Andrew GewirtzFaculty Regents’ Professor and Distinguished University Professor Institute for Biomedical Sciences
Ph.D., Biochemistry, Boston University School of Medicine, Boston MA, 1996
Andrew Gewirtz, Regents’ Professor and Distinguished University Professor at Georgia State University, specializes in research on innate immunity, microbiome, intestinal inflammation and obesity/diabetes. Inflammation plays a central role in many disease states, and his goal is to understand the normal mechanisms by which pro-inflammatory signals protect against microbes and discern how they go awry in disease states. His primary area of focus is on the intestinal epithelium.
Gewirtz earned his Ph.D. in Biochemistry from Boston University School of Medicine.
Innate Immunity, Microbiome, Intestinal Inflammation and Obesity/Diabetes
It is becoming increasingly apparent that inflammation plays a central role in many disease states including “classic” inflammatory diseases such as inflammatory bowel disease to chronic disorders such as obesity, type-2 diabetes and cancer. Considering the physiological role of most pro-inflammatory processes seems geared to protect against microbes, our goal is to understand the normal mechanisms by which pro-inflammatory signals protect against microbes and discern how they go awry in disease states. Our primary area of focus is on the intestinal epithelium, which 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 the microbial and immunological communities in its midst. Specifically, the epithelia shapes the composition and locale of intestinal bacteria by producing antimicrobial substances and recruiting immune cells to efficiently clear bacteria that disturb equilibrium in the intestine. These pathways can go awry and result in chronic inflammation if the intestine “inherits” an aberrant microbial community and/or immune dysfunction.
- Carvalho FA, Koren O, Goodrich JK, Johansson ME, Nalbantoglu I, Aitken JD, Su Y, Chassaing B, Walters WA, González A, Clemente JC, Cullender TC, Barnich N, Darfeuille-Michaud A, Vijay-Kumar M, Knight R, Ley RE, Gewirtz AT. Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe. 2012 16;12(2):139-52.
- Carvalho FA, Nalbantoglu I, Ortega-Fernandez S, Aitken JD, Su Y, Koren O, Walters WA, Knight R, Ley RE, Vijay-Kumar M, Gewirtz AT. Interleukin-1β (IL-1β) promotes susceptibility of Toll-like receptor 5 (TLR5) deficient mice to colitis. Gut. 2012 Mar;61(3):373-84.
- Carvalho FA, Aitken JD, Vijay-Kumar M, Gewirtz AT. Toll-like receptor-gut microbiota interactions: perturb at your own risk! Annu Rev Physiol. 2012;74:177-98.
- Vijay-Kumar, M., J. D. Aitken, F. A. Carvalho, T. C. Cullender, S. Mwangi, S. Srinivasan, S. V. Sitaraman, R. Knight, R. E. Ley, and A. T. Gewirtz. 2010. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328:228-231.
- Frias, A.F. Vijay-Kumar, Gentsch, J.R. Crawford, Carvalho, S.E., Estes, M.K. and A. T. Gewirtz. 2010. Intestinal epithelia activate anti-viral signaling via intracellular sensing of rotavirus structural components. Mucos. Immunol. 3(6):622-32.
- Vijay-Kumar, M., F. A. Carvalho, J. D. Aitken, N. H. Fifadara, and A. T. Gewirtz. 2010. TLR5 or NLRC4 is necessary and sufficient for promotion of humoral immunity by flagellin. Eur J Immunol 40:3528-3534.
- Sanders, C. J., L. Franchi, F. Yarovinsky, S. Uematsu, S. Akira, G. Nunez, and A. T. Gewirtz. 2009. Induction of adaptive immunity by flagellin does not require robust activation of innate immunity. Eur J Immunol 39:359-371.
- Onyeagocha, C., M. S. Hossain, A. Kumar, R. M. Jones, J. Roback, and A. T. Gewirtz. 2009. Latent cytomegalovirus infection exacerbates experimental colitis. Am J Pathol 175:2034-2042.
- Vijay-Kumar, M., J. D. Aitken, C. J. Sanders, A. Frias, V. M. Sloane, J. Xu, A. S. Neish, M. Rojas, and A. T. Gewirtz. 2008. Flagellin treatment protects against chemicals, bacteria, viruses, and radiation. J Immunol 180:8280-8285.
- Sanders, C. J., D. A. Moore, 3rd, I. R. Williams, and A. T. Gewirtz. 2008. Both radioresistant and hemopoietic cells promote innate and adaptive immune responses to flagellin. J Immunol 180:7184-7192.
- Vijay-Kumar, M., C. J. Sanders, R. T. Taylor, A. Kumar, J. D. Aitken, S. V. Sitaraman, A. S. Neish, S. Uematsu, S. Akira, I. R. Williams, and A. T. Gewirtz. 2007. Deletion of TLR5 results in spontaneous colitis in mice. J Clin Invest 117:3909-3921.
- Yu, Y., S. Nagai, H. Wu, A. S. Neish, S. Koyasu, and A. T. Gewirtz. 2006. TLR5- mediated phosphoinositide 3-kinase activation negatively regulates flagellin-induced proinflammatory gene expression. J Immunol 176:6194-6201.
- Sanders, C. J., Y. Yu, D. A. Moore, 3rd, I. R. Williams, and A. T. Gewirtz. 2006. Humoral immune response to flagellin requires T cells and activation of innate immunity. J Immunol 177:2810-2818.
- Vijay-Kumar, M., J. R. Gentsch, W. J. Kaiser, N. Borregaard, M. K. Offermann, A. S. Neish, and A. T. Gewirtz. 2005. Protein kinase R mediates intestinal epithelial gene remodeling in response to double-stranded RNA and live rotavirus. J Immunol 174:6322-6331.
- Sitaraman, S. V., J. M. Klapproth, D. A. Moore, 3rd, C. Landers, S. Targan, I. R. Williams, and A. T. Gewirtz. 2005. Elevated flagellin-specific immunoglobulins in Crohn's disease. Am J Physiol Gastrointest Liver Physiol 288:G403-406.
- Yu, Y., H. Zeng, M. Vijay-Kumar, A. S. Neish, D. Merlin, S. V. Sitaraman, and A. T. Gewirtz. 2004. STAT signaling underlies difference between flagellin-induced and tumor necrosis factor-alpha-induced epithelial gene expression. J Biol Chem 279:35210-35218.
- Lyons, S., L. Wang, J. E. Casanova, S. V. Sitaraman, D. Merlin, and A. T. Gewirtz. 2004. Salmonella typhimurium transcytoses flagellin via an SPI2-mediated vesicular transport pathway. J Cell Sci 117:5771-5780.
- 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 189:1914-1920.
- 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:G282-290.
- 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 169:3914-3919.