Welcome to the Thompson-Snipes' Lab
LuAnn Thompson-Snipes, Ph.D. (photo)
Ph.D. Vanderbilt University, Nashville, TN
Post-doctoral fellow DNAX Research
Institute of Immunology and Molecular Biology, Palo Alto, CA
Inflammatory bowel disease (IBD) is an idiopathic, often debilitating disorder that carries a significantly increased risk for the development of colorectal carcinoma. Adequate long-term treatment remains elusive. Approximately 1.4 million people in the U.S. have IBD. Marked inflammation of the distal digestive system is the pathologic hallmark of the disease. Immune dysregulation with abnormal interactions between the mucosal immune system and the gut flora is the likely general mechanism for IBD. Specific cellular and molecular mechanisms underlying IBD are incompletely understood although several animal models have been studied. It is clear that there are environmental and genetic components to IBD. However, susceptibility to IBD cannot be accounted for by simple mendelian genetics. Complex gene interactions appear to occur in IBD.
Our lab is examining the role of dendritic cells (DCs) in the development of IBD in mice lacking the inhibitory regulatory subunit, , associated with a subset of G-protein linked receptors. Though a relatively complex model for IBD owing to the involvement of G-protein linked receptors in a wide array of cell types and signaling pathways, the deficient mice provide a well-characterized, reproducible model for identifying novel mechanisms that may modulate the development or treatment of IBD. Gαi2 deficient mice, like humans, spontaneously develop an ulcerative colitis-like disease that frequently progresses to adenocarcinoma (Rudolph, U. et al. 1995. Nature Genetics, 10:143-150). The genetic background is important: Gαi2-/- 129/SvEv and Gαi2-/- BALBc mice develop colitis whereas Gαi2-/- C57BL/6 mice remain clinically healthy. Our lab is currently focusing on the DC because, by virtue of it's antigen-presentation and immune modulatory functions, their dysfunction could contribute substantially to the development of IBD. Conversely, these same DC functions could be co-opted to modulate the inflammatory process to effect a treatment.
Related Publications:
Thompson-Snipes L, Cox B, Carter L, Lei C, Finegold M. Gastrointestinal Endoscopy, 57 (5): AB216-AB216 Suppl. 1, APR 2003.
Chagnon F, Tanguay S, Ozdal O L, Guan M, Ozen ZZ, Ripeau S, Chrevrette M, Elhilali MM,Thompson-Snipes L. Potentiation of a Dendritic Cell Vaccine for Murine Renal Cell Carcinoma by CpG Oligonucleotide, manuscript accepted in Clinical Cancer Research, 2005.
Thompson-Snipes L, E Skamene, and D Radzioch. Acquired but not innate resistance to Mycobacterium bovis Bacillus Calmette-Guerin is compromised by Interleukin-12 ablation. Infect. and Immun. 66:5268-5274, 1998.
Berg D J, Davidson N, Kuhn R, Muller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, and Rennick D. Enterocolitis and colon cancer in IL-10 deficient mice are associated with aberrant cytokine production and CD4(+) Th1-like responses. J. Clin. Invest. 98:1010-1020, 1996.