Graeme I. Bell, Ph.D. Dr. Bell is a leading authority on the molecular genetics of diabetes mellitus and directs a large and active program which aims to identify diabetes susceptibility genes. He has identified certain genes that are responsible for the autosomal dominantly transmitted maturity-onset diabetes of the young (MODY). These include the genes for the glycolytic enzyme glucokinase and the transcription factors, hepatocyte nuclear factor 1alpha, -1ß and -4alpha and insulin promoter factor-1. Clinical studies indicate that mutations in each of these genes affects the normal function of the insulin-producing cells of the pancreas.

Genetic studies of families with type 1 and type 2 diabetes, two forms of diabetes that result from the interactions of multiple susceptibility loci and lifestyle factors, have allowed Bell to determine the chromosomal localization of genes that contribute to the development of each of these disorders. Efforts are underway to identify the susceptibility loci for type 1 and type 2 diabetes and determine how they contribute to the development of these forms of diabetes.

Close interactions with colleagues who are interested in the phenotypic characterization of patients with genetic forms of diabetes has created learning opportunities for trainees interested in bench research as well as those more clinically and physiologically oriented.

Matthew Brady, Ph.D. Dr. Brady is studying the hormonal regulation of glycogen metabolism. He has identified a novel PP1 regulatory subunit, termed PTG for Protein Targeting to Glycogen. This molecule binds to PP1 and glycogen and to several PP1 substrates that are key enzymatic regulators of glycogen metabolism. Results indicate that PTG acts as a molecular scaffold, assembling PP1 with specific substrate proteins, allowing for the efficient hormonal regulation of glycogen metabolism. To determine the effect glycogen has on insulin secretion from pancreatic ß-cells and insulin metabolic signaling, he plans to generate transgenic mouse lines with beta cell specific expression of PTG constructs, and to examine islet differentiation and function in vivo.

A second major project in his lab is the interdependency of intracellular glycogen levels and insulin metabolic signaling in 3T3-L1 adipocytes. By over-expression of PTG in these cells, he plans to determine whether adipocytes be made to shunt more stored energy from lipid to glycogen, the ramifications of altering adipose tissue glycogen stores on whole animal metabolism, diet induced obesity and insulin resistance.

Ronald Cohen, M.D. Dr. Cohen is investigating the role of corepressors in thyroid hormone action. The thyroid hormone receptor (TR) and retinoic acid receptor (RAR) isoforms have the capacity to silence gene expression in the absence of their ligands on target response elements. This active repression is mediated by the ability of the corepressors, NCoR and SMRT, to recruit a complex containing histone deacetylase activity. Mutations in the TR found in the syndromes of resistance to thyroid hormone can change the corepressor recruited by changing the complex (homodimer or heterodimer) formed on the thyroid hormone response elements. Ongoing studies are examining (1) further mechanisms of the specificity of corepressor recruitment by TR and RAR; (2) the characterization of corepressor function in vitro and in vivo; and (3) the role of transcription factors in thyrotroph and gonadotroph development in the pituitary.

Nancy Cox, Ph.D. Dr. Cox is a human geneticist studying common disorders with complex patterns of transmission. She collaborates with other investigators in studies on type 1 and type 2 diabetes, polycystic ovary syndrome, inherited thyroid defects, asthma, autism, attention deficit/hyperactivity disorder, bipolar disorder and schizophrenia. Her role on these projects includes participation in study design and data management, as well as primary responsibility for genetic analyses, including segregation analysis, linkage analysis, linkage disequilibrium analysis, and genetic analyses conducted in the context of positional cloning studies.

Populations studied include out bred U.S. Caucasian populations, as well as Japanese and Chinese Asian populations. A mixed population including African-American and Mexican-American populations and an inbred isolated population of Hutterites. Because of challenges that have arisen during the course of analyses on these data, Dr. Cox has developed a research program in the development and extension of methods for genetic analysis, particularly linkage analysis.

Dianne Deplewski, M.D. 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 has examined 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 examined the expression of 5alpha-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.

Her future plans are to further her 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 conditioned media.

David A. Ehrmann, M.D. Dr. Ehrmann has developed a clinical research program to study the genetic and physiological basis of defects in insulin secretion in women with polycystic ovary syndrome (PCOS). This is funded by a K08 award from the NIH. Dr. Ehrmann first demonstrated that women with PCOS have a characteristic supranormal elevation of 17-hydroxyprogesterone secretion in response to the endogenous gonadotropin secretion induced by administration of the gonadotropin releasing hormone agonist, nafarelin. He then showed that compaired to weight-matched controls, women with PCOS had ß-cell dysfunction which resembled that of Type 2 diabetes rather than that of simple obesity. Furthermore, his studies showed that women with PCOS who had a first-degree relative with diabetes were significantly more likely to demonstrate alterations in ß-cell function when compared to a matched group of PCOS subjects without a such family history.

The modulation by insulin of 17-hydroxylase and 17,20-lyase activities of the ovarian steroid-forming P450c17 suggests a causal link between hyperinsulinemia and the characteristic features of PCOS. Treatment with troglitazone improved not only the sensitivity to insulin but also reduced significantly the levels of total and free testosterone and the leuprolide-stimulated levels of 17-hydroxyprogesterone, androstenedione and total testosterone.

To examine the genetic basis for defects in insulin secretion and insulin action in PCOS, Dr. Ehrmann has obtained phenotypic data and DNA samples from over 240 families, totaling more than 650 individuals. This database will serve as the key resource for future studies which will focus primarily upon examining defects in pancreatic ß-cell function and genotyping candidate genes implicated in Type 2 diabetes.

Murray Favus, M.D. Dr. Favus’ work centers on the metabolic basis of genetic idiopathic hypercalciuria in calcium oxalate stone formation, in the action of parathyroid hormone and in osteoporosis.

In the area of calcium metabolism, he has identified increases in intestinal 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 and stone formation) caused by a pathologic excess of a steroid hormone. In other studies, Dr. Favus has defined the protein kinase C signaling pathway in rat renal proximal tubules as mediating parathyroid hormone stimulation of the 25-hydroxyvitamin D-1-hydroxylase, a key regulatory enzyme in the vitamin D activation pathway. By this work he was able to assign a pathway to one of parathyroid hormone’s many biologic actions. In clinical studies, Dr. Favus participated in the multi-center trial that found the bisphosphonate alendronate sodium to be effective in the treatment of postmenopausal osteoporosis and he continues to conduct clinical studies that aim to characterize novel approaches to the treatment of osteoporosis and disorders of calcium metabolism.

Manami Hara, D.D.S., Ph.D. Dr. has generated a series of lines of transgenic mice expressing green fluorescent protein (GFP) and DsRed1 under the control of a series of transcription factors that characterize different cell types in the beta cell lineage. She is characterizing the pattern of gene expression in these genetically-tagged cells using expression profiling with Affymetrix GeneChips and custom arrays in order to identify the stem cell which gives rise to the pancreatic beta cell.

Plamen D. Penev, M.D., Ph.D. Dr. Penev’s main focus of research is to examine the metabolic and endocrine aspects of chronic sleep loss as a putative risk factor for obesity, insulin resistance and accelerated metabolic aging. He is using an interdisciplinary integrative approach that includes the simultaneous assessment of metabolic, endocrine, polysomnographic, cardiovascular and neurobehavioral variables. Information derived from these studies should help understand the effects of varying sleep duration on hunger, satiety, food intake, daily energy balance, body fat content, glucose homeostasis and important aspects of the syndrome of insulin resistance in humans.

Louis H. Philipson, M.D., Ph.D. Dr. Philipson has focused his studies on how specific ion channels regulate intracellular calcium concentration and thereby insulin secretion in pancreatic ß-cells in normal and diabetic states. After identifying full length voltage-dependent K+ channels from a human insulinoma, he has studied this family of channels using molecular and biophysical techniques.

More recently, Dr. Philipson has produced a transgenic K+ channel mouse with ß-cell specific K+ channel expression inhibited by dominant-negative approaches. One of these expresses a green fluorescent protein- K+ channel fusion protein under the direction of the rat insulin promoter. From these studies and those utilizing stable transfected insulinoma cells expressing dominant-negative K+ channels it can be concluded that these channels exert a profound effect on intracellular calcium and are an interesting target for approaches to modulate hormone secretion.

Dr. Philipson's laboratory has cloned a channel (trp4) from ßTC3 insulinoma cells that is activated by depletion of Ca2+ from intracellular stores and 1,4,5-inositol trisphosphate. This channel is expressed in mouse and human ß-cells as well as in brain and other endocrine tissues. The mechanisms of beta cell dysfunction in homozygous or heterozygous glucokinase, HNF-1alpha, HNF-4alpha and PDX-1 mutant mice are being studied.

Samuel Refetoff, M.D. Dr. Refetoff is the Director of the Training Program in Endocrinology and Metabolic Diseases. 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 ß gene mutation causing RTH. Using material obtained from more than 100 families with dominantly inherited RTH, Dr. Refetoff has explored the molecular mechanisms by which different forms of the mutant thyroid hormone receptor alter the function of the normal receptor. Dr. Refetoff has established a world-wide registry for RTH containing clinical and laboratory information on about 300 families with this syndrome. More recently he identified RTH in humans without thyroid hormone receptor gene mutations and in animals deficient in the nuclear coactivator-1. His 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, he found that mutation sin the thyroid transcription factor 1 gene produce neurological, respiratory as well as thyroid abnormalities.

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

Sirimon Reutrakul, M.D. Dr. Reutrakul is involved in a multicenter trial to study the effect of aggressive medical anti-ischemia treatment alone or in combination with Bypass Angioplasty Revascularizaiton in type 2 diabetes. Two glycemic control strategies, insulin sensitization versus insulin provision, will be also compared.

In addition in a Diabetes Prevention multi-center trial, persons with impaired glucose intolerance will be subjected to intensive program of diet, exercise and stress reduction versus standard dietary and exercise advice as well as 2) therapy with either metformin or placebo.

Michael Wm. Roe, Ph.D. Dr. Roe is studying the regulation of insulin secretion by defining the subcellular calcium (Ca2+) signaling mechanisms from the perspectives of biophysics, physiology, biochemistry and molecular biology. Using genetically encoded Ca2+ biosensors targeted to the lumen of the endoplasmic reticulum (ER), Dr. Roe is studying ER Ca2+ signaling in normal and diabetic mouse islets. Previously, he found a decrease in sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) activity, an enzyme necessary for regulating ER Ca2+ signaling, in diabetic mouse ß-cells which caused the loss of normal intracellular Ca2+ responses to glucose stimulation and may be related to abnormal insulin secretion. Dr. Roe will restore SERCA expression in diabetic islet cells by molecular engineering approaches to investigate the importance of this Ca2+ signaling defect in ß-cell dysfunction.

Robert Rosenfield, M.D. An expert in disorders of puberty and hyperandrogenic states, Dr Rosenfield has maintained a clinically oriented research program supported by laboratory investigation. He has described the use of the GnRH agonist, nafarelin, to distinguish between ovarian and adrenal sources of androgen, to diagnose ovarian enzymatic defects in women with hyperandrogenism and to differentiate between gonadotropin deficiency and constitutional delay of puberty during the teenage years. The intermittent administration of the GnRH agonist, leuprolide acetate, is being tested in the treatment of adult men and women with gonadotropin deficiency. The transdermal administration of low dose estradiol is being used to potentiate the effect of growth hormone treatment in patients with Turner syndrome.

Dr. Rosenfield developed a system of culturing sebocytes in monolayers by activating the peroxisome proliferator activated receptors (PPARs) in rat preputial cells placed in a chemically defined, serum free medium. Definition of the factors that regulate sebocyte growth and differentiation have important implications for the development of new therapies for acne vulgaris. His long interest in the polycystic ovary syndrome (PCOS) has lead his laboratory to search for the expression of enzymes in the 17-hydroxylase and delta 4-17,20-lyase pathways that have the potential of generating androgens in the human ovary. Dr Qin, a trainee in Rosenfield's laboratory under this program, has recently shown that 17 ß-hydroxysteroid dehydrogenase 5 is expressed in human ovary. The potential role of this enzyme in the hyperandrogenic state of PCOS is being actively explored.

Donald Steiner, M.D. 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 hormone 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.

Xiao Jian Sun, PhD. Dr. Sun is working on the identification and characterization of molecules that involve insulin signal transduction with the ultimate goal of understanding the molecular basis of insulin resistance.

IRS-proteins play an important role in insulin action and insulin resistance. The working hypothesis is that the phosphorylation state of IRS-proteins, controlled by serine/threonine kinases and phosphatases, may predetermine whether cells are sensitive (hypo-phosphorylated) or resistant (hyper-phosphorylated) to insulin. The project involve the identification of the serine/threonine phosphorylation sites in IRS-1, and potential serine/threonine kinases or phosphatases. Dr. Sun has found that IRS-protein levels are controlled by a ubiquitin-dependent proteasome degradation pathway. He is currently studying elements and proteins that participate in the regulation of IRS-protein degradation in normal and insulin resistant state.

Eve Van Cauter, Ph.D. Dr. Van Cauter is an internationally known investigator in circadian rhythms on endocrine system 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.

Tamara Vokes, M.D. Dr. Vokes is the Director of the Endocrinology Clinic. She spends 6 half days a week in the clinic where she sees patients with a wide range of endocrine diseases. Her special interests are in osteoporosis which constitutes a large portion of her practice. In addition, she has a large cohort of diabetic patients who use an insulin pump and she has experience with various insulin regimen and different types of monitoring devices including glucose sensor.

Dr. Vokes’ research interest is in the area of osteoporosis. Currently, she is involved in a multi-center trial of new treatment with parathyroid hormone. She is collaborating with medical physicists on a project which deals with use of computerized analysis of bone radiographs as a means of evaluating bone structure. She is also collaborating with pediatric gastroenterologists on developing a trial of biphosphonates in treatment of children receiving glucocorticoids for inflammatory bowel disease. Another area of her activity has been screening geriatric patients for osteoporosis with the goal of defining the prevalence of this condition and its correlation with frailty.

Gene C. Webb, Ph.D. Dr. Webb is studying the function of the pancreatic beta cell through the use of microarray technology. By whole-genome expression profiling of stimulated murine beta cells, a he plans to identify those genes most important for beta-cell function. Work has demonstrated that genes functioning in the secretory pathway, metabolic pathways, transcription factors and signal transduction are key components in beta-cell function. A second line of research is the identification of genes expressed in human islet preparations that are important for successful islet transplantation using the newly developed Edmonton protocol. This work has yielded a defined set of human genes that either positively or negatively affect the ability of transplanted islets to cure diabetes following transplantation.

Roy Weiss, M.D., Ph.D. Dr. Weiss is Associate Director of the Clinical Research Center and Director of the Core laboratory. His research centers on the mechanisms of thyroid hormone action at the molecular, physiological and psychological levels. Dr. Weiss has examined the relationship between childhood Attention Deficit Disorder (ADD) and resistance to thyroid hormone (RTH). While previous studies have suggested a high incidence of ADD in patients with resistance to thyroid hormone (RTH) his prospective study of 277 children with ADD showed no instance of RTH although a 5.4% incidence of thyroid disorders was seen (normal in this age population < 1%). Hyperactivity appears to be improved in some patients with RTH and ADD who are treated with thyroid hormone but not in patients with ADD alone.

In other studies, Drs. Weiss and Refetoff have identified new mutations in the ß isoform of the thyroid hormone receptor and variable clinical and biochemical manifestations of RTH in different families harboring the same receptor mutation, suggesting that co-modulatory factors determine the phenotype in this syndrome. In separate studies, Dr. Weiss studied a large Amish kindred with familial dysalbuminemic hyperthyroxinemia (FDH) and identified a mutation in the albumin gene with increased affinity for thyroxine. More recently, Dr. Weiss has been involved in the study of mice deficient in the thyroid hormone receptor isoforms and related cofactors. He has developed a clinical research program to study pituitary tumors and in particular Cushing's syndrome.

Andrew Wolfe, Ph.D. Dr. Wolfe is studying the molecular elements that regulate gonadotropin-releasing hormone (GnRH) gene expression and in turn reproductive function by controlling the pituitary secretion of LH and FSH. In mammals, the reproductive process requires a tremendously large energy expenditure. The reproductive system is, therefore, acutely sensitive to a variety of cues regarding the availability of nutrition and the levels of stored energy. The mechanisms by which nutritional information is transmitted to the brain, and ultimately to the GnRH neurons are not well understood. It has been suggested that insulin may regulate reproduction via signaling pathways in the brain. One project in his laboratory is to explore a role for insulin in the regulation of reproduction, focusing on a potential direct effect of insulin on GnRH neurons

FACULTY OUTSIDE ENDOCRINOLOGY THAT PARTICIPATE IN THE TRAINING PROGRAM

Eugene B. Chang, M.D. Dr. Chang is studying the absorption of nutrients, electrolytes, and water from the intestinal tract. 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. 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 fo 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.

Marshall H. Chin, M.D., M.P.H. Dr. Chin is the Director of the DRTC Prevention and Control Core, Associate Director of the Robert Wood Johnson Clinical Scholars Program. He and his colleagues from a consortium of 70 community health centers in the Midwest are currently funded by the Agency for Healthcare Research and Quality (AHRQ) and Robert Wood Johnson Foundation to improve the quality of diabetes care in health centers that serve the indigent. This multifactorial, community-based intervention includes rapid quality improvement, chronic disease management, provider training in behavioral change, and patient empowerment interventions. Dr. Chin also focuses on geriatric diabetes issues to assess the treatment preferences of older patients with diabetes.

Godfrey Getz, M.D., Ph.D. Dr. Getz' group is studying the role of apolipoproteins E and A-I in atherosclerosis and Alzheimer’s disease by structure function analysis in cell culture and genetically modified mice. The removal of the apoE gene in mice results in profound hyperlipoproteinemia causing severe atherosclerosis that closely resembles that seen in man. Mice doubly deficient in apoE and the recombination activation gene (RAG2) have reduced plasma cholesterol and triglyceride levels and less atherosclerosis in some vascular sites. Similarly mice deficient in both LDL receptor and RAG2 have less hyperlipoproteimia and less atherosclerosis. Dr. Getz is using these models to explore the effects of the immune system on both plasma lipoproteins and atherosclerosis, by adoptive transfer experiments and cytokine administration.

Dr. Getz's laboratory has demonstrated that ? amyloid, the protein that accumulates in the brain of Alzheimer’s patients, forms a stable complex with apoE2 and E3 and not E4, perhaps facilitating the clearance of the ? amyloid. They are now studying the effect of apo E containing lipoproteins on the repair of experimentally injured mouse hippocampus, the primary focus of pathology in Alzheimer’s disease.
Somatic gene transfer is being used to express phosphoenolpyruvate carboxykinase, the major enzyme involved in hepatic gluconeogenesis and thus producing hyperglycemia and hyperinsulinism, as observed in diabetes mellitus.

Theodore Karrison, Ph.D. 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 GCRC, 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. 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.

The experimental approach combines X-ray crystallography and biophysical analyses with the power of phage display mutagenesis. The feasibility of each research area is established through preliminary studies. The primary structure data will be obtained by solving prolactin and variant growth hormone receptor complexes. Crystals and data for two systems have been obtained. As a long-range goal, to assess the capabilities of conformational versatility, structural analyses will be used and the extensive molecular diversity available from phage display to explore the stereochemical limits for binding solutions available to growth hormone-like molecules to the growth hormone receptor.

Rebecca Lipton, Ph.D., M.P.H., B.S.N. The overall goal of Dr. Lipton’s research is to understand the epidemiology, etiology and social implications of childhood diabetes, with particular reference to minority youth. Currently, her major project is a population-based incidence registry of diabetes in children ages 0-17. This study has led to clinical research in distinguishing early-onset Type 2 from more typical Type 1 diabetes as it occurs in children, as well as studies to determine correlates of early diabetes complications. The investigation of the role of genes in the etiology of autoimmune diseases of children, the determinants of health services utilization, diabetes-related mortality, and the family impact of pediatric chronic disease are major outgrowths of this research.

Ronald A. Thisted, Ph.D. 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.