Center for Global Health | Faculty

picture of Xuhang Li Xuhang Li

Assistant Professor of Medicine
Visiting Professorship, Shanghai Jiaotong University School of Medicine Renji Hospital

Academic Degrees

Ph.D., University of Maryland, College Park

School/Organization
School of Medicine

Department / Division
Department of Medicine
GI Division

Joint Departmental Affiliations
Johns Hopkins Center for Global Health

Center and Institute Affiliations
Center for Global Health

Departmental Address
Ross 746, 720 Rutland Ave, 720 Rutland Ave, Baltimore, MD 21205

Email: xuhang@jhmi.edu
Phone: 443-287-4804
Fax: 410-955-9677

For more information visit my personal web page.

Research and Professional Experience

Project I: Pathogenesis of Inflammatory Bowel Disease (IBD). IBD, consists of two subgroups, Crohn’s disease (CD) and ulcerative colitis (UC), are chronic and frequently disabling intestinal inflammatory disorders that affect more than a million Americans. It has a prevalence of ~ 0.2% of the Western population. In spite of intense researches, the pathogenesis of IBD is still elusive, and there is no cure for IBD. Several on-going projects include: 1). Biomarker discovery and development: Through various cutting-edge proteomic technologies (such as including protein chips/arrays, iTRAQ and 2D-DIGE) and multiplex sandwich ELISA, and using both human samples and mouse models, we have recently identified many interesting and high-value protein candidates that are potentially either involved in the pathogenesis of IBD or as IBD biomarkers. We are also identifying and developing serological biomarkers for irritable bowel syndrome (IBS). 2). Unraveling the mystery of opposite effects of smoking/nicotine on Crohn’s disease and ulcerative colitis. We are using multiple mouse IBD models and human IBD samples to understand the mysterious molecular mechanism of smoking/nicotine effects on IBD. 3). Understanding the molecular mechanisms of bacterial roles in IBD pathogenesis and parasite roles in IBD prevention. Current bacteria being studied in our lab include multiple commensal bacterial strains, including E. coli and B. fragilis. We are collaborating with Drs. Kathryn Chu and Gill Watermeyer in South Africa to understand the role of parasite worms (Ascaris lumbroides and Trichuris trichura adult worm) in preventing IBD. 4). Developing novel therapeutics for IBD and identify their molecular mechanisms. We are also in the process of developing multiple therapeutic reagents for clinical application of IBD therapy. The studies are being done at preclinical stages. Both in vitro cell models and in vivo mouse IBD models are being used in these studies.
Project #2: Molecular Mechanism in Membrane Trafficking/Regulation of Epithelial Na+/H+ exchanger 3 (NHE3). NHE3, one of the nine cloned human NHE isoforms, plays a key role in mammalian electrolyte balance through Na re-absorption. By proteomic approach, we recently identified a new NHE3-associated regulatory protein, casein kinase 2 (CK2) that is involved in the controlling NHE3 activity. We have lately also identified multiple single nucleotide polymorphisms (SNPs), some of which lead to alteration of both basal and regulated NHE3 activity. More interestingly, with collaboration with Drs. Donowitz and Brant, we found the SNPs are likely a major contributor to congenital diarrhea. The goal is to 1) identify the NHE3 C-terminus-associated regulatory components in NHE3 complexes and novel phosphorylation of NHE3 by pull-down/co-IP/mass spectrometry, and characterize their roles in the membrane trafficking and regulation of NHE3; and 2) identify additional potential human diseases associated with the newly identified NHE3 SNPs.

Keywords

inflammatory bowel disease (IBD), Crohns disease, ulcerative colitis, proteomics, irritable bowel syndrome (IBS), biomarkers, autoimmune liver diseases, NHE3, epithelial transport, diarrhea, drug resistance

Honors and Awards

2007-present: Visiting Research Professorship, Shanghai Jiaotong University School of Medicine, Renji Hospital
2005 The Scientist of the Year Award, GI Division, Johns Hopkins Department of Medicine
2002-2007 The NIH Research Scientist Career Development Award
1997 Graduate School Goldhaber Award, University of Maryland at College Park
1997 Elected to the Honor Society of PHI KAPPA PHI

Research Projects
The protective role of Helminth infection in inflammatory bowel disease in the Western Cape, South Africa
The incidence of inflammatory bowel disease (IBD) in the developing world is low compared to the developed world. One possible explanation is the "hygiene hypothesis" which suggests that overly sterile environments negatively impact immune development which predispose to immune mediated diseases...

Selected Publications

1. Alex, P., Ye, M., Sipes, J., Nguyen, T., Gonzales, L., Saksonov-Suhodrev, M., Zhang, T., Arora, Z., Centola, M., Guggino, S.E., Li, X. 2009. Clc-5 Knockout Mice Are More Susceptible to Dextran Sulphate Sodium Induced Colitis. Accepted to Journal of Immunology.
2. Conklin, L.S., Cuffari C., Zhang, T., Saatian, B., Brant, S.R., Okazaki, T., Alex, P., Miao, Y., Tse, M., Chen, T., Bayless, T.M., and Li, X. 2009. 6-MP Transport in Human Lymphocytes: Correlation with Drug-Induced Cytotoxicity. Accepted to Digestive Disease Science.
3. Chen, J., Sullivan, S., Anderson, T., Tan, A.C., Alex, J., Brant, S.R., Burek, L., Cuffari, C., Wang, H., Li, R., Conklin, L., Datta, L. W., Winslow, R., Zhu, H. and Li, X. 2009. Identification of novel serological biomarkers for inflammatory bowel disease using a protein chip of whole E. coli proteome. Molecular and Cellular Proteomics. (Epub ahead of print, April 7, www.mcponline.org/cgi/reprint/M900059-MCP200v1)
4. Zachos N.C., Li, X., Kovbasnjuk, O., Hogema, B., Sarker, R., Li, M., de Jonge, H., Donowitz, M. 2009. NHERF3 (PDZK1) reconstitutes elevated intracellular calcium ([Ca2+]i) inhibition of NHE3 activity by a mechanism different from NHERF2. J. Biol. Chem. (accepted; in press).
5. Zachos, N.C., van Rossum, D.B., Li, X., Caraveo, G., Sarker, R., Cha, B., Mohan, S., Desiderio, S., Patterson, R.L., Donowitz, M. 2009. Phospholipase C-? binds directly to the Na+/H+ exchanger 3 and is required for calcium regulation of exchange activity. J. Biol. Chem. (In press).
6. Sullivan, S., Alex P., Dassopoulos, T., Zachos, N.C., Iacobuzio-Donahue, C., Donowitz, M., Brant, S.R., Cuffari, C., Harris, M.L., Datta L.W., Conklin, L., Chen, C., and Li, X. 2009. Down-Regulation of Sodium Transporters and NHERF Proteins in IBD Patients and Mouse Colitis Models: Potential Contributors to IBD-associated Diarrhea. Inflammatory Bowel Disease. 15(2), 261-274.
7. Donowitz, M., Mohan, S., Chen T,E., Lin R., Cha, B., Zachos, NC., Murtazina R., and Sarker R., and Li, X. 2009. NHE3 regulatory Complexes . J. Exp. Biol. 212, 1638-46.
8. Alex, P, Zacho, N., Nguyen, T., Gonzales, L., Chen, T.E., Conklin, L.S., Centola, M, and Li, X. 2009. Distinct cytokine patterns identified from multiplex profiles of experimental colitis. Inflammatory Bowel Disease. 15(3), 341-352.
9. Alex, P., Gucek, M., Li, X. 2009. Applications of Proteomics in Study of Inflammatory Bowel Diseases: Current Status and Future Potential with Available Technologies. Inflammatory Bowel Disease. 15(4), 616-629.
10. Xu, J., Yang, C.-H., Chen, X.-Y., Li, X., Dai, M., Xiao, S.-D. 2008. A subset of ulcerative colitis with positive proteinase-3 antineutrophil cytoplasmic antibody. W. J. Gastroenterol. 14(45): 7012-5.
11. Zachos, N.C., Hodson, C., Kovbasnjuk, O., Li, X., Thelin, W.R., Cha, B., Milgram, S., Donowitz, M. 2008. Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism. Cell. Physiol. Biochem. 22, 693-740.
12. Li, X., Conklin, L., and Alex, P. 2008. New Serological Biomarkers of Inflammatory Bowel Diseases. World Journal of Gastroenterology. 14 (33), 5115-5124.
13. Sarker, R., Grønborg, M., Cha, B., Chen, Y., Mohan, S., Pandey, A., Litchfield, D., Donowitz, M. and Li, X. 2008. CK2 Binds to the C-Terminus of NHE3 and Stimulates NHE3 Basal Activity by Phosphorylating a Separate Site. Mol. Biol. Cell. 19(9), 3859-3870.
14. Li, X. and Donowitz, M. 2008. Fractionation of Subcellular Membrane Vesicles of Epithelial and Non-Epithelial cells by OptiPrepTM Density Gradient Ultracentrifugation. Methods in Molecular Biology/Molecular Medicine. 440:97-110.
15. Donowitz, M., Singh, S., Salahuddin, F. F., Hogema, B. M., Gucek, M., Cole, R. N., Chen, Y., Zachos, N., Kovbasnjuk, O., Lapierre, L., Broere, N., Goldenring, J., deJonge, H. Li, X. 2007. Proteome of the Murine Jejunal Brush Border. Journal of Proteome Research. 6 (10), 4068-4079.
16. Murtazina, R., Kovbasnjuk, O., Zachos, N., X. Li, Chen, Y., Hubbard, A., Hogema, B.M., Steplock D., Seidler, U., Hoque, K M., Tse, M., De Jonge, H.R., Weinman, E.J., and Donowitz, M. 2007. Tissue-specific regulation of sodium/proton exchanger isoform 3 activity in Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) null mice. cAMP inhibition is differentially dependent on NHERF1 and exchange protein directly activated by cAMP in ileum versus proximal tubule. J. Biol. Chem. 282(34):25141-51.
17. Donowitz, M and Li, X. 2007. Regulatory binding partner and complexes of NHE3. Physiological Review. 87 (3), 825-72.
18. Murtazina, R., Kovbasnjuk, O., Donowitz, M., and Li, X. 2006. Na+/H+ exchanger 3 activity and trafficking are lipid raft dependent. J. Biol. Chem. 281, 17845-17855.
19. Donowitz, M., Cha B., Zachos, N.C., Brett, C.L., Sharma, A., Tse, C.M., Li, X. 2005. NHERF Family and NHE3 Regulation. J. Physiol. (London). 567, 3-11.
20. Li, X., Zhang, H., Cheong, A., Leu, S., Chen, Y., Elowsky, C.G. and Donowitz M. 2004. Carbachol Regulation of Rabbit Ileal Brush Border NHE3 Occurs through Changes in NHE3 Trafficking and Complex Formation and is Src Dependent. J. Physiol (London). 556, 791-804.
21. Li, X., Leu, S., Birnbaum, M. J., Baibakov, B., Zhang, H., Shih, C. and Donowitz, M. 2004. Akt, PI-3 Kinase and PTEN are in lipid rafts in brush border of intestinal epithelial cells: potential involvement of Akt2 in stimulated Na absorption and differentiation. Gastroenterology. 126, 122-35.
22. Donowitz, M., Li, X. and Kim, J.H. 2003. Large multiprotein complexes are involved in short-term regulation of the epithelial brush border Na+/H+ exchanger NHE3. Physiol. News. 51, 20-21.
23. Akhter, S., Kovbasnjuk, O., Li, X., Cavet, M., Noel, J., Arpin, M., Hubbard, A.L. and Donowitz, M. 2002. Na+/H+ Exchanger 3 is in large centrally localized complexes on the brush border of proximal tubule-derived OK cells. Am. J. Physiol. Cell Physiol. 238, C927-940.
24. Li, X., Galli T., Leu, S., Louvard, D., and Donowitz, M. 2001. Na+/H+-exchanger 3 is present in the lipid rafts in the rabbit ileal brush border: A role for rafts in the trafficking of NHE3. J. Physiol. 537, 537-552.

Last Updated: 8/23/2009 | Update Your Faculty Page