General Research Themes – Research in the Houmard lab has primarily focused upon mechanisms in skeletal muscle that contribute to insulin resistance in skeletal muscle under the conditions of aging, obesity, and type 2 diabetes and how exercise training (resistance- and endurance-oriented) can correct and/or overcome these insulin-resistant conditions. Research in these areas has examined the roles of the insulin-sensitive glucose transporter (GLUT4), insulin signaling, lipid oxidation and storage, and other facets of general metabolism.  

Current Projects

• Lipid Metabolism in Obesity, Weight Loss and Exercise
  The purpose of this study is to determine what promotes the accumulation of lipid in the skeletal muscle of obese subjects and if exercise or weight loss can reverse this defect.  This is an NIH-funded project (2001 to 2011)with Dr. Houmard as the Principal Investigator.
  

• Age-related insulin resistance, muscle, and exercise
  The purpose of this grant is to determine if the accumulation of lipid within skeletal muscle is associated with insulin resistance in aged individuals.  This is an NIH-funded project (2005 to 2010)with Dr. Houmard as the Principal Investigator.

• Peripheral Effects of Exercise on Cardiovascular Health
  The purpose of this study is to continue to investigate the biological mechanisms through which chronic physical activity alters carbohydrate metabolism and lipid metabolism resulting in improvements in these parameters of cardiovascular health and fitness in humans.  The focus of the continuation project will be on a) resistance training and b) gene array analyses.  This is a collaborative effort with Duke University with Dr. Houmard as a co-investigator and has been ongoing from 1999 to 2009.

General Research Themes – Research in the Gavin lab currently focuses on two areas: 1) mechanisms for diabetes reversal following bariatric surgery; and 2) mechanisms for exercise intolerance in peripheral arterial disease (PAD).  Past research by our collaborators has shown that gastric bypass surgery is very effective in providing long-term reversal of diabetes; however the mechanisms for this reversal are difficult to partition between weight loss, food restriction, and foregut bypass.    

Current Projects

• Treatment of diabetes by duodenal-jejunal bypass.
  The purpose of this work is to determine: 1) if bypassing of the duodenum and proximal jejunum without weight loss or food restriction can successfully reverse diabetes; and 2) is this reversal in diabetes due to improvements in skeletal muscle insulin sensitivity, liver insulin sensitivity, and pancreatic insulin secretion.
  

• Limitations to exercise in PAD.
  The purpose of this work is to identify the mechanisms in PAD that: 1) contribute to exercise intolerance; and 2) are responsible for improvements in exercise tolerance in response to exercise training.

General Research Themes - Significant skeletal muscle wasting with age can result in lost functional independence, and interventions such as resistance exercise training are not fully effective in restoring muscle mass in elderly individuals.  Research in the Gordon lab is attempting to identify hormonal and/or molecular mechanisms of skeletal muscle remodeling with aging, disuse, and overloading/resistance exercise, especially with respect to the muscle’s ability to synthesize new proteins that comprise the muscle cells.

Current Projects

• “Aging, AMP Kinase, and Skeletal Muscle Overload”.
  The purpose of this project is to examine the mechanisms by which the enzyme AMP kinase (which is elevated in aging muscle and likely acts to suppress protein synthesis) may underlie the atrophy and/or the diminished capacity for growth that both occur predominantly in fast-twitch muscle fibers with age.  This work is supported by a grant from the National Institutes of Health through 2008.
  

• "Targeted Rescue of Protein Translation and Synthesis in Aged Skeletal Muscle”.
  The Purpose of this project is to determine if protein synthesis and growth in aging skeletal muscle can be rescued by blocking the activity of AMP kinase, and is supported by a grant from the American Federation for Aging Research through 2008.

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.   

Current Projects

• 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.

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.  

Current Projects

• “Mitochondrial-Peroxisomal Fatty Acid Oxidation in Obesity.”
  The purpose of this research is to establish a role for peroxisomes in facilitating the oxidation of long-chain fatty acids by skeletal muscle mitochondria in the obese state. National Institutes of Health (1 R15 DK061314-01 A2: 2003 to 2007) with Dr. Cortright as Principal Investigator.
  

• “Dysregulation of Fatty-Acid Metabolism in Skeletal Muscle in African-American and Caucasian Women.”
  The purpose of this research is to identify the cellular sites of dysregulated fatty acid oxidation in the skeletal muscle of African American vs. Caucasian women. National Institutesof Health (1 R21 DK065183-01: 2003 to 2007) with Dr. Cortright as Principal Investigator.
  

• “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 2010) with Dr. Cortright as Principal Investigator.

General Research Themes – Mitochondria are known as the “powerhouse” of the cell, converting metabolites into a useable form of energy for the rest of the cell.  In skeletal muscle, inactivity and obesity lead to a profound loss of mitochondrial function while exercise training enhances mitochondrial functional capacity.  Research in the Neufer lab is directed at deciphering the molecular mechanisms regulating mitochondrial function in the context of both metabolic disease as well as disease prevention/treatment.

Current Projects

• Mitochondrial bioenergetics and etiology of insulin resistance.
  The purpose of this research is to determine if the loss of mitochondrial integrity and insulin sensitivity stem from a common metabolic disturbance, i.e., oxidative stress.  The projects utilize a newly developed permeabilized fiber approach to study mitochondrial function in rodent skeletal muscle, pharmacological agents and transgenic models to manipulate mitochondrial ROS production and scavenging. National Institutes of Health (NIH RO1 DK073488-01: 2007-2111) with Dr. Neufer as Principal Investigator.
  

• Linking mitochondrial bioenergetics to insulin sensitivity.
  The purpose of this project is to examine the potential link between mitochondrial function/dysfunction and insulin sensitivity in 1) obese humans 2) younger subjects of normal weight and with normal insulin sensitivity acutely exposed to high caloric/high fat diet; and 3) in obese subjects undergoing a diet/exercise intervention to reverse insulin resistance.