The Faculty

Focus

Host-microbial interactions of the intestine signals/pathways that are involved in maintaining intestinal homeostasis

Education

M.D., The University of Chicago

B.A., Johns Hopkins University

Board Certifications

Internal Medicine
Gastroenterology

Medical School

University of Chicago Pritzker School of Medicine

Internship, Residency, and Fellowship

The University of Chicago Medicine

Memberships

American Gastroenterological Association
American Society of Clinical Investigation
Association of American Physicians
Federation of American Societies for Experimental Biology
Gastroenterology Research Group

BPHYS Students

Alon Shaiber

Clinical Interests

Research Summary

We have two major research interests:

1. The focus of our group is on the study of the intestinal microbes, particularly how they interact with the host. This relationship is fundamental to our health and, when perturbed, the consequences can be catastrophic.  In this regard, the emergence of “new age” disorders like diabetes, obesity, metabolic syndrome, cancer and autoimmune disorders over the past century may be related to large shifts in the composite human microbiome caused by changes in the environment and life styles. In genetically susceptible individuals, these factors can potentially trigger events that disturb immune and metabolic homeostasis, initiating the development of disease. Our efforts are therefore directed towards gaining a better understanding of what factors are involved in the selection and assembly of intestinal microbes, and how they can be used to reshape the enteric microbiome to prevent and treat disease. We employ cutting edge approaches that include cultivation-dependent and –independent technologies for microbial analysis, genetically modified and gnotobiotic mouse models, metabolic and functional measurements, and advanced bioinformatic tools to investigate both host and microbiome.

2. The role of heat shock protein in maintaining intestinal and immune homeostasis Heat shock proteins (HSPs) are a highly conserved family of multifunctional molecules. They play a role in mucosal cytoprotection, host-microbe interactions, innate immunity, cancer initiation and development, and in autophagy. Although many types are constitutively expressed, some, such as HSP70 and HSP25, are rapidly induced and preferentially synthesized under conditions of cellular stress and injury. Their physiological expression in the gut is maintained by cues and signals provided by the enteric microbiota.  In epithelial cells, their induction protects against toxic, oxidant, and thermal injury. Our laboratory, therefore, is investigating cellular and molecular mechanisms that mediate their cytoprotective effects in the context of mucosal inflammation. These studies involve correlations of molecular and biochemical techniques with physiological findings and imaging analysis.

Selected Papers

1.   Ren H, Musch MW, Kojima K, Boone D, Ma A, Chang EB.  Short-chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cells. Gastroenterology 121: 631-639 2001

2.  Kojima K, Musch MW, Ren H, Boone DL, Hendrickson BA, Ma A, Chang EB.  Enteric flora and lymphocyte derived cytokines determine expression of Hsp in mouse colonic epithelial cells.  Gastroenterology 124:1395-1407, 2003

3.  Petrof EO,  Kojima K, Ropeleski MJ, Musch MW, Tao Y, De Simone C, Chang EB. Probiotics inhibit NF-kB and induce heat shock proteins in colonic epithelial cells through proteasome inhibition. Gastroenterology 127: 474-1487, 2004

4.  Wu L, Estrada O, Zaborina O, Bains M, Le S, Kohler JE, Patel N,  Musch MW, Chang EB, Fu Y, Jacobs MA, Nishimura MI, Hancock REW,  Turner JR, Alverdy JC.  Recognition of host immune activation by Pseudomonas aeruginosa.  Science 309: 774-777, 2005

5.  Fujiya M, Musch MW, Nakagawa Y, Hu S, Alverdy J, Kohgo Y, Schneewind O, Jabri B, Chang EB. The Bacillus subtilis quorum-sensing molecule CSF contributes to  intestinal homeostasis via OCTN2, a host cell membrane transporter. Cell Host and Microbe,  1(4) 299-308, 2007

6.   Wang Y,  Hoenig, JD,  Malin KJ, Qamar S, Petrof EO, Sun J, Antonopoulos DA, Chang EB, Claud EC. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis.   ISMEJ  2009,  8: 944-954  PMCID 2713796.

7. Wang Y, Antonopoulos DA, Zhu X,  Harrell L, Hanan I, Alverdy JC, Meyer F, Musch MW, Young VB, Chang EB. Laser Capture Microdissection and Metagenomic Analysis of Intact Mucosa-associated Microbial Communities of Human Colon.  Appl Microbiol Biotechnol  2010 epub PMID: 20931185


8. Wang Y, Devkota S, Musch MW, Jabri B, Nagler C, Antonopoulos DA, Chervonsky A, Chang EB.  Regional mucosa-associated microbiota determine physiological expression of TLR2 and TLR4 in murine colon.  PLOS One   2010 5: e13607 PMCID:  2962643

9. Hu S, Wang Y, Lichtenstein L, Tao Y, Musch MW, Jabri B, Antonopoulos D, Claud EC, Chang EB.  Regional differences in colonic mucosa-associated microbiota determine the physiological expression of host heat shock proteins. Am. J. Physiol, 299(6) G1266-1275 2010 PMCID: 300624

10. Hu S*, Dong TS*, Dalal SR, Wu F, Bissonnette M, Kwon JH, and Chang EB.   The microbe-derived  short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer.   PlosOne,  6(1): 316221, 2011   PMCID 3024403

11.  Pekow J, Dougherty U, Mustafi R, Zhu H, Kocherginsky M, Rubin D, Hanauer S, Hart J, Chang EB, Fichera A, Joseph L, Bissonnette M.  miR-143 and miR-145 are down-regulated in ulcerative colitis: putative regulators of inflammation and protooncogenes.  Inflamm Bowel Dis,   epub May 6, doi: 10.1002/ibd21742 2011.  PMID:  21557394 PMCID in process

12.  Harrell L, Wang Y, Antonopoulos D, Young V, Lichtenstein L, Huang Y, Hanauer S, Chang E.  Standard colonic lavage alters the natural state of mucosal-associated microbiota in the human colon.  PlosOne, 7(2) e32545, 2012 PMCID:  3289660

13.   Devkota S, Wang Y,  Musch M, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA,  Jabri B, and Chang EB. Dietary fat-induced taurocholic acid production promotes pathobiont and colitis in IL 10-/-mice. Nature  487(7405) 104-108 .  2012. PMCID 3393783 (selected by Nature as 2013 Editors’ choice)

14.  Hansen JJ, Huang Y, Peterson DA, Goeser L, Fan TJ, Chang EB, and  Sartor RB. The Colitis-Associated transcriptional Profile of Commensal Bacteroides thetaiotaomicron Enhances Adaptive Immune Responses to a Bacterial Antigen. PLoS  One. 2012;7(8):e42645.PMCID: 3411805.

15.   Upadhyay V, Poroyko V, Kim TJ, Devkota S, Fu S, Liu D, Tumanov AV, Koroleva EP, Deng L, Nagler C, Chang EB, Tang H, Fu YX. Lymphotoxin regulates commensal responses to enable diet-induced obesity. Nat Immunol. 2012 Oct;13(10):947-53.  PMID: 22922363. PMCID in process