Joseph A. Houmard
General Research Themes - Research in the Houmard lab is currently focused upon discerning the underlying mechanisms for the decrement in fat oxidation in the skeletal muscle of severely obese individuals and how this defect is corrected with exercise. This work examines intact humans as well as primary human skeletal muscle cells derived from severely obese and lean donors. In a broader sense, work in the lab is focused upon conditions linked with obesity and insulin resistance and how exercise can counteract these conditions. Previous work has examined insulin signal transduction and aging as well as other general areas of skeletal muscle metabolism.
- Lipid Metabolism in Obesity, Weight Loss and Exercise – The purpose of this work is to determine why lipid oxidation is depressed in human skeletal muscle with obesity and how exercise training or weight loss via gastric bypass surgery serves as an effective intervention. This is an NIH funded project (2001 to 2016) with Dr. Houmard as the primary investigator.
- Physical Activity During Surgery-Induced Weight Loss – The purpose of this study is to determine if the addition of endurance-oriented exercise training additively improves risk factors for disease in gastric bypass patients compared to surgery alone. This is an NIH funded project which will continue through 2013 in collaboration with Bret Goodpaster at the University of Pittsburgh.
Robert C. Hickner
General Research Themes - Research in the Hickner lab has primarily focused upon how exercise and exercise training improve the regulation of blood flow and metabolism in skeletal muscle and adipose tissue in humans. A current focus is on the regulation of blood flow and metabolism by nitric oxide, and how alterations in this system impact on cardiovascular disease risk across the lifespan.
- Reduction of CVD risk in children through physical activity (UMCIRB# 05-0384) - The purpose of this study is to determine if physical activity can reduce the suppression of lipolysis (mobilization of fat stores) by nitric oxide, improve glucose profiles, and reduce CVD risk in 8-11 yr. old children. This is an NIH-funded project (1R01DK071081: 2006 to 2011) with Dr. Hickner as the Principal Investigator.
- Ethnic differences in the regulation of lipolysis by nitric oxide and adenosine (UMCIRB# 06-0257) - The purpose of this study is to determine if there are ethnic differences in the regulation of lipolysis (mobilization of fat stores) in adults due to nitric oxide or adenosine-mediated suppression of lipolysis. This is an NIH-funded project (1R15DK074401: 2006 to 2008) with Dr. Hickner as the Principal Investigator.
Ronald N. Cortright
General Research Themes - Research in the Cortright lab has primarily focused upon mechanisms in skeletal muscle that contribute to insulin resistance in skeletal muscle under the conditions of obesity, and type 2 diabetes and how exercise training (endurance-oriented) can correct and/or overcome these insulin-resistant conditions. Research in these areas has examined the roles of insulin signaling, lipid oxidation and storage, peroxisomal-mitochondrial interactions in substrate utilization and the implications in muscle bioenergetics and diseases, as well as other facets of general metabolism.
- Impaired Acyl-CoA Synthetase-Muscle Lipid Oxidation in African American Women (AAW) - The purpose of this research is to determine if the impairment in skeletal muscle fat oxidation in African-American Women (AAW) is due to a defect in acyl-CoA synthetase (ACC), the enzyme required for activating fatty acids prior to transport and oxidation in the mitochondria and whether AAW will respond to exercise training by increasing the capacity of skeletal muscle to oxidize lipids, due in part to a normalization of ACS activity. National Institutes of Health (1RO1DK075880-01: 2006 to 2012) with Dr. Cortright as Principal Investigator.
Carol A. Witczak
General Research Themes - Research in the Witczak lab is focused on determining the cellular and molecular basis underlying the beneficial effects of exercise on skeletal muscle metabolism. Specifically, the lab focuses on understanding the intracellular signaling mechanisms underlying exercise/contraction-induced skeletal muscle glucose uptake and muscle growth.
- Skeletal Muscle Growth: Skeletal muscle metabolic dysfunction and atrophy are prominent features of a number of devastating diseases, including diabetes and cancer. Intracellular Ca2+ is a key regulator of numerous processes in skeletal muscle, including growth, yet surprisingly the signaling mechanisms by which Ca2+ regulates these functions remain largely unknown. The goal of this study is to determine the role of the Ca2+/calmodulin-dependent protein kinase kinase a (CaMKKa) in the regulation of skeletal muscle growth and protein synthesis. This is an NIH-funded project (K99/R00 AR056298: 2008 to 2014) with Dr. Witczak as the Principal Investigator.
- Skeletal Muscle Glucose Uptake: Type 2 diabetes is a metabolic disorder characterized by impairments in insulin stimulated glucose uptake into skeletal muscle. Muscle contractile activity (exercise) can also stimulate glucose uptake into skeletal muscle, and importantly, the ability of exercise to increase muscle glucose uptake is not impaired in people with type 2 diabetes. The goal of this study is to determine the intracellular signaling pathways by which exercise stimulates glucose uptake into skeletal muscle. Understanding how exercise stimulates muscle glucose uptake on a cellular and molecular level may lead to the development of new pharmaceutical therapies for people with type 2 diabetes.
Jeffrey J. Brault
General Research Themes - Research in the Brault lab is focused on understanding the molecular mechanisms of skeletal muscle atrophy, with a long-term goals of identifying novel targets to slow or reverse this loss of muscle. A major experimental emphasis in on the use of cutting edge techniques to precisely control gene expression in individual muscle fibers or in cultured muscle cells.
- Atrophy resistance in the severely obese - The purpose of this study is to understand how skeletal muscle mass is controlled in the obesity. Surprisingly, severely obese individuals (BMI > 40) have greater skeletal muscle mass than the lean in spite of the obese individual’s robust production of myostatin, a myokine well known to induce muscle atrophy.
- Energetics of muscle atrophy - The purpose of this study is to determine the source of the energetic deficiencies typically found in atrophying muscles. The current focus is on the metabolic genes AMP deaminase and IMP dehydrogenase, which are highly induced in most, if not all, atrophying muscles. Together, these two enzymes control the size of total adenine nucleotide pool (ATP + ADP + AMP).
General Research Themes - Research in the Funai lab is primarily focused on the cellular handling of lipids in metabolic stress. The rise in obesity prevalence has led to a pandemic of metabolic diseases including diabetes. We utilize cell lines, genetically-modified mice and primary cells from human subjects to examine mechanisms whereby tissues develop and/or evade toxic effects of lipid flux. Our primary focus is in skeletal muscle, where exercise plays an intriguing role in balancing lipid deposition with oxidation. The laboratory is located in the East Carolina Diabetes & Obesity Institute in the 4th floor of East Carolina Heart Institute.
- Phospholipid biosynthesis: Phospholipids are building blocks for cellular organelles. The purpose of this work is to investigate relevance of phospholipid biology in pathogenesis of metabolic diseases. We generated genetically-modified mice that are absent in the enzymes of phospholipid biosynthesis in skeletal muscle. This is an NIH-funded project (7K01 DK095774, 2013 to 2017) with Dr. Funai as a Principal Investigator.
- Aberrant muscle lipidome in human obesity (UMCIRB# 14-0326): Skeletal muscle insulin resistance is an early and essential defect in the development of type 2 diabetes and other co-morbidities. Aberrant lipid metabolism is likely responsible for muscle insulin resistance. The purpose of this project is to conduct unbiased lipidomic and transcriptomic screening on insulin sensitive and insulin resistant muscle cells isolated from human biopsy samples, to generate candidate genes that promote altered muscle lipid flux in obesity. Grants submitted with Dr. Funai as a Principal Investigator.
General Research Themes - Metabolic physiological activities including feeding behavior, body weight homeostasis, and glucose metabolism are critically regulated by different types of neurons located in hypothalamus of brain. Our laboratory seeks to understand the basic molecular mechanisms underlying the metabolic syndrome, including obesity, insulin resistance, impaired glucose metabolism and non-alcoholic fatty liver disease regulated by central nervous system, and ultimately to develop effective and applicable preventive and treatment programs. To achieve this goal, we utilize a combination of mice genetic engineering techniques and biochemical approaches to investigate how central neurocircuits control food intake, energy expenditure and body weight homeostasis in response to exercise and diet. By understanding how neurons integrate diverse signals into consistent metabolic programs, we hope to identify the mechanisms by which integrated physiological processes are regulated and how these processes are disrupted in disease states.
- It is known that environmental changes such as over nutrition, High-fat diet (HFD) feeding, as well as lack of exercise induced hypothalamic dysfunctions causing and promoting obesity and diabetes. The proposed research seeks to determine the importance of exercise on hypothalamic neurons degeneration and neurogenesis, especially focus on the Hypothalamic Adult Neural Stem Cells (HaNSCs). Previous studies demonstrate that exercise increases hippocampal neurogenesis. We thus hypothesize that exercise is also essential for HaNSCs survival, proliferation and differentiation, contributing to the neurodegenerative mechanism of obesity and related diseases.
General Research Themes - Research in the Swift lab is focused on the effects of exercise training and particularly different exercise training programs on cardiometabolic risk factors and type 2 diabetes risk factors. The goal of the lab is to perform exercise research with both clinical and public health recommendations.
- Intervention of Exercise Training and Non-Exercise Physical Activity: Dr. Swift is the PI of a 4 year American Heart Association sponsored study (NCT02010060) evaluating the effects of exercise training and increasing daily lifestyle physical activity on central adiposity, weight, oral glucose tolerance and systemic inflammation. This study includes supervised aerobic exercise training in laboratory setting, and cognitive behavioral session with participants to increase physical activity (e.g. steps) outside of exercise training. The goal of the study is to evaluate the clinical effectiveness of this combined physical activity program compared to simply performing only aerobic exercise training.
Darrell P. Neufer
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