Publications and Grant Funding

 

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

  • 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.

*Selected as Editors’ choice for 2012; featured in Nature Med 18;1186-7, 2012;Nature (News and Views) 487:47-8, 2012; Nature Rev (Gastro&Hepatology)157: 2012*

  • Stefka AT, Feehley T, Tripathi P, Qiu J, McCoy K, Mazmanian SK, Tjota MY, Seo GY, Cao S, Theriault BR, Antonopoulos DA, Zhou L, Chang EB, Fu YX, Nagler CR. Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13145-50
  • Leone VA, Gibbons, SM, Martinez K, Hutchison AL, Huang EY, Cham CM, Pierre JF, Heneghan AF, Nadimpalli A, Hubert N, Zale E, Wang Y, Theriault B, Dinner AR, Musch MW, Kudsk KA,. Prendergast BJ, Gilbert JA, and Chang EB. Effects of diurnal variation of gut microbes and high fat feeding on host circadian clock function and metabolism. 2015   Cell Host & Microbe, 2015;17(5):681-9.
  • Ma L, Kim J, Hatzenpichler R, Karymov MA, Hubert N, Hanan IM, Chang EB, Ismagilov RF. Genetically targeted microfluidic cultivation validated by isolation of a “Most Wanted” microbe from the human gut. Proc. Natl. Acad. Sci 2014. Jul 8;111(27):9768-73.
  • Bellaguarda E, Chang EB. IBD and the Gut Microbiota-from Bench to Personalized Medicine. Current gastroenterology reports. 2015;17(4):439.
  • Devkota S, Chang EB. Interactions between Diet, Bile Acid Metabolism, Gut Microbiota, and Inflammatory Bowel Diseases. Digestive diseases. 2015;33(3):351-6.
  • Sivan, A., Corrales, L., Hubert, N., Williams, J. B., Aquino-Michaels, K., Earley, Z. M., Benyamin, F.W., Lei,Y.M., Jabri, B., Alegre, M-L., Chang E.B., Gajewski, T. F. (2015). Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science 2015; 350(6264), 1084–1089.
  • Kamdar, K., Khakpour, S., Chen, J., Leone, V., Brulc, J., Mangatu, T., Antonopoulos, D.A., Chang E.B., Kahn, S.A., Kirschner, B.S., Young, G., DePaolo, R. W. Genetic and Metabolic Signals during Acute Enteric Bacterial Infection Alter the Microbiota and Drive Progression to Chronic Inflammatory Disease. Cell Host & Microbe 2016 19(1), 21–31.
  • Howe A, Ringus DL, Williams RJ, Choo ZN, Greenwald SM, Owens SM, Coleman ML, Meyer F, Chang EB. Divergent responses of viral and bacterial communities in the gut microbiome to dietary disturbances in mice. The ISME journal. 2016;10(5):1217-27
  • Minter MR, Zhang C, Leone V, Ringus DL, Zhang X, Oyler-Castrillo P, Musch MW, Liao F, Ward JF, Holtzman DM, Chang EB, Tanzi RE, Sisodia SS. Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease. Scientific reports. 2016;6:30028.
  • Vineis J., Ringus, D., Morrison, H., Delmont, T., Dalal, S., Raffals, L. Antonopoulos, D., Rubin, D., Eren, A.M., Chang, E. Sogin, M. Patient-Specific Bacteroides Genome Variants in Pouchitis. MBio 7, e01713-16- (2016).
  • Huang Y, Dalal S, Antonopoulos D, Hubert N, Raffals LH, Dolan K, Weber C, Messer JS, Jabri B, Bendelac A, Eren AM, Rubin DT, Sogin M, Chang EB. Early Transcriptomic Changes in the Ileal Pouch Provide Insight into the Molecular Pathogenesis of Pouchitis and Ulcerative Colitis. Inflamm Bowel Dis. 2017;23(3):366-78.
  • Minter MR, Hinterleitner R, Meisel M, Zhang C, Leone V, Zhang X, Oyler-Castrillo P, Zhang X, Musch MW, Shen X, Jabri B, Chang EB, Tanzi RE, Sisodia SS. Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APP<sub>SWE</sub>/PS1<sub>ΔE9</sub> murine model of Alzheimer’s disease. Sci Rep. 2017 Sep 5;7(1):10411.
  • Touw K, Ringus DL, Hubert N, Wang Y, Leone VA, Nadimpalli A, Theriault BR, Huang YE, Tune JD, Herring PB, Farrugia G, Kashyap PC, Antonopoulos DA, Chang EB. Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models. Physiol Rep. 2017 Mar;5(6).
  • Miyoshi J, Bobe AM, Miyoshi S, Huang Y, Hubert N, Delmont TO, Eren AM, Leone V, Chang EB. Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and Inflammatory Bowel Disease in Genetically Prone Offspring. Cell Rep. 2017 Jul 11;20(2):491-504.

Regulation and Role of Epithelial Stress Proteins in Maintaining Intestinal Homeostasis

  • 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.
  • Hu S, Zhu X, Triggs JR, Tao Y, Wang Y, Lichtenstein L, Bissonnette M, Musch MW, Chang EB. Inflammation-induced, 3’UTR-dependent translational inhibition of Hsp70 mRNA impairs intestinal homeostasis. Am J Physiol 296 (5) G1003-1011. 2009
  • Kang R, Zhang Q, Hou W, Yan Z, Chen R, Bonaroti J, Bansal P, Billiar TR, Tsung A, Wang Q, Bartlett DL, Whitcomb DC, Chang EB, Zhu X, Wang H, Lu B, Tracey KJ, Cao L, Fan XG, Lotze MT, Zeh HJ 3rd, and Tang D. Intracellular HMGB1 Inhibits Inflammatory Nucleosome Release and Limits Acute Pancreatitis in Mice. Gastroenterology 2014 Apr 146(4): 1097-2107
  • Zhu X, Messer JS, Wang Y, Lin F, Cham CM, Chang J, Billiar TR, Lotze MT, Boone DL, and Chang EB. HMGB1 Controls the Cellular Autophagy/Apoptosis Checkpoint During Inflammation.  J. Clin Invest 2015 Feb 2. pii: 76344.
  • Inaba Y, Ueno N, Numata M, Zhu X, Messer JS, Boone DL, Fujiya M, Kohgo Y, Musch MW, Chang EB. Soluble bioactive microbial mediators regulate proteasomal degradation and autophagy to protect against inflammation-induced stress. American journal of physiology Gastrointestinal and liver physiology. 2016
  • 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.  Am J Physiol Gastrointest Liver Physiol. 2017 Oct 19

Intestinal Epithelial Biology and Pathobiology

  • Field MJ, Rao MC and Chang EB. Intestinal electrolyte transport and diarrheal disease. N Engl J Med (2 part article) 321: 800-806, 879-883, 1989.
  • 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 & Microbe, 1(4): 299-309, 2007
  • Vavricka SR, Musch MW, Chang JE, Nakagawa Y, Phanvijhitsiri K, Waypa TS, Merlin D, Schneewind O, and Chang EB. hPepT1 transports muramyl dipeptide, activating NF-B and stimulating IL-8 secretion in human colonic Caco2/bbe cells. Gastroenterology 127: 1401-1409, 2004
  • Musch MW, Arvans, D, Walsh-Reitz M, Uchiyama K, Fukuda M and Chang EB. Synaptotagmin I binds intestinal epithelial NHE3 and mediates cAMP-and Ca2+-induced endocytosis by recruitment of AP2 and clathrin. Am J Physiol, 292(6):G1549-G1558, 2007
  • Lu L, Yu Y, Guo Y, Wang Y, Chang EB, Claud EC. Transcriptional modulation of intestinal innate defense/inflammation genes by preterm infant microbiota in a humanized gnotobiotic mouse model. PloS one. 2015;10(4)
  • Ward MA, Pierre JF, Leal RF, Huang Y, Shogan B, Dalal SR, Weber CR, Leone VA, Musch MW, An GC, Rao MC, Rubin DT, Raffals LE, Antonopoulos DA, Sogin ML, Hyman NH, Alverdy JC, Chang EB. Insights into the pathogenesis of ulcerative colitis from a murine model of stasis-induced dysbiosis, colonic metaplasia, and genetic susceptibility. American journal of physiology Gastrointestinal and liver physiology. 2016;310(11):G973-88.
  • Hasebe T, Ueno N, Musch MW, Nadimpalli A, Kaneko A, Kaifuchi N, Watanabe J, Yamamoto M, Kono T, Inaba Y, Fujiya M, Kohgo Y, Chang EB. Daikenchuto (TU-100) shapes gut microbiota architecture and increases the production of ginsenoside metabolite compound K. Pharmacology research & perspectives. 2016;4(1):e00215.
  • 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  Pharmacol Res Perspect. 2017 Oct;5(5)

Prevention and Basis of Colonic Carcinogenesis

  • Tao Y, Hart J, Lichtenstein, L, Joseph LJ, Ciancio MJ, Hu S, Chang EB, Bissonnette M. Inducible Heat Shock Protein 70 Prevents Multifocal Flat Dysplastic Lesions and Invasive Tumors in an Inflammatory Model of Colon Cancer. Carcinogenesis 30 (1); 175-182. 2009
  • Dennis KL, Wang Y, Blatner NR, Wang S, Saadalla A, Trudeau E, Roers A, Weaver CT, Lee JJ, Gilbert JA, Chang EB, and Khazaie K. Adenomatous polyps are driven by microbe-instigated focal inflammation and are controlled by IL-10-producing T cells. Cancer Res 73(19): 5905-5913, 2013
  • 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 *Equal contribution
  • 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, Han 18(1): 94-100. 2012.
  • Hu S, Liu L, Chang EB, Wang JY, Raufman JP. Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells. Molecular cancer. 2015;14(1):180.
  • 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.

See more publications at: http://www.ncbi.nlm.nih.gov/pubmed/?term=Chang+EB

Grant Funding

R01- Exploring Paneth Cell Peptide YY (PYY), a unique anti-microbial peptide that maintains fungal commensalism, in the pathogenesis of ileal Crohn’s Disease

R37 – Cytoprotective Role of Heat Shock Proteins in IBD (NIH MERIT Award)

P30 – (DDRCC)  IBD and Mucosal Inflammation, Immunology, and Micobiology of the G.I. tract.

T32  Research Training in Digestive Diseases and Nutrition

T35 Short Term Training: Health Professional Students

Kenneth Rainin Foundation- Experimental and Clinical Studies of a Novel Antimicrobial Peptide Regulator of Mycobiome Commensalism in Health and IBD

CCT Searle Funds: Role of Gut Microbiota in Determining Drug Efficacy and Toxicity