Dr. Aiping Zhao’s research area is in gut physiology, specifically immune regulation of gut function. Our hypothesis is that gastrointestinal tract contributes to host defense against various pathogens through the stereotypic functional responses that are orchestrated by the profile of cytokines (Th1 or Th2) produced by the host. Cytokines bind to the receptors linking to the activation of STAT signaling pathways, which then lead to the expression of gene clusters that orchestrate stereotypic effects on gut function.
We have demonstrated that upregulation of Th1 versus Th2 cytokines induced stereotypic and often opposing changes in smooth muscle and epithelial cell responses that are important for host resistance. We have also demonstrated that nematode infection provided an immunoregulatory-mediated protection against a murine model of IBD and improved gut function. Our current work is focusing on the downstream molecules of Th2 cytokine-activated Stat6 or Th1 cytokine-activated Stat4 signaling pathway that are involved in the regulation of gut function.
The long-term goal of our research is to identify the potential therapeutic targets for gastrointestinal disease such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) that are characterized by an immune balance.
- Zhao A, Wu ZQ, Pollack M, Rollwagen FM, Hirszel P, and Zhou X. Disulfiram Inhibits TNF-a-induced Cell Death. Cytokine, 2000; 12(9): 1356-1367.
- Zhao A, Bossone C, Piñeiro-Carrero V, and Shea-Donohue T. Colitis-induced Alterations in Adrenergic Control of Circular Smooth Muscle in Vitro in Rats. Journal of Pharmacology and Experimental Therapeutics 2001; 299(2): 768-774.
- Zhao A, McDermott J, Urban JF, Gause WC, Madden KB, Au Yeung C, Morris SB, Finkelman FD, and Shea-Donohue T. Dependence of IL4, IL-13 and Nematode –Induced Alterations in Murine Small Intestinal Smooth Muscle Contractility on Stat6 and Enteric Nerves. Journal of Immunology, 2003, 171: 948-954.
- Zhao A and Shea-Donohue T. Protease-Activated Receptor-2 Agonists Induce Contraction of Murine Small Intestine through Neurokinin Receptors. Am J Physiol Gastrointest Liver Physiol, 2003, 285: G696-G703.
- Zhao A, Morimoto A, Dawson H, Elfrey J, Madden KB, Gause WC, Min B, Finkelman FD, Urban JF, Shea-Donohue T. Immune regulation of protease-activated receptor-1 expression in murine small intestine during Nippostrongylus brasiliensis infection. Journal of Immunology, 2005, 175(4): 2563-2639.
- Morimoto M, Morimoto M, Zhao A, Madden KB, Dawson H, Finkelman FD, Mentink-Kane M, Urban JF, Wynn T, Shea-Donohue T. Functional importance of regional differences in localized gene expression of receptors for IL-13 in murine gut. Journal of Immunology, 2006, 176(1): 491-495.
- Zhao A, Urban JF Jr., Morimoto M, Elfrey JE, Madden KB, Finkelman FD, Shea-Donohue T. Up-regulation of 5-HT2A Receptor Contributes to Nematode Infection-Induced Hyper-contractility of Murine Intestinal Smooth Muscle. Gastroenterology, 2006, 131(2): 568-578.
- Li E, Zhao A, Shea-Donohue T, Singer SM. Mast cell-mediated changes in smooth muscle contractility during mouse giardiasis. Infection & Immunity, 2007, 75(9): 4514-4518.
- Scanlan BJ, Tuft B, Elfrey JE, Smith A, Zhao A, Morimoto M, Chmielinska JJ, Tejero-Taldo MI, Mak IuT, Weglicki WB, Shea-Donohue T. Intestinal inflammation caused by magnesium deficiency alters basal and oxidative stress-induced intestinal function. Mol Cell Biochem. 2007, 306(1-2):59-69.
- Shea-Donohue T, Thomas KE, Cody MJ, Zhao A, DeTolla LJ, Kopydlowski KM, Fukata M, Lira SA, and Vogel SN. Mice deficient in the CXCR2 ligand CXCL1 (KC/GRO-α) exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis. Innate Immunity, 2008, 14(2): 117-124.
- Zhao A, Urban JF, Anthony AM, Sun R, Stiltz J, van Rooijen N, Wynn T, Gause WC, and Shea-Donohue T. Th2 cytokine-Induced Alterations in Intestinal Smooth Muscle Function are Dependent on Alternatively Activated Macrophages. Gastroenterology, 2008, 135(1): 217-225.
- Sutton TL, Zhao A, Madden KB, Elfrey JE, Tuft BA, Sullivan CA, Urban, JF, and Shea-Donohue T. Anti-inflammatory Mechanisms of Enteric Heligmosomoides polygyrus Infection on TNBS-Induced Colitis in a Murine Model. Infection & Immunity, 2008, 76(10): 4772-82.
- Shea-Donohue T, Zhao A, Immune Regulation of Gut Function-The Role of T Helper 2 Cytokines and their Receptors. US Gastroenterology & Hepatology Review. 2008, 4(2):73-76.
- Morimoto M, Zhao A, Sun R, Stiltz J, Madden KB, Mentink-Kane M, Ramalingam T, Wynn TA, Urban JF Jr, Shea-Donohue T. IL-13 receptor alpha2 regulates the immune and functional response to Nippostrongylus brasiliensis infection. J Immunol. 2009, 83(3):1934-1939.
- Tripathi A, Lammers KM, Goldblum S, Shea-Donohue T, Netzel-Arnett S, Buzza MS, Antalis TM, Vogel SN, Zhao A, Yang S, Arrietta MC, Meddings JB, and Fasano A. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A. 2009, 106(39):16799-16804.
- Buzza MS, Netzel-Arnett S, Shea-Donohue T, Zhao A, Lin CY, List K, Szabo R, Fasano A, Bugge TH, and Antalis TM. Membrane-anchored serine protease matriptase regulates epithelial barrier formation and permeability in the intestine. Proc Natl Acad Sci U S A. 2010, 107(9): 4200-4205.
- Shea-Donohue T, Urban JF, Notari L, and Zhao A. Immune regulation of epithelial cell function: Implications for GI pathologies. International Dairy Journal. 2010, 20(4): 248-252.
- Shea-Donohue T, Fasano A, Smith A, and Zhao A. Enteric pathogens and gut function: role of cytokines and STATs. Gut Microboes, 2010, 1 (5): 316-324.
- Shea-Donohue T, Notari L, Stiltz J, Sun R, Madden KB, Urban JF, and Zhao A. Role of enteric nerves in the immune regulation of protease activated receptor-2 expression and function. Neurogastroenterology and Motility. 2010, 22(10): 1138-e291.
- Shea-Donohue T, Stiltz J, Zhao A, and Notari L. Mast Cells. Curr Gastroenterol Rep. 2010, 12(5): 349-357.
- Zhao A, Urban JF, Sun R, Stiltz J, Morimoto M, Notari L, Madden KB, Yang Z, Grinchuk V, Ramalingam TR, Wynn TA, and Shea-Donohue T. Critical role of IL-25 in nematode infection-induced alterations in intestinal function. J Immunol, 2010, 185(11): 6921-6929.
- Zhonghan Yang, Viktoriya Grinchuk, Siu Po Ip, Chun-Tao Che, Harry H. S. Fong, Lixing Lao, Justin C. Wu, Joseph J. Sung, Brian Berman, Terez Shea-Donohue, and Aiping Zhao. Anti-inflammatory activities of a Chinese herbal formula IBS-20 in vitro and in vivo. Evidence-Based Complementary and Alternative Medicine, 2012: 491496.
- Zhonghan Yang, Viktoriya Grinchuk, Joseph F. Urban Jr, Jennifer Bohl, Rex Sun, Luigi Notari, Shu Yan, Thirumalai Ramalingam, Achsah D. Keegan, Thomas A. Wynn, Terez Shea-Donohue, and Aiping Zhao. Novel Role of Macrophages as IL-25/IL-33-Responsive Cells in the Induction of Type 2 Immunity (submitted).
- Aiping Zhao, Zhonghan Yang, Rex Sun, Viktoriya Grinchuk, Ian E Anglin, Sarah Netzel-Arnett, Luigi Notari, Jennifer a Bohl, Kathleen B madden, Joseph F. Urban Jr, Toni M Antalis, and Terez Shea-Donohue. SerpinB2 is Indispensable to Th2 Immunity against Enteric Nematode Infection (submitted to J. Immunol.).
- Terez Shea-Donohue, Luigi Notari, Rex Sun, and Aiping Zhao. Mechanisms of smooth muscle responses to inflammation. Neurogastroenterology and Motility. 2012, 24 (9):802-811.
- Zhonghan Yang. Rex Sun, Viktoriya Grinchuk, Joan Antoni Fernandez Blanco, Luigi Notari, Jennifer A. Bohl, Leon P McLean, Thirumalai R. Ramalingam, Thomas A. Wynn, Joseph F. Urban Jr., Stefanie N. Vogel, Terez Shea-Donohue, and Aiping Zhao. IL-33-induced Alterations in Murine Intestinal Function and Cytokine Responses Are MyD88-, STAT6-, and IL-13-dependent. Am J Physiol Gastrointest Liver Physiol (in press).