2008 T. Franklin Williams Scholar Recipients

George C. Wang, MD

“Immunologic Dysregulation and Inflammation in the Pathogenesis of Frailty of Old Age: The Role of CMV Infection”

Johns Hopkins University School of Medicine

Dr. George C. Wang is Instructor of Medicine in the Division of Geriatric Medicine and Gerontology, Department of Medicine, at the Johns Hopkins University School of Medicine. He is trained in internal medicine and geriatric medicine, and is currently pursuing a PhD in Clinical Investigation. His main research interests include the elucidation of immunologic changes of aging and the pathogenic immunologic mechanisms underlying age-related diseases and frailty in older adults, and the translation of this knowledge to the improvement of older adults’ health. Dr. Wang received a B.S. in Biomedical Engineering from Johns Hopkins University, with honorary membership in the Tau Beta Pi National Engineering Honor Society, and obtained his medical degree from the State University of New York Downstate College of Medicine. After completing an internal medicine residency at the University of Medicine and Dentistry of New Jersey, he trained with Dr. Knight Steel in a clinical geriatrics fellowship at the same institution. He then joined the Division of Geriatric Medicine and Gerontology at Johns Hopkins as a research fellow, concurrently pursuing rigorous training in JHU’s Graduate Training Program in Clinical Investigation, jointly sponsored by the Schools of Medicine and Public Health. His T. Franklin Williams project focuses on the role of cytomegalovirus infection in the pathogenesis of frailty and immunologic alterations in older adults.

Research Abstract

2008 T. Franklin Williams Scholar 2008
George C. Wang, MD

Frailty in older adults is associated with immunologic dysregulations and a systemic inflammatory state. In chronic inflammatory conditions and infectious diseases, the T-cell receptor (TCR) repertoire becomes increasingly restricted as oligoclonal T cells accumulate. Because latent cytomegalovirus (CVM) infection has been shown to be associated with frailty, we have now hypothesized that in a subset of humans who eventually become frail, latent CMV infection leads to a chronic inflammatory state and, perhaps through frequent reactivation, cause an accumulation of CMV-specific T cells and restriction of the TCR diversity. Further more, we hypothesize that, regardless of CMV’s role in frailty, an accumulation of senescent memory T cells and concomitant restriction in TCR diversity are associated with frailty. These immunologic dysregulations could play important roles in the pathogenesis of frailty. To test these hypotheses, we propose the following aims:

Specific Aim 1. To determine the relationships between T-cell phenotype alterations, CMS-induced immunologic parameters, and TCR diversity and frailty, in a cross-sectional case-control study (N=194) within the Women’s health in Aging Study (WHAS).

Specific Aim 2. To determine whether the frequency of CMV reactivation is associated with frailty, by measuring CMV viral load in repository samples from multiple time points.

Specific Aim 3. To determine whether the immunologic alterations identified above antecede the onset of frailty, by performing a nested case-control study (N=194) using longitudinal data in WHAS. We will develop a model based on these parameters to predict the development of frailty.

The long-term objectives of this research plan are to identify potential targets along the pathophysiologic pathway of frailty that are amenable to preventive and therapeutic interventions, and enable clinicians to identify at an early stage those older adults most vulnerable to develop frailty so that a preventive program can be started before the onset of frailty.

 

 

The recipient, selected by an academic selection committee composed of nationally prominent academic physicians, will receive a $75,000 grant over a two-year period. The award must be matched by support (either from the applicant’s home institution or a grant-making agency) that provides for 75% protected time for research. Research findings are presented at the American Geriatrics Society Annual Scientific Meeting at the conclusion of the recipient’s grant.

 

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