the furin gene on proinsulin processing and islet morphogenesis.

    Other interests are insulin receptor structure biosynthesis, maturation through chaperone interaction, and intracellular transport. He is probing the evolution of insulin and the IGFs and their receptor proteins in lower vertebrates, with emphasis on the divergence of ligand binding, metabolic and growth regulatory functions from a single ancestral insulin-like peptide and its receptor in protochordates.

    Studies:

    • Investigate how insulin binds to and activates its receptor
    • Islet and prohormone convartase studies

    Steiner PubMed publications


  • Eve Van Cauter, Ph.D., Professor

    Department of Medicine

    Director, Chronobiology and Sleep Disorder Laboratory

    evcauter@medicine.bsd.uchicago.edu

    Dr. Van Cauter is an internationally known investigator in circadian rhythms on endocrine systems in normal and pathological conditions. She is also an expert in the mathematical and statistical analysis of the temporal patterns of hormonal secretion and the effects of sleep on endocrine function.

    Dr. Van Cauter is the Principal Investigator of a Program Project which is focused on the age-related changes in circadian rhythms. Particularly interesting from a physiologic and therapeutic standpoint are studies which aim to investigate whether replacement of growth hormone in early sleep or restoration of elevated nocturnal melatonin levels, two hormonal events which are thought to act as internal synchronizers in young adults, may correct circadian rhythm alterations in older subjects. Dr. Van Cauter has also determined the utility of the use of hormonal rhythms as markers of the human circadian clock in basic studies examining the mechanisms of entrainment of hormonal rhythms, and their implication for adaptation to jet lag and shift work. In addition, Dr. Van Cauter is one of five preceptors in the Northwestern University-University of Chicago NIH training grant for Sleep Research.

    In recent years, she has led a major research program evaluating the impact of sleep loss on endocrine and metabolic function and the possible endocrine benefits of improved sleep quality in older adults.

    Van Cauter PubMed publications


  • Tamara Vokes, M.D., Associate Professor

    Department of Medicine

    Director, Physician Directed Practice

    Director, Adult Endocrine Fellowship Program

    tvokes@medicine.bsd.uchicago.edu

    Dr. Vokes has a clinical program that focuses on osteoporosis and other metabolic bone diseases. Patients are referred from within the institution as well from the Chicago metropolitan area and the Midwest. As a result, the fellows rotating through this clinic are exposed to wide range of bone pathology.

    Dr. Vokes' research interest is also in the area of osteoporosis and metabolic bone disease. In the area of osteoporosis, Dr. Vokes has investigated novel approaches to refining the assessment of fracture risk. Among those, she has pioneered the clinical application of Vertebral Fracture Assessment (VFA) in improving identification of patients with highest fractures risk who may need the most aggressive therapeutic approach. In addition, she has studied the possibility of detecting bone fragility using a new method for non-invasive assessment of bone structure known as Radiographic Texture Analysis (RTA) of bone images. This work is done in collaboration with a medical physicist, Dr. Maryellen Giger and has shown promising results demonstrating the utility of RTA in assessing bone fragility. Finally, Dr. Vokes is examining racial differences in fracture risk particularly in relationship to the effects of glucocorticoids on bone fragility, which may differ between Caucasian and African American subjects.

    In the area of metabolic bone disease, Dr. Vokes is participating in the multicenter clinical trial using PTH replacement therapy for patients with hypoparathyroidsim, the last hormone deficiency syndrome for which hormone replacement therapy has not been available to date. The results of this trial are very promising and are likely to revolutionize the treatment of this disease.

    Protocols:

    • Clinical, Radiographic, Histologic and Molecular Characterization of Bone Fragility
    • Search for Genetic and Molecular Defects Causing Unexplained Bone Fragility
    • Clinical utility of computerized analysis of bone structure (texture analysis) in diagnosing osteoporosis - comparison to currently approved methods for assessing bone density
    • Changes in bone density, texture analysis of bone radiographs and bone turnover during two years of antiresorptive therapy in postmenopausal osteoporosis
    • Population study to establish normative data for Radiographic Texture Analysis (RTA) and bone mineral density (BMD) of the calcaneus in African American and Caucasians
    • A Randomized, Dose-blinded Study to Investigate the Safety and Efficacy of NPSP558, a Recombinant Human Parathyroid Hormone [rhPTH(1-84)], at Fixed Doses of 25 micrograms and 50 micrograms for the Treatment of Adults With Hypoparathyroidism
    • A 12-Month Open-label Study Investigating the Safety and Tolerability of NPSP558, a Recombinant Human Parathyroid Hormone (rhPTH [1-84]), for the Treatment of Adults with Hypoparathyroidism A Clinical Extension Study (RACE)
    • Comparison of bone mineral density (BMD) and vertebral fracture status between treated and untreated head, neck and esophageal cancer (HNE CA) patients
    • Racial differences in vulnerability to corticosteroid induced osteoporosis in patients with cardiac organ transplants

    Vokes PubMed publications


  • Barton Wicksteed, Ph.D., Assistant Professor

    Department of Medicine

    bwickste@medicine.bsd.uchicago.edu

    Cyclic AMP (cAMP) is a second messenger molecule that provides considerable potential in the treatment of Type 2 Diabetes. Raising cAMP in the islet beta-cells can enhance glucose stimulated insulin secretion, leading to better glucose control. cAMP can also protect beta-cell mass by preventing beta-cell death and enhancing beta-cell proliferation. The therapeutic potential of cAMP in the beta-cells was the basis for the development of drugs such as exendin-4 (Byetta) and DPP-4 inhibitors (Sitagliptin). However, the mechanisms by which cAMP signals in the beta-cell are largely unknown, which limits our ability to take full advantage of this signal pathway.

    To improve our understanding of cAMP signal in the islet beta-cell, Dr. Wicksteed’s lab is studying one of the major downstream targets of cAMP, the cAMP-dependent protein kinase, PKA. To understand the role of PKA in the regulation of insulin secretion and the potential that this has for control circulating glucose levels, they are developing mouse models to understand the physiological consequences of altering beta-cell PKA activity in vivo. These studies use two mouse models, one that activates PKA signal in the beta-cells and one that inhibits beta-cell PKA activity. These mice are used to study the short effects upon insulin secretion and beta-cell mass. In addition, Dr. Wicksteed’s lab is conducting longer term experiments to determine whether altering beta-cell PKA activity can affect insulin sensitivity in insulin target tissues, and can affect the expansion and preservation of beta-cell in the progression from normal glycemia to insulin resistance to Type 2 Diabetes. Complementing these experiments, in vitro experiments to understand the targets and signaling complexes of PKA signaling in islet beta-cells are also being performed. The aim of these experiments is to develop a better understanding of the mechanism of cAMP signaling and to identify other potential targets of cAMP that can be the focus for developing new therapeutic approaches to treat Type 2 Diabetes Mellitus. Dr. Wicksteed is also interested in using their mouse models to study whether raised cAMP levels can show potential for treating Type 1 Diabetes or some of the persistent neonatal forms of diabetes.

    Wicksteed PubMed publications


  • Christine Yu, M.D., Assistant Professor

    Department of Pediatrics

    cyu@peds.bsd.uchicago.edu

    Dr. Yu is board-certified in both adult and pediatric endocrinology and specializes in transitional care for adolescents and young adults with chronic endocrinologic disease, including hypopituitarism, Turner syndrome, and endocrinologic complications of cancer survivors. She is currently investigating puberty initiation in Turner syndrome.

    Clinical Research:

    • Gonadotropin Releasing Hormone (GnRH) Agonist Test in Disorders of Puberty

    Publications:

    • Gregg B, Kociolek LK, Qin K, Rosenfield RL, Yu C. P450c17 deficiency caused by compound heterozygosity for two novel mutations presenting as hypotension in early infancy. Horm Res Pediatr. 2011. 76:434-441
    • Yu C, Markan K, Temple KA, Deplewski D, Brady MJ, Cohen RN.  The nuclear receptor corepressors NCoR and SMRT decrease PPARg transcriptional activity and repress adipogenesis.  J Biol Chem.  2005.  280:13600-5
    • Temple KA, Cohen RN, Wondisford SR, Yu C, Deplewski D, Wondisford FE.  An intact DNA-binding domain is not required for PPARg binding and activation on some PPAR response elements.  J Biol Chem.  2005.  280:3529-40
    • Cohen RN, Cohen LE, Botero D, Yu C, Sagar A, Jurkiewicz M, Radovick S.  Enhanced repression by HESX1 as a cause of hypopituitarism and septo-optic dysplasia.  JCEM.  2003.  88:4832-9
    • Book Review: Yu C.:  Allgrove J et al, eds.  Evidence-based Paediatric and Adolescent Diabetes.  Pediatrics. 2008. 122:458

  • Outcomes Research Faculty in the Endocrine Training Program

  • Arshiya Baig, M.D., Assistant Professor

    Department of Medicine

    agaig@medicine.bsd.uchicago.edu

    Dr. Baig's main research interests are in mitigating health disparities in Latino populations. Her work to date has focused on: 1) using community-based participatory research methods to improve healthcare delivery to low-income minority communities; and 2) designing and evaluating church-based diabetes interventions to improve outcomes among Latinos; 3) formulating ways to use health information technology to address diabetes disparities; and 4) assessing services for Latino patients at community health centers.

    Baig PubMed publications


  • Deborah Burnet, M.D., M.A., Professor

    Departments of Medicine, and Pediatrics

    Chief, Section of General Internal Medicine

    Department of Medicine Vice Chair, Faculty Development

    dburnet@medicine.bsd.uchicago.edu

    Dr. Burnet conducts research on obesity and prevention of type 2 diabetes in youth. Dr. Burnet designed and implemented a community-based, family oriented program. This program, called the REACH-OUT Children's Diabetes Prevention Program, is designed to decrease obesity and risk of type 2 diabetes among African-American youth. Her other areas of interest include faculty development, cultural competence and inequalities and health. Clinical interests are primary care for adults and children, obesity, and Type 2 Diabetes in youth.

    Research Projects:

    • COACH - Combating Obesity at Community Health Centers. A collaborative among 5 Midwestern community health centers to conduct quality improvement initiatives on their weight management programs. Health center staff participated in three two-day workshops at UC to learn quality improvement techniques, then implemented QI programs at their centers to improve participant recruitment and retention and other aspects of weight management programs. Monthly conference calls enabled sharing of experience across centers. Outcomes varied by center, but health center staff appreciated learning QI approaches and reported improvements in their ability to recruit and retain participants. Publication of more detailed process measures and outcomes is pending.
    • Power-Up - Collaborative After-School and Cell-phone Texting Intervention to Prevent Obesity. We piloted the Power-Up healthy nutrition and physical activity program in the after-school setting at Woodlawn Community School. 40 children in grades K-6 participated as subjects. At baseline, half the children were obese or overweight. Mean BMI z-score declined significantly over the course of the 14 week intervention. A cell-phone texting component was added to engage parents in healthy behavior change, as parents were generally not available during after school. Parents were quite engaged; cell-phone texting appears to be a feasible and effective way to engage parents in this intervention. Planning for a randomized trial of the Power-Up intervention in 10 schools is underway.

    Burnet PubMed publications


  • Marshall H. Chin, M.D., M.P.H., Professor

    Department of Medicine

    Director, Chicago Center for Diabetes Translation Research

    mchin@medicine.bsd.uchicago.edu

    Dr. Chin is a general internist and health services researcher with extensive experience improving the care of vulnerable patients with chronic disease.  With Monica Peek, M.D., M.P.H., Dr. Chin is co-leading a project to improve diabetes care and outcomes on the South Side of Chicago through health care system and community interventions (www.southsidediabetes.com). He is also leading the evaluation of a Commonwealth Fund project that is implementing the patient-centered medical home in 65 safety net clinics across five states.  Dr. Chin directs the Robert Wood Johnson Foundation Finding Answers: Disparities Research for Change Program that seeks to identify and disseminate interventions to reduce racial and ethnic disparities in health care

    Chin PubMed publications


  • Monica Peek, M.D., M.P.H., Assistant Professor

    Department of Medicine

    mpeek@medicine.bsd.uchicago.edu

    Dr. Peek's broad research interests include health disparities, particularly as related to chronic disease management and preventive health care. She has focused her research on diabetes and breast cancer screening. She is currently exploring how race and culture impact the patient/provider relationship, shared decision-making and diabetes health outcomes. Dr. Peek's clinical interests include preventive health care, chronic disease management, patient education, and women's health.

    Peek PubMed publications


  • Faculty Outside of Endocrinology that Participate in the Endocrine Training Program

    Eugene B. Chang, M.D. (Martin Boyer Professor)
    Dr. Chang is studying the intestinal absorption of nutrients, electrolytes, and water. He is particularly interested in a specific family of sodium-transporting proteins known as Na-H exchangers, which play a major role in non-nutrient dependent salt absorption by the kidney and intestine. Many diarrheal diseases appear to be caused by the inhibition or impairment of these proteins. Dr. Chang has examined the effects of chronic diabetes and extensive small bowel resection on intestinal function, as they provide insights into mechanisms of intestinal adaptation. A number of studies related to glucose transporters of the intestinal epithelium were performed in collaboration with Charles Burant, a former member of the training faculty. The expression of these transporters are significantly altered in diabetes and after extensive small bowel resection, partly related to hormonal signals and, in other instances, to dietary and luminal factors. Current research is attempting to define the signals that are involved in altering transcription and post-transcriptional processes of the Na-H exchangers.

     

    Nancy Cox, Ph.D. (Professor)
    Nancy J. Cox, Ph.D. is Professor of Medicine and Human Genetics, and Chief of the Section of Genetic Medicine. Her research is in quantitative human genetics, and is currently focused on developing methods for identifying and characterizing the genetic component for complex disorders through genome-wide association studies. Among the disorders currently under investigation in the Cox Lab using genome-wide association are Type 1 and Type 2 Diabetes and diabetic complications, asthma and associated quantitative traits, stuttering, specific language impairment, Tourette Syndrome, and mesothelioma.

     

    Godfrey Getz, M.D., Ph.D. (Louis Block Professor)
    Dr. Getz’s group is studying the role of the immune system and apolipoprotein A-I in atherosclerosis in mouse models of the disease. The basic models are the apo E and the LDL Receptor deficient mice. In these contexts three aspects of the immune system are studied--global immune deficiency via RAG (recombination activation gene) deficiency modifications of one of the T cell subsets, NKT cells both by overexpression and deficiency, and the system of costimulatory molecules (second signal) belonging to the TNF superfamily, LIGHT and lymphotoxin, also either by overexpression and deficiency. Each of these interventions affects both lipid homeostasis and vessel wall lesions by mechanisms that are now under detailed investigation. The role of the immune system impacting lipid metabolism is relatively novel and exciting. These studies have an impact on the understanding of atherogenesis and on the fact that atherosclerotic heart disease is much more common in auto-immune diseases.

     

    Theodore Karrison, Ph. D. (Assistant Professor)
    Dr. Karrison is an experienced statistician whose statistical research interests include clinical trials methodology, survival analysis, and methods for analyzing multiple endpoints. Dr. Karrison presents a didactic lecture series on statistical methods on an annual basis which all trainees are encouraged to attend. In his function as statistical consultant to the Clinical Resource Center, he provides a detailed critique of the proposed studies design and statistical methods. Trainees are encouraged to interact individually with Dr. Karrison to receive advice on the best approach to the statistical analysis of their own data.

     

    Anthony Kossiakoff, Ph.D. (Otho S.A. Sprague Professor and Chairman, Department of Biochemistry)
    Dr. Kossiakoff’s research interests are in the areas of protein engineering and design using X-ray crystallography, mutagenesis, and peptide synthesis.

    The studies in Dr. Kossiakoff’s laboratory are focused on the broad objective of understanding ligand-receptor interactions. The structures of several hormone-receptor complexes will be solved to provide the structural basis for resolving the role of conformational versatility in determining the binding and specificity of these molecules. The work will also include a set of integrated phage display mutagenesis studies to dissect the cooperativity effects and energy contributions of the residues forming the binding interfaces.

     

    Ronald A. Thisted, Ph. D. (Professor and Chairman, Department of Health Studies)
    Dr. Thisted, a biostatistician/epidemiologist, is studying regression methods for paired data with ordered categorical outcomes, problems of multiple inference in clinical trials, methods for combining information (meta-analysis) concerning diagnostic tests such as those used in nuclear medicine, and assessment of causal relationships associated with rare but catastrophic events such as sudden death in children. He will be responsible for aspects of the training related to biostatistics and data analysis.