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, PhD

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

https://pubmed.ncbi.nlm.nih.gov/?term=Chang+EB

Gut Microbe-Host Interactions and their Role in Health and Disease

Pierre JF, Hinterleitner R, Bouziat R, Hubert N, Leone V, Miyoshi J, Jabri B, Chang EB. Data on changes to mucosal inflammation and the intestinal microbiota following dietary micronutrients in genetically susceptible hosts. Data Brief. 2018 Aug 15;20:387-393.

Harris KG, Chang EB. The intestinal microbiota in the pathogenesis of inflammatory bowel diseases: new insights into complex disease. Clin Sci (Lond). 2018 Sep 18;132(18):2013-2028.

Zhong X, Frazier K, Weng X, Li Y, Cham CM, Dolan K, Zhu X, Hubert N, Tao Y, Lin F, Martinez-Guryn K, Huang Y, Wang T, Liu J, He C, Chang EB, Leone V. Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m6A mRNA Methylation. Cell Rep. 2018 Nov 13;25(7):1816-1828.

Wun K, Theriault BR, Pierre JF, Chen EB, Leone VA, Harris KG, Xiong L, Jiang Q, Spedale M, Eskandari OM, Chang EB, Ho KJ. Microbiota control acute arterial inflammation and neointimal hyperplasia development after arterial injury. PLoS One. 2018 Dec 6;13(12):e0208426.

Schwartz MH, Wang H, Pan JN, Clark WC, Cui S, Eckwahl MJ, Pan DW, Parisien M, Owens SM, Cheng BL, Martinez K, Xu J, Chang EB, Pan T, Eren AM. Microbiome characterization by high-throughput transfer RNA sequencing and modification analysis. Nat Commun. 2018 Dec 17;9(1):5353.

Regulation and Role of Epithelial Stress Proteins in Maintaining Intestinal Homeostasis

Wang Y, Lin F, Zhu X, Leone VA, Dalal SR, Tao Y, Messer JS, Chang EB. Distinct roles of intracellular heat shock protein 70 (Hsp70) in maintaining gastrointestinal homeostasis.  American Journal of Physiology Gastrointestinal and Liver Physiology. 2018 Feb 1;314(2):G164-G178.

Rentea RM, Guo Y, Zhu X, Musch MW, Chang EB, Gourlay DM, Liedel JL. Role of intestinal Hsp70 in barrier maintenance: contribution of milk to the induction of Hsp70.2.  Pediatr Surg Int. 2018 Mar;34(3):323-330.

Intestinal Epithelial Biology and Pathobiology

Uchiyama K, Sakiyama T, Hasebe T, Musch MW, Miyoshi H, Nakagawa Y, He TC, Lichtenstein L, Naito Y, Itoh Y, Yoshikawa T, Jabri B, Stappenbeck T, Chang EB. Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development. Scientific reports. 2016;6:32094.

Nobutani K, Miyoshi J, Musch MW, Nishiyama M, Watanabe J, Kaneko A, Yamamoto M, Yoshida M, Kono T, Jeong H, Chang EB. Daikenchuto (TU-100) alters murine hepatic and intestinal drug metabolizing enzymes in an in vivo dietary model: effects of gender and withdrawal.  Pharmacology Research & Perspectives. 2017 Oct;5(5).

Beck MW, Kathayat RS, Cham CM, Chang EB, Dickinson BC. Michael addition-based probes for ratiometric fluorescence imaging of protein S-depalmitoylases in live cells and tissues. Chem Sci. 2017 Nov 1;8(11):7588-7592.

Miyoshi J, Nobutani K, Musch MW, Ringus DL, Hubert NA, Yamamoto M, Kase Y, Nishiyama M, Chang EB. Time-, Sex-, and Dose-Dependent Alterations of the Gut Microbiota by Consumption of Dietary Daikenchuto (TU-100). Evid Based Complement Alternat Med. 2018 Feb 22;2018:7415975.

Pierre JF, Hinterleitner R, Bouziat R, Hubert NA, Leone V, Miyoshi J, Jabri B, Chang EB. Dietary antioxidant micronutrients alter mucosal inflammatory rist in murine model of genetic and microbial susceptibility. J Nutr Biochem. 2018 Apr;54:95-104.

Prevention and Basis of Colonic Carcinogenesis

Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Man Lei Y, Jabri B, Alegre ML, Chang EB, Gajewski TF. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015.

Tao Y, Messer JS, Goss KH, Hart J, Bissonnette M, Chang EB. Hsp70 exerts oncogenic activity in the Apc mutant Min mouse model. Carcinogenesis. 2016.

Hasebe T, Matsukawa J, Ringus D, Miyoshi J, Hart J, Kaneko A, Yamamoto M, Kono T, Fujiya M, Kohgo Y, Wang CZ, Yuan CS, Bissonnette M, Musch MW, Chang EB. Daikenchuto (TU-100) Suppresses Tumor Development in the Azoxymethane and APC<sup>min/+</sup> Mouse Models of Experimental Colon Cancer. Phytother Res. 2017 Jan;31(1):90-99.

Meisel M, Hinterleitner R, Pacis A, Chen L, Earley ZM, Mayassi T, Pierre JF, Ernest JD, Galipeau HJ, Thuille N, Bouziat R, Buscarlet M, Ringus DL, Wang Y, Li Y, Dinh V, Kim SM, McDonald BD, Zurenski MA, Musch MW, Furtado GC, Lira SA, Baier G, Chang EB, Eren AM, Weber CR, Busque L, Godley LA, Verdu EF, Barreiro LB, Jabri B. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature. 2018 May;557(7706):580-584.

BPHYS Student

Alon Shaiber, PhD