Deborah L. Gumucio, Ph.D.
Professor, Department of Cell and Developmental Biology
Co-Director, Center for Organogenesis
109 Zina Pitcher Place
2045 Biomedical Sciences Research Bldg (BSRB)
(734) 647-0172
Email: dgumucio@umich.edu

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Publications listed on PubMed
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Research in the Gumucio lab is focused on two general topics:

Molecular etiology of Familial Mediterranean fever (FMF)

FMF is an autoinflammatory disorder characterized by recurrent attacks of fever with localized pain, generally in abdomen, chest, or joint. It is caused by mutations in the pyrin, a protein expressed in neutrophils and monocytes, white blood cells that are important in the inflammatory response. Normally, pyrin is thought to act as a negative regulator of the inflammatory response. How it does so (and why mutant forms of pyrin fail to do so) are questions studied in our laboratory.

1. The International FMF consortium (Group 4 [of 6]: Richards, N., Shelton, D.A., and Gumucio, D.) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell. 90:797-807, 1997.
   
   
2. Richards, N., Schaner, P., Diaz, A., Stuckey, J., Wadhwa, A., and Gumucio, D.L. The N-terminus of pyrin encodes a death domain-related structure that interacts with apoptosis speck protein (ASC) and accelerates apoptosis. J. Biol. Chem. 276:39320-39329, 2001.
   
   
3. Schaner, P., Richards, N., Wadhwa, A., Aksentijevich, I., Kastner, D., Tucker, P. and Gumucio, D.: Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states. Nature Genetics 27:318-321, 2001.
   
   
4. Gumucio, D.L., Diaz, A., Schaner, P., Richards, N., Babcock, C., Schaller, M. and Cesena, T.: Fire and ICE: The role of pyrin domain-containing proteins in inflammation and apoptosis. Clin. Exp. Rheumatol. 20:S45-S53, 2002.
   
   
5. Schaner, P. and Gumucio, D.L.: Familial Mediterranean fever in the post-genomic era (How an ancient disease is providing new insights into inflammatory pathways). Invited review. Current Drug Targets-Inflammation and Allergy. In Press, 2004.
   
   
6. Diaz, A., Hu, C., Kastner, D.L., Schaner, P., Reginato, A.M., Richards, N., and Gumucio, D.L.: Expression of multiple alternatively spliced MEFV transcripts in human synovial fibroblasts induced by lipopolysaccharide. In Press, Arthritis and Rheumatism, 2004. Supplemental Figures

Cell: cell communication during development of the small intestine and stomach

The goal of this project is to learn more about how the intestine develops its characteristic structures (crypts and villi). We identified a region of the villin promoter that happens to be an outstanding tool for the expression of a variety of transgenes in the intestinal epithelium. We have now used this promoter to drive inhibitors of a variety of signaling proteins involved in epithelial/mesenchymal interactions during gut development. In this way, we have identified new roles for the hedgehog pathway in late intestinal morphogenesis. In addition, we are trying to understand how an intestinal cell “decides” to be intestine rather than stomach. The process that regulates this identity decision may be altered in cases of intestinal metaplasia, lesions of the stomach in which the stomach epithelium takes on the appearance of intestine. Intestinal metaplasia is associated with the development of gastric cancer, making this identity program a critical target for further research.

1. Pinson, K., Dunbar, L., Samuelson, L.C. and Gumucio, D.L.: Targeted disruption of the mouse villin gene does not impair the morphogenesis of microvilli. Devel. Dynam., 211:109-121, 1998.
   
   
2. Braunstein, E.M., Qiao, T., Madison, B., Pinson, K. Dunbar, L., and Gumucio, D.L. Villin: a marker for development of the epithelial pyloric border. Dev. Dyn. 224:90-102, 2002.
   
   
3. Madison, B., Qiao, T., Braunstein, E., Dunbar, L., and Gumucio, D.L Cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine. J Biol Chem. 277:33275-33283, 2002.
   
   
4. Madison, B., Braunstein, K., Qiao, X., Kuizon, E., and Gumucio, D.: Hedgehog signals pattern the intestinal crypt-villus axis. Development (Submitted, September 2004).
   
   
5. Rieder, G., Tessier, A.J., Qiao, X.T., Madison, B., Gumucio, D. and Merchant, J.L.: Helicobacter-induced intestinal metaplasia in the stomach correlates with Elk-1 and serum response factor induction of villin. Gastroenterology, (Submitted, September 2004).

(In short, we do Blood and Guts research!)