Thaddeus  Stappenbeck,  MD, PhD

Thaddeus Stappenbeck, MD, PhD


Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 444-3082


My lab is interested in discovering host and environmental factors that impact inflammation and wound repair at mucosal surfaces. These processes impact the pathogenesis of a number of disease states including inflammatory bowel disease. We use combinations of studies using human cells and tissues as well as mouse and in vitro models to approach these problems. The focal point of these studies is often the intestinal epithelial barrier. To make advances in this area, we have developed novel methods to model these cells under a variety of relevant conditions. We then study mechanisms by which the diet/microbiome as well as select stromal/immune cells impact this system. Our overarching goal is to understand combinations of genetic and environmental factors that affect specific epithelial cell function and thus predispose individuals to develop active intestinal inflammation.

View Publications on PubMed

Selected Publications:


Long-Term Culture Captures Injury-Repair Cycles of Colonic Stem Cells.

Wang Y, Chiang IL, Ohara TE, Fujii S, Cheng J, Muegge BD, Ver Heul A, Han ND, Lu Q, Xiong S, Chen F, Lai CW, Janova H, Wu R, Whitehurst CE, VanDussen KL, Liu TC, Gordon JI, Sibley LD, Stappenbeck TS.

Cell. 2019 Nov 14;179(5):1144-1159.e15. doi: 10.1016/j.cell.2019.10.015. Epub 2019 Nov 7.


PAI-1 augments mucosal damage in colitis.

Kaiko GE, Chen F, Lai CW, Chiang IL, Perrigoue J, Stojmirović A, Li K, Muegge BD, Jain U, VanDussen KL, Goggins BJ, Keely S, Weaver J, Foster PS, Lawrence DA, Liu TC, Stappenbeck TS.

Sci Transl Med. 2019 Mar 6;11(482). pii: eaat0852. doi: 10.1126/scitranslmed.aat0852.


Diet modulates colonic T cell responses by regulating the expression of a Bacteroides thetaiotaomicron antigen.

Wegorzewska MM, Glowacki RWP, Hsieh SA, Donermeyer DL, Hickey CA, Horvath SC, Martens EC, Stappenbeck TS, Allen PM.

Sci Immunol. 2019 Feb 8;4(32). pii: eaau9079. doi: 10.1126/sciimmunol.aau9079.


Intestinal Dysmotility Syndromes following Systemic Infection by Flaviviruses.

White JP, Xiong S, Malvin NP, Khoury-Hanold W, Heuckeroth RO, Stappenbeck TS, Diamond MS.

Cell. 2018 Nov 15;175(5):1198-1212.e12. doi: 10.1016/j.cell.2018.08.069. Epub 2018 Oct 4.


Interaction between smoking and ATG16L1T300A triggers Paneth cell defects in Crohn's disease.

Liu TC, Kern JT, VanDussen KL, Xiong S, Kaiko GE, Wilen CB, Rajala MW, Caruso R, Holtzman MJ, Gao F, McGovern DP, Nunez G, Head RD, Stappenbeck TS.

J Clin Invest. 2018 Nov 1;128(11):5110-5122. doi: 10.1172/JCI120453. Epub 2018 Oct 15.


Temporal Regulation of the Bacterial Metabolite Deoxycholate during Colonic Repair Is Critical for Crypt Regeneration.

Jain U, Lai CW, Xiong S, Goodwin VM, Lu Q, Muegge BD, Christophi GP, VanDussen KL, Cummings BP, Young E, Hambor J, Stappenbeck TS.

Cell Host Microbe. 2018 Sep 12;24(3):353-363.e5. doi: 10.1016/j.chom.2018.07.019. Epub 2018 Aug 16.


Abnormal Small Intestinal Epithelial Microvilli in Patients With Crohn's Disease.

VanDussen KL, Stojmirović A, Li K, Liu TC, Kimes PK, Muegge BD, Simpson KF, Ciorba MA, Perrigoue JG, Friedman JR, Towne JE, Head RD, Stappenbeck TS.

Gastroenterology. 2018 Sep;155(3):815-828. doi: 10.1053/j.gastro.2018.05.028. Epub 2018 May 18.


The microbial metabolite desaminotyrosine protects from influenza through type I interferon.

Steed AL, Christophi GP, Kaiko GE, Sun L, Goodwin VM, Jain U, Esaulova E, Artyomov MN, Morales DJ, Holtzman MJ, Boon ACM, Lenschow DJ, Stappenbeck TS.

Science. 2017 Aug 4;357(6350):498-502. doi: 10.1126/science.aam5336.

The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. Kaiko GE, Ryu SH, Koues OI, Collins PL, Solnica-Krezel L, Pearce EJ, Pearce EL, Oltz EM, Stappenbeck TS
Cell. 2016 Nov 3;167(4):1137. doi: 10.1016/j.cell.2016.10.034


Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation.

Moon C, Baldridge MT, Wallace MA, D CA, Burnham, Virgin HW, Stappenbeck TS. 
Nature. 2015 May 7;521(7550):90-93. doi: 10.1038/nature14139. Epub 2015 Feb 16

08/17/2021 |  

Researchers Develop New Model to Test Mechanisms of Penetrating Fibrosis

Researchers led by Thaddeus Stappenbeck, MD, PhD, chair of the Department of Inflammation & Immunity, have developed a new preclinical model with features of mesenteric fibrosis that are similar to what is found in Crohn’s disease patients (CD). Using clinical data coupled with the new model may help researchers identify new therapeutic targets to prevent or treat fibrosis in CD. 

05/18/2021 |  

Western Diet Impairs Function of Immune Cells in the Gut

According to new study results, a team of researchers from multiple institutions and led by Cleveland Clinic’s Thaddeus Stappenbeck, MD, PhD, have found that a diet high in fat and sugar is associated with impaired intestinal immune cell function in mice. The findings, published in Cell Host & Microbe, provide novel insights into pathways linking obesity and disease-driving gut inflammation, and have implications for developing targets to treat inflammatory bowel diseases (IBD) in patients.

03/11/2021 |  

New Evidence of Microbial Infection That Impairs Healing in Crohn’s Disease

Researchers have characterized a new tissue infection in patients with Crohn’s disease (CD) and preclinical disease models. According to new study results published in Science, the yeast Debaryomyces hansenii—commonly found in foods such as cheese and processed meat—is significantly enriched in areas of intestinal injury in preclinical models and CD patients, a discovery that may point to new treatment or prevention approaches for the common inflammatory bowel disease.

12/16/2019 |  

New Chair Named for Department of Inflammation & Immunity

Thaddeus (Thad) Stappenbeck, MD, PhD, joins Lerner Research Institute as the newly appointed Chair of the Department of Inflammation & Immunity. A digestive disease expert, he will lead a department of more than 50 principal investigators studying the origins and manifestations of a range of diseases, including infectious, autoimmune, and inflammatory diseases like asthma and transplant rejection.