South Texas Veterans Health Care System (STVHCS)
Alfred Fisher, MD, PhD
Associate Director for Research
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Led by Alfred Fisher, MD, PhD, Associate Director for Research, the San Antonio GRECC has an active research program devoted to developing newer and better ways to improve the health and quality-of-life of older Veterans. Our research is focused on gaining a better understanding of the basic mechanisms of aging, as well as the pathophysiology of metabolic and inflammatory conditions that affect the lives of millions of aging Veterans.
Our current research focus is centered on two broad themes: Metabolism and Inflammation. Individual projects focus on diabetes, diabetic nephropathy, nonalcoholic liver disease, frailty, sarcopenia, Alzheimer‘s disease, Lewy body disease, ALS, Parkinson‘s disease, cancer, and salivary hypofunction. The projects described below are currently underway and aimed at understanding the basic biology of aging, the mechanisms regulating longevity, and the pathophysiology of age-related diseases.
Current Research Projects
- Diabetes, Obesity, and Molecular Effects of Exercise: Drs. Nicolas Musi has several ongoing projects focused on the cellular and molecular basis for age-related changes in glucose and lipid metabolism and the pathogenesis of insulin resistance and sarcopenia in aging and diabetes. These studies investigate how mitochondrial dysfunction, oxidative stress, and inflammation are involved in age-related alterations in glucose and lipid metabolism. Studies in Dr. Amrita Kamat’s laboratory focus on how excessive accumulation of fat in the liver impairs its function and is associated with the development of various components of the metabolic syndrome including non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus and cardiovascular diseases.
- Sarcopenia and Frailty: The loss of muscle mass that occurs during aging often leads to disability, decreased physical activity, and loss of independence. Sarcopenia also contributes to the pathogenesis of age-related diseases, such as diabetes. Ongoing studies in Drs Musi's laboratory investigate the role of increased oxidative stress and IKK/NFkB signaling in the pathogenesis of sarcopenia. Dr. Sara Espinoza is studying the pathophysiology of frailty using a comparative proteomic analysis of plasma glycoproteins. Finally, Dr. Dean Kellogg is studying how increased oxidative stress in aging has been implicated as a major factor in age associated impairments in both reflex and local skin vascular control mechanisms.
- Insulin/mTOR Signaling (Longevity Studies): The only manipulations currently shown to retard aging in mammals are caloric restriction and genetic mutation of the insulin and insulin growth factor (IGF)1 signaling pathway. However, these manipulations cannot be translated easily to humans. Thus, several ongoing projects in the laboratories of Drs. Randy Strong and Elizabeth Fernandez focus on the life extending effects of rapamycin.
- Inflammation and Neurodegenerative Disease: Inflammatory processes have been implicated in neurodegenerative disorders, such as Alzheimer‘s disease and Lewy body disease. The latter is particularly common among Veteran patients. Dr. Donald Royall has developed a research program largely directed toward improving the psychometric assessment of dementing illnesses. He is currently developing latent variables, derived from longitudinal as well as cross sectional data that can be used in the search for dementia-related biomarkers. Drs. Randy Strong and Elizabeth Fernandez are conducting studies in mice with reduced levels of Aldh1a1 and Gpx1 expression under conditions in which mitochondrial complex I is impaired, to determine if this will lead to the amplification and accumulation of reactive species and highly reactive biogenic aldehydes.
- Inflammation and Oral/Periodontal Disease: In an ongoing research collaboration with Rice University and Dr. Spencer Redding (Chair, Comprehensive Dentistry, UT Health Science Center), Dr. Chih-ko Yeh is developing a Lab-on-a-Chip multiplex diagnostic for acute myocardial infarction using saliva samples in pre-hospital settings (e.g., in ambulance) and for other diseases (e.g., oral and systemic cancers).
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