Andrew T Gewirtz, PhD

Epithelial Pathobiology
Immunology

Associate Professor
Pathology & Laboratory Medicine

Pathology Division(s):
Experimental Pathology

Email Address:
agewirt@emory.edu

Education:

B.S.   Physics State University of NY, Albany NY (Advisor :Ray Benenson), 1984 - 1988

Ph.D.   Biochem Boston Univ. Schl. of Med. Boston MA (Advisor : Liz Simons), 1992 - 1996

Research Interests:

- Intestinal Epithelium
The intestinal epithelium is one of humans major interfaces with the outside world. This interface is very heavily colonized with gram negative bacteria and yet permits absorption of life-sustaining nutrients while protecting the tissues below from microbial onslaught. In addition to serving as a highly selective barrier, the intestinal epithelium regulates immune cells, especially in response to pathogens. Specifically, we have shown that upon detection of ingested pathogens, the intestinal epithelium signals to both innate and adaptive immune cells to provide short and long term protection against the perturbing microbe. My research seeks to understand, at the molecular level, the bacterial-epithelial interactions that regulate such signaling to immune cells. Such bacterial-epithelial interactions are likely germane to both mucosal immunity and inflammatory bowel disease.

Honors / Awards:

Career Development Award, NIDDK, NIH, Bethesda, MD, 2000

National Research Service Award, NIH Bethesda MD, 1997

Deans Research Award, Boston University, Boston MA, 1996

Travel Award, American Society for Cell Biology, Bethesda, MD, 1995

Selected Publications:

Published and Accepted Research Articles -

Mrsny, R. J., A. T. Gewirtz, D. Siccardi, T. Savidge, B. P. Hurley, J. L. Madara, and B. A. McCormick. 2004. Identification of hepoxilin A3 in inflammatory events: a required role in neutrophil migration across intestinal epithelia. Proc Natl Acad Sci U S A 101:7421.

Gewirtz, A. T., Y. Yu, U. S. Krishna, D. A. Israel, S. L. Lyons, and R. M. Peek, Jr. 2004. Helicobacter pylori flagellin evades toll-like receptor 5-mediated innate immunity. J Infect Dis 189:1914.

Sitaraman, S., X. Liu, L. Charrier, L. H. Gu, T. R. Ziegler, A. Gewirtz, and D. Merlin. 2004. Colonic leptin: source of a novel proinflammatory cytokine involved in IBD. Faseb J 18:696.

Lin, P. W., P. O. Simon, Jr., A. T. Gewirtz, A. S. Neish, A. J. Ouellette, J. L. Madara, and W. I. Lencer. 2004. Paneth cell cryptdins act in vitro as apical paracrine regulators of the innate inflammatory response. J Biol Chem 279:19902.

Zeng, H., A. Q. Carlson, Y. Guo, Y. Yu, L. S. Collier-Hyams, J. L. Madara, A. T. Gewirtz, and A. S. Neish. 2003. Flagellin is the major proinflammatory determinant of enteropathogenic Salmonella. J Immunol 171:3668.

Yu, Y., H. Zeng, S. Lyons, A. Carlson, D. Merlin, A. S. Neish, and A. T. Gewirtz. 2003. TLR5-mediated activation of p38 MAPK regulates epithelial IL-8 expression via posttranscriptional mechanism. Am J Physiol Gastrointest Liver Physiol 285:G282.

Langston, H. P., Y. Ke, A. T. Gewirtz, K. E. Dombrowski, and J. A. Kapp. 2003. Secretion of IL-2 and IFN-gamma, but not IL-4, by antigen-specific T cells requires extracellular ATP. J Immunol 170:2962.

Agrawal, S., A. Agrawal, B. Doughty, A. Gewirtz, J. Blenis, T. Van Dyke, and B. Pulendran. 2003. Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol 171:4984.

Liu, X., L. Charrier, A. Gewirtz, S. Sitaraman, and D. Merlin. 2003. CD98 and intracellular adhesion molecule I regulate the activity of amino acid transporter LAT-2 in polarized intestinal epithelia. J Biol Chem 278:23672.

Buyse, M., L. Charrier, S. Sitaraman, A. Gewirtz, and D. Merlin. 2003. Interferon-gamma increases hPepT1-mediated uptake of di-tripeptides including the bacterial tripeptide fMLP in polarized intestinal epithelia. Am J Pathol 163:1969.

Kucharzik, T., A. T. Gewirtz, D. Merlin, J. L. Madara, and I. R. Williams. 2003. Lateral membrane LXA4 receptors mediate LXA4's anti-inflammatory actions on intestinal epithelium. Am J Physiol Cell Physiol 284:C888.

Wang, L., B. Walia, J. Evans, A. T. Gewirtz, D. Merlin, and S. V. Sitaraman. 2003. IL-6 induces NF-kappa B activation in the intestinal epithelia. J Immunol 171:3194.

Gewirtz, A. T., L. S. Collier-Hyams, A. N. Young, T. Kucharzik, W. J. Guilford, J. F. Parkinson, I. R. Williams, A. S. Neish, and J. L. Madara. 2002. Lipoxin a4 analogs attenuate induction of intestinal epithelial proinflammatory gene expression and reduce the severity of dextran sodium sulfate-induced colitis. J Immunol 168:5260.

McSorley, S. J., B. D. Ehst, Y. Yu, and A. T. Gewirtz. 2002. Bacterial flagellin is an effective adjuvant for CD4+ T cells in vivo. J Immunol 169:3914.

McSorley, S. J., B. D. Ehst, Y. Yu, and A. T. Gewirtz. 2002. Bacterial flagellin is an effective adjuvant for CD4+ T cells in vivo. J Immunol 169:3914.

Reed, K. A., M. E. Hobert, C. E. Kolenda, K. A. Sands, M. Rathman, M. O'Connor, S. Lyons, A. T. Gewirtz, P. J. Sansonetti, and J. L. Madara. 2002. The Salmonella typhimurium flagellar basal body protein FliE is required for flagellin production and to induce a proinflammatory response in epithelial cells. J Biol Chem 277:13346.

Gewirtz, A. T., T. A. Navas, S. Lyons, P. J. Godowski, and J. L. Madara. 2001. Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J Immunol 167:1882.

Gewirtz, A. T., P. O. Simon, Jr., C. K. Schmitt, L. J. Taylor, C. H. Hagedorn, A. D. O'Brien, A. S. Neish, and J. L. Madara. 2001. Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. J Clin Invest 107:99.

Sitaraman, S. V., D. Merlin, L. Wang, M. Wong, A. T. Gewirtz, M. Si-Tahar, and J. L. Madara. 2001. Neutrophil-epithelial crosstalk at the intestinal lumenal surface mediated by reciprocal secretion of adenosine and IL-6. J Clin Invest 107:861.

Neish, A. S., A. T. Gewirtz, H. Zeng, A. N. Young, M. E. Hobert, V. Karmali, A. S. Rao, and J. L. Madara. 2000. Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination. Science 289:1560.

Gewirtz, A. T., A. S. Rao, P. O. Simon, Jr., D. Merlin, D. Carnes, J. L. Madara, and A. S. Neish. 2000. Salmonella typhimurium induces epithelial IL-8 expression via Ca(2+)-mediated activation of the NF-kappaB pathway. J Clin Invest 105:79.

Mazzucchelli, L., J. B. Burritt, A. J. Jesaitis, A. Nusrat, T. W. Liang, A. T. Gewirtz, F. J. Schnell, and C. A. Parkos. 1999. Cell-specific peptide binding by human neutrophils. Blood 93:1738.

Gewirtz, A. T., A. M. Siber, J. L. Madara, and B. A. McCormick. 1999. Orchestration of neutrophil movement by intestinal epithelial cells in response to Salmonella typhimurium can be uncoupled from bacterial internalization. Infect Immun 67:608.

Gewirtz, A. T., V. V. Fokin, N. A. Petasis, C. N. Serhan, and J. L. Madara. 1999. LXA4, aspirin-triggered 15-epi-LXA4, and their analogs selectively downregulate PMN azurophilic degranulation. Am J Physiol 276:C988.

Merlin, D., A. Steel, A. T. Gewirtz, M. Si-Tahar, M. A. Hediger, and J. L. Madara. 1998. hPepT1-mediated epithelial transport of bacteria-derived chemotactic peptides enhances neutrophil-epithelial interactions. J Clin Invest 102:2011.

Gronert, K., A. Gewirtz, J. L. Madara, and C. N. Serhan. 1998. Identification of a human enterocyte lipoxin A4 receptor that is regulated by interleukin (IL)-13 and interferon gamma and inhibits tumor necrosis factor alpha-induced IL-8 release. J Exp Med 187:1285.

Gewirtz, A. T., K. F. Seetoo, and E. R. Simons. 1998. Neutrophil degranulation and phospholipase D activation are enhanced if the Na+/H+ antiport is blocked. J Leukoc Biol 64:98.

Gewirtz, A. T., B. McCormick, A. S. Neish, N. A. Petasis, K. Gronert, C. N. Serhan, and J. L. Madara. 1998. Pathogen-induced chemokine secretion from model intestinal epithelium is inhibited by lipoxin A4 analogs. J Clin Invest 101:1860.

Gewirtz, A. T., and E. R. Simons. 1997. Phospholipase D mediates Fc gamma receptor activation of neutrophils and provides specificity between high-valency immune complexes and fMLP signaling pathways. J Leukoc Biol 61:522.

Seetoo, K. F., J. E. Schonhorn, A. T. Gewirtz, M. J. Zhou, M. E. McMenamin, L. Delva, and E. R. Simons. 1997. A cytosolic calcium transient is not necessary for degranulation or oxidative burst in immune complex-stimulated neutrophils. J Leukoc Biol 62:329.

Margolis, H. C., Y. P. Zhang, A. Gewirtz, J. Van Houte, and E. C. Moreno. 1993. Cariogenic potential of pooled plaque fluid from exposed root surfaces in humans. Arch Oral Biol 38:131.