T32 Training Program
The “Diabetes and Its Metabolic Complications” T32 Training Program at the University of Maryland Baltimore is a program designed to train predoctoral students and postdoctoral fellows in physiology and pathophysiology related to diabetes at the molecular, cellular and organism levels. The program takes advantage of the multidisciplinary and highly interactive research environment at the University of Maryland School of Medicine and the Amish Research Clinic (Lancaster, PA) to provide outstanding training in critical areas of basic and translational research related to diabetes and its complications. A guiding philosophy is that the “Diabetes and Its Metabolic Complications” T32 training program will provide integrative activities that illuminate the inter-relatedness of basic research and clinical medicine. Support for the program has been provided from a training grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Major advances in our understanding of disease biology require a detailed understanding of the physiology and pathophysiology at the molecular, cellular, and integrated whole body level. The faculty of this training program is particularly strong in translational research including genetics, epidemiology, cell biology, clinical physiology, clinical pharmacology, and pharmacogenomics. In addition to areas directly related to physiology and pathophysiology of fuel metabolism, this program encompasses pathophysiology related to both macrovascular and microvascular complications of diabetes. Specific areas of interest include atherosclerosis, diabetic kidney disease, diabetic retinopathy, diabetic neuropathy, non-alcoholic steatohepatitis (NASH), diabetes-associated bone disease, and diabetic embryopathy. The goal of our training program is to provide an integrative research experience with appropriate mentoring and career guidance to prepare trainees for a career in diabetes research. The T32 “Diabetes and Its Metabolic Complications” program is designed to meet this objective through appropriate didactic and research components, interactive seminars and workshops, and professional development that should provide a solid foundation for a long term and successful career in diabetes research.
This T32 Training Program has positions for predoctoral students, postdoctoral fellows and for clinical fellows interested in research related to Diabetes and/or its Metabolic Complications. When applying for support from this training program, it will be important for candidates to articulate how the proposed training will prepare them for successful careers in diabetes research.
To be considered for a position on this training grant, a faculty mentor must first be identified and a research plan developed in conjunction with the mentor.
The award of a trainee slot on this grant is for a minimum of one year and a maximum of three years. Funding for the second and third years will be contingent upon demonstration of good progress during the prior year(s). Trainees and mentors are encouraged to apply for individual competitive fellowships or for other research grant support during their tenure in the program. All predoctoral and postdoctoral fellows supported by the “Diabetes and Its Metabolic Complications” T32 training program will participate in didactic components, interactive seminars and workshops, and professional development as appropriate to their background, in order to provide a solid foundation for a long term and successful career in diabetes research.
Funding support from this grant is limited to the levels mandated by NIH guidelines. For MD trainees, support from the T32 Training Program provides ‘protected time’ for immersion in research, and it is required that patient care responsibilities will be limited to <10% effort (one half day per week), primarily to help complete long-term patient care experience necessary for their subspecialities and to maintain patient-care skills.
Qualifications for Trainee Slots:
- All appointments to this training grant are restricted to U.S. citizens, legal permanent residents of the U.S. and noncitizen nationals. Persons on temporary or student visas are not eligible.
- Applicants must be committed to research related to diabetes and/or metabolic complications of diabetes.
- Predoctoral applicants must be enrolled in the Graduate Program In Life Sciences (GPILS; PhD or MD/PhD program) at the University of Maryland Baltimore. Students must have completed their coursework and be positioned to embark upon their thesis research.
- Postdoctoral applicants must have completed doctoral level training (e.g. PhD, MD, MD/PhD, PharmD, DDS or equivalent). Evidence of scholarly productivity in the form of publications or planned publications is required for trainees with PhD degrees and is highly desirable for trainees with MD degrees. Post-doctoral trainees from Clinical Fellowship training programs (e.g. Endocrinology, Nephrology, Gastroenterology, or Cardiology) are encouraged to apply.
- All applicants must identify a Faculty Mentor to sponsor their application. Ordinarily, the mentor would be selected from the list of Faculty Mentors formally associated with this T32 Training Program. However, with the approval of the Program Director (Simeon Taylor, MD, PhD), other mentors may be acceptable. In any case, the research project must be directly related to Diabetes and/or Metabolic Complications of Diabetes.
|Yen-Pei (Christy) Chang, PhD||Dr. Chang’s lab starts with linkage or association evidence from population-based data to identify genetic loci that play a role in complex diseases. Current phenotypes of interest are essential hypertension, high cholesterol, and other risk factors for developing diabetes-related complications.Another focus of Dr. Chang’s lab is to understand regulatory elements (non-protein coding) in the human genome. Using bioinformatics tools and a wide range of function prediction algorithms, her lab investigates predicted regulatory events that alter disease susceptibility with a variety of molecular tools. These regulatory elements include those involved in transcriptional enhancers, alternate promoters, alternate splicing, and alternative polyadenylation.|
|Stephen Davis, MBBS||Dr. Davis’ research focuses on physiological mechanisms that defend against hypoglycemia, and has identified promising therapeutic interventions to protect against the risk of hypoglycemia.In addition, Dr. Davis’ research investigates mechanisms that increase the risk of heart attacks and strokes in diabetic patients.|
|Claire Fraser, PhD||Structure and function of the human gut microbiotaPathogen diversity and evolutionHost-pathogen interactionsMicrobila forensics|
|Braxton Mitchell, PhD, MPH||Dr. Mitchell’s research program utilizes a variety of approaches to dissect genetic and environmental determinants of a variety of complex diseases, including type-2 diabetes and obesity. The goal of these efforts is to detect and identify common gene variants that influence disease susceptibility and to determine how these variants interact with lifestyle factors to influence disease risk.Much of Dr. Mitchell’s research is carried out in large population studies and includes collaborations with clinicians, molecular biologists, and geneticists.|
|Toni Pollin, PhD, MS||Dr. Pollin’s research uses statistical methods to identify both genetic and environmental factors causing common complex diseases, including type-2 diabetes and cardiovascular disease.In a genome-wide association study of participants in the Heredity and Phenotype Intervention (HAPI) Heart Study, Dr. Pollin identified a nonsense mutation in the APOC3 gene that improves plasma lipid profiles and decreases prevalence of coronary artery calcification.Dr. Pollin participates in collaborations to perform association studies in approximately 50 candidate genes in Diabetes Prevention Program participants. By identifying genetic variants associated with responses to interventions, this will enhance the ability to predict, prevent and treat type-2 diabetes.Dr. Pollin also conducts research to (1) assess the prevalence of a mongenic form of diabetes called Maturity Onset Diabetes of the Young (MODY) in a diabetes clinic population and in women with gestational diabetes, and (2) evaluate the utility of clinical testing for MODY in these populations.|
|Sanjay Rajagopalan, MBBS||Dr. Rajagopalan’s major research interests lie in the role of Type 2 diabetes (T2D) as a facilitator of cardiovascular disease.There are three major themes in Dr. Rajagopalan’s laboratory: Environmental Determinants of Cardiometabolic Disease, Inflammatory Mechanisms in Diabetes-Related Cardiometabolic Disease and Immune Mechanisms involved in Hypertension. There is substantial expertise in the laboratory on incretin action, particularly in the cardiovascular and immune systems. The techniques used in the laboratory include physiologic tools in mice to assess whole body insulin sensitivity, intra-arterial blood pressure and telemetry, live adipose imaging using confocal techniques and classic physiologic evaluation of micro and macrovascular function. The laboratory also works closely with the Mid-Atlantic NORC on adipose samples in humans and peripheral blood samples. Finally, the laboratory has access to a whole body exposure chamber that allows investigation of air pollution using concentrated ambient atmospheres that mimic high pollutant levels in many cities across the globe.Dr. Rajagopalan’s laboratory has also helped facilitate the development of novel imaging methods to evaluate atherosclerotic plaque in humans using magnetic resonance imaging (MRI) and is currently working on multiple trials usingAn emerging area in the laboratory is a partnership with Radiology to develop metabolic imaging methods using C13-hyperpolarized spectroscopy to enable metabolic imaging in cardiovascular tissues as well as other metabolically active organs.|
|E. Albert Reece, MD, PhD, MBA||Dean Reece’s research focuses on diabetes in pregnancy, birth defects and prenatal diagnosis.His research laboratory team investigates bio-molecular mechanisms of diabetes-induced birth defects, and has identified specific cytoarchitectural changes at the epithelial level of the cell associated with these anomalies. Biochemical changes include depletion in membrane lipids and phospholipids as well as excess free radicals.His group is now studying the molecular mechanisms, and methods to prevent these anomalies. He and his colleagues have also developed the technique of embryofetoscopy for early prenatal diagnosis and eventually for curative fetal therapy.|
|James Russell, MB, ChB, MS||Dr. Russell’s laboratory investigates the mechanisms and treatment of diabetic neuropathy. His laboratory is interested in developing strategies to decrease oxidative and excitotoxic stress in neurons and Schwann cells.The laboratory examines pathways of oxidative and mitochondrial injury in the peripheral nervous system, and mechanisms to prevent or reverse cellular injury. Understanding these basic mechanisms of glucose-induced injury in the peripheral nerveOther research in the laboratory includes examining mechanisms of axonal growth and myelination in peripheral neuropathy. This translational research is aimed at developing improved diagnosis and treatment for peripheral neuropathies.Dr. Russel’s group participates in the “Improving Neuropathy and Mobility in Early Diabetes” (INMED) study. This blinded study aims to determine if a personally tailored diet and physical exercise program will improve neuropathy in patients with early diabetes.|
|Alan Shuldiner, MD||Dr. Shuldiner’s major research interests lie in genetics of age-related diseases, including type 2 diabetes (T2D), obesity and cardiovascular disease – common disorders of aging that contribute significantly to mortality, morbidity and health care costs in the United States and world-wide.Dr. Shuldiner is best known for his studies in the Old Order Amish, a homogeneous founder population ideal for genetic studies. He leads a large multidisciplinary research team that uses state-of-the-art molecular genetic, statistical and epidemiological methods, including both candidate gene and genome-wide approaches. More recent genome-wide association studies (GWAS) in the Amish have uncovered novel mutations that have informed human biology and population genetics.Dr. Shuldiner’s group is also a leader in the field of pharmacogenomics. They are best known for identifying a gene variant in CYP2C19 that is associated with poorer response to clopidogrel (Plavix). These findings contributed to FDA’s decision to mandate a boxed warning on the prescribing information recommending CYP2C19 genetic testing to individualize anti-platelet therapy for patients undergoing coronary interventions and for patients with acute coronary syndromes.|
|Dudley Strickland, PhD||Dr. Strickland’s research focuses on the low density lipoprotein (LDL) receptor-related protein (LRP) in cell signaling and disease biology. LRP is a large cellular receptor that not only functions as an important cargo transporter, but also informs cells of environmental changes. LRP is a member of the LDL receptor superfamily, and binds 30 or more ligands. Cargo transport by LRP is closely associated with regulation of cellular physiology and cellular signaling events.Role of LRP in atherosclerosis. Smooth muscle cells play an important role in the maintenance of vessel wall integrity, and undergo proliferation in response to injury. Interestingly, a role for LRP in smooth muscle biology was established some time ago, when it was demonstrated that LRP antibodies inhibited smooth muscle cell migration. Recent studies have found that LRP is atheroprotective, and prevents proliferation of smooth muscle cells in response to injury. This occurs by regulation of platelet derived growth factor (PDGF) receptor. PDGF induces transient tyrosine phosphorylation of the LRP cytoplasmic domain, and may have important consequences in PDGF-initiated signaling. Studies are underway to elucidate the role of LRP in modulating PDGF signaling.Role in inflammation. Chronic inflammation is a key feature of atherosclerosis. During the development of this disease, monocytes are recruited to the vessel wall where they differentiate into macrophages and greatly accelerate plaque formation and the progression of this disease. Many ligands recognized by LRP are generated during inflammation and/or wound repair, which has led us to hypothesize that LRP functions to modulate the inflammatory response, and Dr. Strickland’s laboratory is investigating this hypothesis by studying the role of LRP in macrophages.|
|Simeon Taylor, MD, PhD||Genetics of metabolic disease including type 2 diabetes and obesity. Dr. Taylor’s research focuses on identifying genetic variants in the coding sequences of genes that are associated with metabolic disease in the Old Order Amish. The research aims to elucidate the functional impact of the amino acid substitution on protein function, and also to illuminate the role of the protein in human biology.Pharmacogenomics of anti-diabetic drugs. While working in the pharmaceutical industry, Dr. Taylor had a role in R&D leading to four approved drugs (saxagliptin, dapagliflozin, metreleptin, and apixaban). His NIH-supported pharmacogenomics research is directed toward identifying genes that determine the response to SGLT2 inhibitors – the newest class of oral antidiabetic drugs.|
|Paul Welling, MD||Molecular genetics and physiology of electrolyte transport disorders. The movement of ions across cell membranes is exquisitely controlled for a diverse variety of vital body functions. Defects in ion transport molecules and their regulators give rise to serious, even lethal, human diseases. A major thrust of investigations in the Welling laboratory involves molecular genetic dissections of inherited disorders of membrane transport, so-called “channelopathies” or “transporteropathies.”Dysregulation of transport molecules in human disease. Dr. Welling employs a multidisciplinary approach, combining tools of molecular genetics, cellular biology, biochemistry, and physiology with state-of-the-art imaging techniques. A key strategy involves defining regulator or localization signals that are embedded within the structures of ion channels and salt-transporters; discovering the intracellular machinery that decodes the signals; and understanding the molecular signaling pathways that influence the interaction between the two. Genetically modified animal models are used to translate discoveries about fundamental mechanisms to higher-level systems in vivo.Regulation of potassium channels in the heart, kidney and nervous system in health and disease. Dr. Welling is focused on translating understanding of fundamental molecular mechanisms to directly impact therapy of human disease. One research program is focused on mechanisms that control salt balance and blood pressure in health and contribute to electrolyte disorders and hypertension in kidney disease. Studies in the heart have potential to provide a molecular understanding of certain hereditary arrhythmias.|
|Peixin Yang, PhD||Dr. Yang’s research focuses on investigations of maternal diabetes-induced embryonic vasculopathy and cardiovascular defects. Dr. Yang has extensive experience with transgenic mice and his lab refined the in vitro whole-conceptus culture system and the in vivo diabetic pregnant mouse model to demonstrate critical involvement of JNK/iNOS/HIF-1/SOD1/PKC lipid peroxidation pathways in induction of diabetic embryonic vasculopathy.|
|Zhekang Ying, PhD||Dr. Ying’s research investigates the mechanisms whereby ambient particulate matter pollution induces insulin resistance with a focus on the role of central nervous system (CNS). Dr. Ying trains students and fellows in airborne particulate matter exposure using a state-of-art whole-body exposure system that mimics real-world exposure to air pollution, and state-of-art CNS function analysis technologies such as intracerebroventricular and intranuclear injection and CNS morphological analysis.|
|Norann Zaghloul, PhD||Defects in genes associated with primary cilia. Ciliopathies are present in a spectrum of disorders including certain forms of obesity and diabetes. Dr. Zaghloul uses a zebrafish model in addition to various cell and molecular techniques to investigate the role of cilia in regulating the Notch signaling pathway as a contributor to pancreatic beta cell function.Functional genomics of diabetes. Dr. Zaghloul has pioneered a novel approach to complex problems in the pathophysiology and functional genetics of diabetes. Recently, she has adapted the zebrafish model for high-throughput drug screens of agents that enhance beta cell proliferation and insulin secretion. This approach provides a valuable perspective on developmental aspects of diabetes by applying model systems to understand mechanisms underlying human diabetes genetics.|