Thaddeus  Stappenbeck,  MD, PhD

Thaddeus Stappenbeck, MD, PhD

Chair

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

Dr. Stappenbeck’s team has found interconnectivity between inflammatory fibroblasts and the molecular features of penetrating fibrosis in Crohn’s disease.




05/18/2021 |  

Western Diet Impairs Function of Immune Cells in the Gut

Preclinical findings from Dr. Stappenbeck show that a western diet damages the immune system in the gut, which can lead to chronic inflammation and could increase the risk of inflammatory bowel disease.




03/11/2021 |  

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

Dr. Stappenbeck and his team found that the yeast D. hansenii, a type of fungus, is elevated in models of Crohn’s disease, particularly concentrated within intestinal wounds, suggesting that targeting this infection may be a viable approach to treat or prevent the disease.