Andrew Scott Neish, MD

Epithelial Pathobiology
Immunology
Microbial Pathogenesis

Professor
Pathology & Laboratory Medicine

Pathology Division(s):
Anatomic Pathology
Experimental Pathology

Email Address:
aneish@emory.edu

Education:

B.A.   Wake Forest University, Winston-Salem, NC, - 1983

M.D.   University of North Carolina School of Medicine, Chapel Hill, NC, - 1988

Research Interests:

- Host-microbe interactions
Our laboratory studies innate and mucosal immunity relevant to infectious (Gram negative enterocolitis), idiopathic (idiopathic inflammatory bowel disease) and developmental (necrotizing enterocolitis) inflammatory disorders of the intestine. Specifically, our research program investigates the interactions of bacterial pathogens such as Salmonella, and their products with epithelial cells in an effort to understand the molecular mechanisms of pathological and commensal eukaryotic-prokaryotic relationships. Eukaryotic cells recognize bacteria via surface receptors (Toll-like receptors) that bind conserved microbial structural motifs (PAMPS). These PAMPS include the surface protein flagellin, which we have shown stimulates potent inflammatory responses in epithelia in vitro and in vivo. We are interested in the role flagellin plays in the pathogenesis of infectious enteritis, and potentially the role this prokaryotic protein plays in normal intestinal homeostasis. Bacteria are also thought to mediate interactions with eukaryotic cells by preformed effector proteins that are translocated into the host epithelia and usurp normal cellular functions. We are investigating a family of secreted prokaryotic effector proteins that we have shown have profound effects on host cellular signaling functions. The effects clearly involve immune surveillance, and may also influence cellular survival, proliferation and development. These proteins are cysteine proteases, which based on sequence homology with eukaryotic and viral proteases, act as deubiquitinating enzymes. We are also interested in effects of bacterially produced small molecules that can blunt inflammatory and survival responses by inhibition of native eukaryotic ubiquitin ligases. The laboratory employs a variety of microbiologic, genetic, biochemical and cell biological techniques to approach theses questions, including use of mammalian cell culture, murine and Drosophila models and large-scale expression profiling using microarray technology.

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Dr. Neish's research focuses on the interactions of bacteria with human epithelial cells in an effort to understand the molecular mechanisms of immune and inflammatory reactions that may mediate pathogenic and commensal relationships.

Honors / Awards:

Symposium Chair, Regulation of Epithelial Barrier and Host-Microbial Cross-talk, FASEB, 2005

Burroughs Wellcome Investigator in Pathogenesis of Infectious Disease, 2004-2009

Session Moderator, AGA, 2004

Dean's Clinical Investigator Award, Emory University, 2001-2006

Albert E. Levy Science Research Award, Emory University,, 2001

Bugher Foundation Fellow, Program in Molecular Biology of the Cardiovascular System, 1993-1994

Merit Award for Academic Achievement, University of North Carolina School of Medicine, Chapel Hill, NC, 1984-1986

Cum Laude, Wake Forest University, Winston-Salem, NC, 1983

Beta Beta Beta, Wake Forest University, Winston-Salem, NC, 1982

Selected Publications:

Published and Accepted Research Articles -

Zeng H, Wu H, Jones R, Yu Y, Lin P, Gewirtz AT, Neish AS. Flagellin/TLR5 responses in epithelia reveal intertwined activation of inflammatory and apoptotic pathways. Am. J. Physiol. 2006; 290: G96-G108.

Yu Y, Nagai S, Wu H, Neish AS, Koyasu S, Gewirtz AT.TLR5-mediated PI3K activation negatively regulates flagellin-induced pro-inflammatory gene expression. J. Immunol. 2006; 176:6194-201.

Ghartey-Tagoe EB, Babbin BA, Nusrat A, Neish AS, Prausnitz MR. Plasmid DNA and siRNA transfection of intestinal epithelial monolayers by electroporation. Int. J. Pharmaceutics. 2006; 315:122-133.

Franco AT, Israel DA, Washington MK, Fox JG, Rogers AB, Neish AS, Collier-Hyams L, Guillermo Perez-Perez GI, Hatakeyama M, Whitehead R, Krishna U, Ferrero RL, Gaus K, O'Brien DP, Peek RM. Activation of ¿-catenin by carcinogenic Helicobacter pylori. Proc. Natl. Acad. Sci. 2005;102:10646-10651.

Ghartey-Tagoe EB, Morgan JS, Neish AS, Prausnitz MR. Increased permeability of intestinal epithelial monolayers mediated by electroporation. J. Control Release 2005;103:177-190.

Collier-Hyams LS, Batten B, Sloane V, Neish AS. Bacterial modulation of epithelial signaling via deneddylation of Cul-1. J. Immunol (Cutting edge). 2005; 175:4194-4198.

Vijay-Kumar M, Gentsch JR, Kaiser WJ, Borregaard H, Offerman MK, Neish AS, Gewirtz AT. Protein kinase R mediates intestinal epithelial gene remodeling in response to double stranded RNA and live rotavirus. J. Immunol 2005; 174: 6322-6331.

Yu Y, Zeng H, Vijay-Kumar M, Neish AS, Merlin D, Sitaraman SV, Gewirtz AT. STAT signaling underlies difference between flagellin-induced and TNF alpha -induced epithelial gene expression. J Biol Chem. 2004; 279:35210-35218.

Pozharskaya VP, Weakland LL, Zimring JC, Krug LT, Unger ER, Neish A, Joshi H, Inoue N, Offermann MK. Short duration of elevated vIRF-1 expression during lytic replication of human herpesvirus 8 limits its ability to block antiviral responses induced by alpha interferon in BCBL-1 cells. J. Virol. 2004;78:6621-6635.

Ghartey-Tagoe EB, Morgan JS, Ahmed K, Neish AS, Prausnitz MR. Electroporation-mediated delivery of molecules to model intestinal epithelia. Int. J. Pharmeceutics, 2004; 270:127-138.

Sun J, Hobert ME, Rao AS, Neish AS, Madara JL. Bacterial activation of beta-catenin signaling in human epithelia. Am J Physiol Gastrointest Liver Physiol. 2004

Lin PW, Simon PO, Gewirtz AT, Selsted ME, Neish AS, Ouellette AJ, Madara JL, Lencer WI. Paneth cell cryptdins act in vitro as apical paracrine regulators of the innate inflammatory response. J. Biol.Chem. 2004; 297:19902-19907.

Young AN, De Oliveira Salles PG, Lim SD, Cohen C, Petros JA, Marshall FF, Neish AS, Amin MB. Beta defensin-1, parvalbumin, and vimentin: a panel of diagnostic immunohistochemical markers for renal tumors derived from gene expression profiling studies using cDNA microarrays. Am. J. Surg. Pathol. 2003; 27:199-205.

Yu Y, Zeng H, Lyons S, Carlson A, Merlin D, Neish AS, Gewirtz AT. TLR5-mediated activation of p38 MAPK regulates epithelial IL-8 expression via a post-transcriptional mechanism. Am. J. Physiol. Gastrointest. Liver Physiol. 2003; 285:G282-G290.

Zeng H, Carlson AQ, Guo Y, Yu Y, Collier-Hyams L, Madara JL, Gewirtz AT, Neish AS, Flagellin is the major proinflammatory determinants of enteropathogenic Salmonella. J. Immunol. 2003; 171:3668-3574.

Gewirtz AT, Collier-Hyams LS, Young AN, Kucharzik T, Guilford W, Parkinson J, Williams IR, Neish AS, Madara JL. Lipoxin A4 analogs attenuate induction of intestinal epithelial pro-inflammatory gene expression and reduce the severity of DSS-induced colitis. J. Immunol. 2002; 168: 5260-5267.

Gewirtz AT, Collier-Hyams LS, Young AN, Kucharzik T, Guilford W, Parkinson J, Williams IR, Neish AS, Madara JL. Lipoxin A4 analogs attenuate induction of intestinal epithelial pro-inflammatory gene expression and reduce the severity of DSS-induced colitis. J. Immunol. 2002; 168: 5260-5267.

Collier-Hyams LS, Zeng H, Sun J, Tomlinson AD, Bao ZQ, Chen H, Madara JL, Orth K, Neish AS. Salmonella AvrA effector inhibits the key proinflammatory, anti-apoptotic NF-kB pathway. J. Immunol (Cutting edge). 2002; 169: 2846-2850.

Hunter S, Young A, Olson J, Brat DJ, Bowers G, Wilcox JN, Jaye D, Mendrinos S, Neish AS. Differential expression between pilocytic and anaplastic astrocytomas: identification of apolipoprotein D as a marker for low-grade, non-infiltrating primary CNS neoplasms. J. Neuropathol. Exp. Neurol. 2002; 61:275-281.

DeCaterina R, Bourcier T, Laufs U, LaFata V, Lazzerini G, Neish AS, Libby P, Liao JK. Induction of endothelial-leukocyte interaction by interferon gamma requires coactivation of nuclear factor-kB, Arterioscler. Thromb Vasc. Biol 2001; 21:227-232.

Lee YW, K¿hn H, Hennig B, Neish AS, Toborek M. IL-4-induced oxidative stress upregulatesVCAM-1 gene expression in human endothelial cells. J Mol Cell Cardiol, 2001; 33:83-94.

Evans C-O, Young AN, Brown MR, Brat DJ, Parks JS, Neish AS, Oyesiku NM. Novel patterns of gene expression in pituitary adenomas identified by complementary deoxyribonucleic acid microarray analysis and quantitative reverse transcription-polymerase chain reaction. J. Clin. Endo. Metab. 2001; 86:3097-3107.

Young AN, Lim S, Cohen C, Marshall F, Petros J, Amin M, Neish AS. Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers. Am. J. Path. 2001; 158:1639-1651.

Gewirtz AT, Simon PO, Schmitt CK, O'Brian A, Neish AS, Madara JL. S. typhimurium translocates flagellin across model intestinal epithelia where it acts as an essential pro-inflammatory factor. J. Clin. Invest. 2001; 107:99-109.

Gewirtz A, Rao A, Simon PO, Merlin D, Carnes D, Madara JL, Neish AS. S. typhimurium induces epithelial IL-8 expression via Ca mediated activation of the NF-kB pathway, J. Clin. Invest. 2000; 105: 79-92.

Neish AS, Gewirtz AT, Zeng H, Young AN, Hobert M, Karmali V, Rao AS, Madara JL. Prokaryotic regulation of epithelial responses by inhibition of IkB-a ubiquitination, Science. 2000; 289, 1560-1563.

Gewirtz A, McCormick B, Petasis NA, Gronert K, Neish AS, Serhan CN, Madara JL. Pathogen-induced chemokine secretion from model intestinal epithelium is inhibited by lipoxin A4 analogs, J. Clin. Invest. 1998; 101:1860-1869.

Neish AS, Anderson SF, Parvin JD. Factors associated with the mammalian RNA polymerase II holoenzyme. Nuc. Acids Res. 1998; 26: 847-853.

Gerritsen ME, Williams A, Neish AS, Moore S, Shi Y, Collins T. CBP/p300 are transcriptional coactivators of p65. Proc. Natl. Acad. Sci. USA.

Read MA, Neish AS, Gerritsen ME, Collins T. Nuclear IkB-a and the post-induction transcriptional repression of E-selectin and VCAM1. J. Immunol.

Neish AS, Read MA, Thanos D, Pine R, Maniatis T, Collins T. Endothelial IRF-1 cooperates with NF-kB as a transcriptional activator of vascular cell adhesion molecule-1. Mol. Cell. Biol.

Read MA, Neish AS, Luscinskas FW, Palombella VJ, Maniatis T, Collins T. The proteasome pathway is required for cytokine-induced endothelial leukocyte adhesion molecule expression.

Neish AS, Khachigian LM, Park A, Baichwal VR, Collins T. Sp1 is a component of the cytokine-inducible enhancer in the promoter of vascular cell adhesion molecule-1. J. Biol. Chem.

Shu HB, Agranoff AB, Nabel EG, Leung K, Duckett CS, Neish AS, Collins T, Nabel GU. Differential regulation of VCAM-1 gene expression by specific NF-kB subunits in endothelial and epithelial cells

Neish AS, Loh E, Schoen F. Myocardial changes in cardiac transplant-associated coronary arteriosclerosis: Potential for timely diagnosis

Neish AS, Williams AJ, Palmer HJ, Whitley MZ, Collins T. Functional analysis of the human vascular cell adhesion molecule-1 promote

Ridker P, Chertow G, Karlson G, Neish AS, Schoen F. Bioprosthetic tricuspid valve stenosis associated with extensive plaque deposition in carcinoid heart disease. Am. Heart J

Book Chapters -

Neish AS. Flagellin mediated inflammation and anti-apoptosis, Themes review. Am. J. Physiol. In press

Collier-Hyams LS and Neish AS. Immune Relationship between Commensal Flora and the Mammalian Host. Cell Mol Life Sci. 2005; 62: 1339-1348.

Neish, AS. Cell Signaling pathways as targets for bacterial evasion and immunity. In: McFall-Ngai M, Henderson B, and Ruby E. eds. The influence of bacterial communities on host biology, 2005, Cambridge University Press, 375-398.

Neish, AS. Molecular aspects of intestinal epithelial cell-bacterial interactions that determine the development of intestinal inflammation. Inflamm. Bowel. Dis. 2004; 10:159-168.

Neish, AS. Bacterial inhibition of eukaryotic pro-inflammatory pathways. Immunologic Res. 2004; 29: 175-185.

Neish, AS. Microbial interference with host inflammatory responses. In: Hecht G, ed. Microbial Pathogens and the Intestinal Epithelial Cell. 2003 ASM press, Washington DC.175-190.

Neish AS. The gut microflora and intestinal epithelial cells: A continuing dialog. Microbes and Infection, 2002; 4: 309-317.

Other Publications -

Vijay-Kumar M, Wu H, Jones R, Grant G, Babbin B, King TP, Kelly D, Gewirtz AT, Neish AS. Flagellin suppresses epithelial apoptosis and limits disease during enteric infection. Am. J. Path. In press.