EDUCATION
I began my education at Oklahoma State University and subsequently attended Indiana University. Finally, in 1998, I graduated from Benedictine University in Lisle, Illinois. I entered the IDP at the University of Florida in August of 1998 and after the first year of the program chose to enter Dr. Clare-Salzler’s lab. My studies are being performed in collaboration with the Moldawer Laboratory in the Department of Surgery under the direction of Lyle Moldawer, PhD. The Moldawer laboratory studies sepsis and inflammation focusing particularly on the role of tumor necrosis factor-alpha (TNF-a).
MY STUDIES
Many investigators utilize recombinant mouse techniques to investigate complex immunologic processes. We proposed to examine TNF-a signaling by employing the endotoxin/Dgal model of hepatocyte apoptosis. Using recombinant inbred mice with differing sensitivities to endotoxin/Dgal treatment allows for quantitative trait loci analysis and dissection of potential mediators in the TNFa signaling pathway. Our goal is to identify regions in the genome of a resistant strain of mice responsible for protection from hepatocellular apoptosis and lethality. By breeding a resistant strain to a susceptible strain it is possible to phenotypically analyze the F1 heterozygotes for the trait of interest and determine whether it is dominant or recessive. Backcrosses can then be performed to systematically dilute the genome and obtain backcross progeny carrying various segments of their genome from either of the parental strains. Phenotypic analysis of these recombinant mice allows for statistical determination of the probable loci involved in the resistance or susceptibility. This approach should increase the likelihood of identifying novel genes involved in susceptibility and/or resistance to TNFa-dependent processes such as hepatocellular apoptotic injury and lethality. The importance of these studies to the field of septic shock and TNFa-mediated diseases is profound. Mortality rate due to septic shock has not improved in the past 50 years and current therapies for sepsis patients have not been successful despite their success in animal models. Thus, identification of new mediators in the TNFa pathway could provide new targets for therapy.
MANUSCRIPTS AND ABSTRACTS
Bahjat, K.S., F.R. Bahjat, D.S. Whittaker, T.Xie, E. Wakeland, T. Auffenberg, L. Moldawer and M.J. Clare-Salzler. (1999) Defect in AICD in the NOD mouse. Keystone Symposium: Autoimmunity and Tolerance, Keystone, Colorado
F. R. Bahjat, M. Clare-Salzler, L.L. Moldawer. (2000) Genetic determinants of TNFa mediated liver apoptosis. 5th World Congress on Trauma, Shock, Inflammation and Sepsis, Munich, Germany.
F.R. Bahjat, M. Clare-Salzler, L.L. Moldawer. (2000) Genetic polymorphisms in the response to lipopolysaccharide and d-galactosamine in the mouse. Surgical Infection Society, Providence, Rhode Island.
Josephs, M.D., Bahjat, F.R., Fukuzuka, K., Ksontini, R., Solorzano, C.C., Edwards, C.K. III, Tannahill, C.L., MacKay, S.L.D., Copeland, E.M. III, Moldawer, L.L. Lipopolysaccharide and D-galactosamine-induced hepatic injury is mediated by TNF-alpha and not by fas ligand. Am J Physiol (In Press).
Nowak, M., Gaines, G.C., Rosenberg, J., Minter, R., Bahjat, F.R., Rectenwald, J., MacKay, S.L.D., Edwards, C.K. III, Moldawer, L.L. Lipopolysaccharide-induced liver injury in D-galatosamine-sensitized mice requires secreted TNF-alpha and the TNF p55 receptor. Am J Physiol (In Press).
Rebecca M. Minter, Maria A. Ferry, F.R. Bahjat, Andreas Oberholzer, Caroline Oberholzer, Drake La Face, Van Tsai, Iqbal Ahmed, Beth Hutchins, Richard Moyer, Edward M. Copeland, III, Lyle L. Moldawer. Extended Lung Expression and Increased Tissue Localization of Viral IL-10 with Adenoviral Gene Therapy. PNAS (submitted Jan. 2000).