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Department of Medicine

Department of Medicine

  Division of Endocrinology and Metabolism

RESEARCH



Research Programs


DELANY RESEARCH PROGRAM

Dr. DeLany’s research interests include 1) the study of in vivo energy and substrate metabolism with the application of stable isotope methodologies as they relate to obesity and diabetes; 2) understanding the relationship between skeletal muscle characteristics, mitochondrial function, substrate utilization, body composition, and insulin sensitivity; and 3) examining metabolic factors related to the increased risk of obesity and diabetes in African-American women. Dr. DeLany also directs the EMRC Mass Spectrometry Core Laboratory.

 

 

James Delany, PhD
Principal Investigator

 

HORWITZ RESEARCH PROGRAM

Dr. Horwitz is a clinical metabolic bone researcher with a primary interest in the interaction of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) on mineral homeostasis, the skeleton, and vitamin D metabolism. This work has evolved to include NIH-sponsored clinical studies in osteoporosis, humoral hypercalcemia of malignancy, and hyperparathyroidism as well as lactation and its calcitropic/skeletal biology in both Caucasians and African-Americans. Dr. Horwitz has also collaborated on numerous osteoporosis and epidemiology studies with epidemiologists at the University of Pittsburgh Graduate School of Public Health.

 


Mara Horwitz, MD
Principal Investigator

 

JURCZAK RESEARCH PROGRAM

Dr. Jurczak’s lab is primarily interested in the relationship between nutrient excess, mitochondrial overload, and the pathogenesis of metabolic diseases, such as fatty liver, insulin resistance, and type 2 diabetes. Mitochondrial dysfunction and ectopic lipid accumulation in liver are both associated with insulin resistance in human subjects, but the cause and effect nature of these associations remain unclear. Dr. Jurczak’s lab is specifically interested in a mitochondrial repair mechanism called mitophagy that regulates the selective removal of damaged mitochondria via the autophagosomal pathway. Because autophagy is suppressed in mouse models of obesity and fatty liver disease, it is likely that mitophagy is similarly impaired and may contribute to the decline in mitochondrial function seen in human patients. Interestingly, a key component of the mitophagy pathway, a ubiquitin E3 ligase called Parkin, is upregulated in liver of obese mice. This change may represent a compensatory response to remove damaged mitochondria from hepatocytes or result directly from the loss of autophagy. Dr. Jurczak’s group is using a genetic approach to test whether the loss of Parkin-mediated mitophagy in liver predisposes mice to mitochondrial dysfunction, ectopic lipid accumulation, and insulin resistance. The lab employs in vivo and ex vivo approaches in transgenic mouse models and specializes in using radioactive and stable metabolic isotopes to measure substrate turnover and flux.

 


Michael Jurczak, PhD
Principal Investigator

 

KERSHAW RESEARCH PROGRAM | Website

Dr. Kershaw's academic mission is to forward the understanding and treatment of obesity and related metabolic disorders by combining basic and translational research with clinical expertise. Obesity is a global public health threat that is frequently associated with additional metabolic abnormalities including insulin resistance, glucose intolerance, dyslipidemia, and hypertension (the metabolic syndrome). Together these abnormalities contribute to diseases affecting virtually every organ system. Dr. Kershaw's laboratory focuses on defining the mechanisms by which intracellular lipid metabolism (synthesis, storage, hydrolysis, and oxidation) contributes to obesity and associated metabolic disorders. Most recently, Dr. Kershaw's research efforts have focused on pathways of triacylglycerol hydrolysis (lipolysis) – arguably one of the most fundamental processes in metabolism. Dr. Kershaw is working to define how tissue-specific triacylglycerol hydrolysis contributes to metabolic phenotypes, not only in the metabolic syndrome, but also in variety of other diseases ranging from infertility to cancer. Another major focus of her laboratory is to identify and characterize additional proteins and pathways that contribute to metabolic disease. These efforts fall into two main areas: 1) characterizing novel adipocyte-secreted factors (adipokines) and their relationship to metabolic disease in humans, and 2) characterizing novel genes/loci linked to metabolic disease in humans. Dr. Kershaw's laboratory uses a combination of molecular, cellular, physiological, and translational approaches. The ultimate goal is to develop more effective strategies for prevention and treatment of obesity and associated metabolic disorders.

 


Erin Kershaw, MD
Principal Investigator

 

KORYTKOWSKI RESEARCH PROGRAM

Dr. Korytkowski’s research focuses on improving the inpatient and outpatient care of patients with diabetes. She is involved in both research and quality improvement initiatives related to inpatient management of diabetes.  She is the PI of a study that prospectively investigates how hypoglycemia in the inpatient setting can influence factors associated with hospital discharge and long-term follow-up. She is a co-investigator and the study physician for the NIH sponsored Look AHEAD Study (Action For Health in Diabetes), which examined the effects of intensive lifestyle interventions with diet and exercise on long-term macrovascular complications. She is a co-investigator on three other NIH studies, one investigating the interactions between treatment for obstructive sleep apnea and diabetes outcomes, and two that investigate the contribution of social support to outcomes in adults with type 1 and type 2 diabetes.

 


Mary Korytkowski, MD
Principal Investigator

 

O’DOHERTY RESEARCH PROGRAM

Dr. O’Doherty’s research is focused understanding the biochemical and molecular mechanisms that link obesity, insulin resistance, dyslipidemia, and inflammation in the metabolic syndrome. Current efforts focus on the mechanistic relationship between steatosis and insulin resistance and the role of increased activity of the innate immune system/inflammatory pathways in the pathogenesis of insulin resistance in obesity. Dr. O'Doherty is Director of the Center for Metabolism and Mitochondrial Medicine (C3M), Metabolism Unit.

 

 


Robert O'Doherty, PhD
Principal Investigator

 

SIMINERIO RESEARCH PROGRAM

Dr. Siminerio’s focus is on diabetes health care delivery models, quality improvement, self-management, community interventions, and overcoming barriers to diabetes care in underserved populations. Her research is currently focused on translating diabetes treatment and prevention programs into community-based settings, such as the Patient Centered Medical Home. Dr. Seminario serves as Chair of the International Diabetes Federation’s Building Research in Diabetes Global Environments and Systems (BRIDGES) translational research program.

 


Linda Siminerio, RN,
PhD, CDE

Principal Investigator

 

TOLEDO RESEARCH PROGRAM

Dr. Toledo’s clinical and translational research lab is focused on understanding the etiology of diabetes in humans and developing new treatments. His research program is specialized in the measurement of human metabolism in vivo and employs state-of-the-art methodologies such as euglycemic clamps, IVGTTs, stable-isotope tracer methods to measure lipid and glucose metabolism in vivo, indirect calorimetry, and muscle and fat biopsies. Dr. Toledo’s studies have focused on understanding the complex relationships between mitochondrial energetics, morphology, and the development of insulin resistance in diabetes and obesity. He has pioneered studies demonstrating the specific effects of weight loss and exercise on mitochondria in the context of diabetes and insulin resistance. Recently, Dr. Toledo has been investigating the effects of hydroxycholoquine and neutrophil elastase inhibition to develop new treatment strategies for disordered glucose metabolism in humans. Dr. Toledo has also been the PI of pioneer studies demonstrating the feasibility and clinical outcomes of videoconferencing Telemedicine consults to deliver diabetes care remotely. Dr. Toledo is the Clinical Research Director of the Center for Metabolic and Mitochondrial Medicine.


Frederico Toledo, MD
Principal Investigator