See all

Thaddeus Stappenbeck, MD, PhD

Conan Professor, Pathology & Immunology
Co-Chief, Division of Laboratory and Genomic Medicine

Phone314-362-4214

Fax314-362-7487

Emailstappenb@wustl.edu

Additional Titles

  • Professor, Developmental Biology

Education

  • BA, Integrated Science program Physiology: Northwestern University, Evanston, IL (1987)
  • MD, PhD, Medical Scientist Training Program (MSTP): Northwestern University, Evanston, IL (1995)
  • Resident, Anatomic Pathology: Washington University Medical Center, St. Louis, MO (1995-1999)
  • Clinical Fellow, Pathology: Washington University Medical Center, St. Louis, MO (1999-2000)

Board Certifications

  • State of Missouri (108584)
  • American Board of Anatomic Pathology

Recognition

  • 1987 Phi Beta Kappa
  • 1992 Sigma Xi Research Award
  • 1993 Journal of Cell Science Travel Fellowship to visit laboratory of Dr. Birgit Lane
  • 1993 International Union of Pure and Applied and Biophysicists Travel Fellowship
  • 2001 Laser Capture Microdissection and Macromolecular Analysis of Normal Development and Pathology Travel Award
  • 2005 Pew Scholar
  • 2009 American Society for Clinical Investigation
  • 2010 Kavli Fellow
  • 2010 Pluto Society
  • 2012 American Gastroenterological Association (AGA) Fellowship
  • 2013 Organizer, Gastrointestinal Tract XV: Epithelia, Microbes, Inflammation and Cancer August 11-15, 2013 Steamboat Colorado (FASEB conference)
  • 2015 Chair Senior Research Awards Study Section, Crohn’s & Colitis Foundation
  • 2016 Editorial Board, Science Immunology
  • 2016 Crohn’s & Colitis Foundation Scientific Achievement in IBD Basic Science Award
  • 2017 American Association of Physicians

Clinical Interests

  • Pathogenesis of inflammatory bowel disease

Research Interests

Organs such as the lung and intestine with large surface areas, critical for their absorptive capacity, must also maintain an effective barrier to the outside world. My lab focuses on emerging aspects of innate mucosal immunology that maintain homeostasis and correct injuries at these interfaces. A major focus of the lab is the single layer of epithelial lining cells that forms the absorptive barrier in mucosa-lined organs. An important concept that has grown out of our work, mostly through analysis of mouse models using genetic, pharmacologic, and physical injury is that the decisions made by the epithelium are driven in large part by communication apically through contact with microbes and baso-laterally through contact with their underlying immune and stromal cell populations. We have recently developed novel methods to culture, expand and differentiate epithelial stem cells from mucosal surfaces of mice and humans. These new experimental systems now allow us to study the interactions of epithelial cells with microbes and other host cells to uncover the details of these conversations. Importantly, we can now perform these studies with human cells taken from biopsy specimens which will facilitate translational studies of specific human diseases such as inflammatory bowel disease where mucosal homeostasis is not maintained.

Examples of current projects in the lab that are examining this paradigm: 1) the delineation of how specific commensal bacteria and their gene products trigger inflammation in a genetically susceptible host, 2) understanding the mechanism of how viral infection alters epithelial cell turnover, 3) determining how genes involved in the genetic susceptibility of inflammatory bowel disease function in the epithelium during and how their altered function can lead to disease. One surprise here is that proteins in the autophagy pathway play an important role in epithelial secretion of mucus and antimicrobial proteins in both lung airways and gut. 4) We also study how the host shapes intestinal microbial communities through secretion of IgA and antimicrobial proteins. 5) We are defining previously unrecognized cells and structures that play a key role in repair.  We are interested in the first cellular responders to mucosal damage in the form of wound associated epithelial (WAE) cells as well as expanded active stem cells the form wound channels which are precursors to new crypt formation.

DBBS Graduate Program Affiliation

  • Developmental Biology Program
  • Molecular Cell Biology Program
  • Immunology Program

Publications

pubmed search

The Microbial Metabolite Desa 1 minotyrosine Protects from Influenza through Type I Interferon Ashley L. Steed, George P. Christophi, Gerard E. Kaiko, Lulu Sun, Victoria Goodwin, Ekaterina Esaulova, Maxim N. Artyomov, David J. Morales, Deborah J. Lenschow, Thaddeus S. Stappenbeck. Science (in press)
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 Jun 16;165(7):1708-20.
Accounting for reciprocal host-microbiome interactions in experimental science. Stappenbeck TS, Virgin HW. Nature. 2016 Jun 9;534(7606):191-9.
Prostaglandin E2 promotes intestinal repair through an adaptive cellular response of the epithelium. Miyoshi H, VanDussen KL, Malvin NP, Ryu SH, Wang Y, Sonnek NM, Lai CW, Stappenbeck TS. EMBO J. 2017 Jan 4;36(1):5-24.
Mucosally transplanted mesenchymal stem cells stimulate intestinal healing by promoting angiogenesis. Manieri NA, Mack MR, Himmelrich MD, Worthley DL, Hanson EM, Eckmann L, Wang TC, Stappenbeck TS. J Clin Invest. 2015 Sep;125(9):3606-18.
Colitogenic Bacteroides thetaiotaomicron Antigens Access Host Immune Cells in a Sulfatase-Dependent Manner via Outer Membrane Vesicles. Hickey CA, Kuhn KA, Donermeyer DL, Porter NT, Jin C, Cameron EA, Jung H, Kaiko GE, Wegorzewska M, Malvin NP, Glowacki RW, Hansson GC, Allen PM, Martens EC, Stappenbeck TS. Cell Host Microbe. 2015 May 13;17(5):672-80.
Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation. Moon C, Baldridge MT, Wallace MA, Burnham CA, Virgin HW, Stappenbeck TS. Nature. 2015 May 7;521(7550):90-3.
Type I interferons link viral infection to enhanced epithelial turnover and repair. Sun L, Miyoshi H, Origanti S, Nice TJ, Barger AC, Manieri NA, Fogel LA, French AR, Piwnica-Worms D, Piwnica-Worms H, Virgin HW, Lenschow DJ, Stappenbeck TS. Cell Host Microbe. 2015 Jan 14;17(1):85-97.
Development of an enhanced human gastrointestinal epithelial culture system to facilitate patient-based assays. VanDussen KL, Marinshaw JM, Shaikh N, Miyoshi H, Moon C, Tarr PI, Ciorba MA, Stappenbeck TS. Gut. 2015 Jun;64(6):911-20.
Wnt5a potentiates TGF-β signaling to promote colonic crypt regeneration after tissue injury. Miyoshi H, Ajima R, Luo CT, Yamaguchi TP, Stappenbeck TS. Science. 2012 Oct 5;338(6103):108-13.


Assistant
Ann Winn
314-454-8436
awinn@wustl.edu

Lab Phone: 314-362-4249
Office Location: CSRB, North Tower, Room 1029