Eugenia Wang, PhD
by Kathleen H. Sauer — last modified May 18, 2009 11:34 AM
Email Dr. Eugenia Wang
Address: 580 S. Preston St., Baxter II, Rm 102
PhD, 1975, Case Western Reserve University
Research Interests: Genetic mechanisms of Aging
The focus of my laboratory is to study the genetic mechanisms determining the biology of the healthy aging process, and the molecular culprits that derail this process and result in age-dependent diseases. Several projects are ongoing, investigating: 1. why normal human fibroblasts have finite in vitro life span, reaching replicative senescence with permanent growth arrest, losing their apoptosis-resistant phenotype. Our hypothesis is that transcriptional repression of the expression of pro-cell growth genes prevents cell cycle traverse. We have identified a transcriptional repressor, hMad4, functionally competing with cMyc for transcripttional activation. Experiments are in process to knock down this gene expression, and determine whether replicative senescence can be delayed; 2. the significance of a developmental switch between two sister proteins of a translation elongation factor family. We have identified a unique translation elongation factor, eEF1A2, a sister gene of the more familiar eEF1A1 (EF1-), expressed only in neurons, cardiomyocytes, and myotubes. Experiments are underway to investigate the molecular partners of both genes, and whether they change identity during aging in young and old mice; 3. unique single nucleotide polymorphisms (SNPs) segregating with nonagenarians and centenarians, specifically genes responsible for robust oxidative defense; and 4. using cells derived from extremely long-lived mutant mice to identify unique genomic and proteomic profiles of host response, rendering them at low risk for environmental insults. We are also using space-flown biological specimens to identify shared gene expressions between aging on earth and microgravity travel. Pursuing these gene-directed programs, controlling cellular as well as organismic longevity, involves integrating diverse cutting-edge technologies including microarray gene signature profiling, RNAi knockdown, yeast two-hybrid, proteomics, bioinformatics, and applying pattern recognition to datamining. Our ultimate goal is to gain quantum understanding of how healthy life span is maintained, and to generate enabling therapeutic technology to minimize, ameliorate, and eliminate age-dependent debility, frailty, and degeneration.
Selected Publications:Khalyfa, A., Bourbeau, D., Chen, E., Petroulakis, E., Pan, J., Xu, S., and Wang, E. Characterization of elongation factor-1A (eEF1A-1) and eEF1A-2/S1 protein expression in normal and wasted mice. J. Biol. Chem. 276(25): 22915-22922 (2001).
Lacelle, C., Xu, S., and Wang, E. Identification of high caspase-3 mRNA expression as a unique signature profile for extremely old individuals. Mechanisms of Ageing and Development 123: 1133-1144 (2002).
Semov, A., Marcotte, R., Semova, N., Ye, X., and Wang, E. Microarray analysis of E-Box binding-related gene expression in young and replicatively senescent human fibroblasts. Analytical Biochemistry 302: 38-51 (2002).
Semov, A., Lacelle, C., Semova, N., Marcotte, Petroulakis, E., Prestou, G., and Wang, E. Alterations in TNF and IL-related gene expression in space flown WI38 human fibroblasts. FASEB Journal (April 23) 10:1096/fk/01-1002fje (2002).
Marcotte, R. Qian, J. F., Wang, X. L., and Wang, E. hMad4, cMyc endogenous inhibitor, regulates apoptosis at two different levels of the mitochondrial apoptotic cascade. Journal of Cellular Chemistry 89: 576-588 (2003).
Thomas E. Geoghegan
Russell A. Prough
Christine Schaner Tooley
James L. Wittliff