ENVIRONMENTAL HEALTH SCIENCES RESEARCH CENTER
A National Institute of Environmental Health Sciences Center of Excellence

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EHSRC Investigator Detail

The focus of Dr. Sutterwala's research is a recently described family of molecules called NLRs (NOD-like receptors) which are involved in regulation of innate immune responses and cell death pathways. Some NLR family members have been shown to promote the activation of proinflammatory caspases within multiprotein complexes called inflammasomes. Mutations within NALP3, a member of the NLR family, have been linked to a group of autoinflammatory disorders in humans collectively known as the Cryopyrin-associated periodic syndromes. IPAF, another NLR family member, has been shown to play a crucial role in response to infection with a number of Gram-negative bacteria. To understand the role of NLRs in coordinating the immune response we have used a gene-targeting approach utilizing mice deficient in specific inflammasome components. We are interested in characterizing the signaling events involved in activation of the NALP3- and IPAF-inflammasomes, as well as determining the role of these inflammasomes in murine models of autoinflammatory and infectious disease and correlating this to disease pathogenesis in humans.

Selected Publications

1. Cassel, S.L., S.C. Eisenbarth, S.S. Iyer, J.J. Sadler, O.R. Colegio, L.A. Tephly, A.B. Carter, P.B. Rothman, R.A. Flavell, and F.S. Sutterwala. 2008. The Nalp3 inflammasome is essential for the development of silicosis. Proc. Natl. Acad. Sci. U.S.A. 105:9035-9040.
   
2. Eisenbarth, S.C., O.R. Colegio, W. O’Connor, F.S. Sutterwala, and R.A. Flavell. 2008. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminum adjuvants. Nature. 453:1122-1126.
   
3. Sutterwala, F.S., and R.A. Flavell RA. 2008. Immunology: cascade into clarity. Nature. 451:254-255. (News and Views)
   
4. Sutterwala, F.S., L.A. Mijares, L. Li, Y. Ogura, B.I. Kazmierczak, and R.A. Flavell. 2007.Immune recognition of Pseudomonas aeruginosa is mediated by the IPAF inflammasome. J. Exp. Med. 204:3235-3245.
   
5. Pedra, J.H., F.S. Sutterwala, B. Sukumaran, Y. Ogura, F. Qian, R.R. Montgomery, R.A. Flavell, and E. Fikrig. 2007. ASC/PYCARD and caspase-1 regulate the IL-18/IFNg axis during Anaplasma phagocytophilum infection. J. Immunol. 179:4783-4791.
   
6. Sutterwala, F.S., Y. Ogura, and R.A. Flavell. 2007. The inflammasome in pathogen
   recognition and inflammation. J. Leukocyte Biol. 82:259-264.
   
7. Ogura, Y., F.S. Sutterwala, and R.A. Flavell. 2006. The inflammasome: first line of the
   immune response to cell stress. Cell. 126:659-662.
   
8. Lara-Tejero, M, F.S. Sutterwala, Y. Ogura, E.P. Grant, J. Bertin, A.J. Coyle, R.A. Flavell, and J.E. Galán. 2006. Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis. J. Exp. Med. 203:1407-1412.
   
9. Sutterwala, F.S., Y. Ogura, M. Szczepanik, M. Lara-Tejero, G.S. Lichtenberger, E.P.
   Grant, J. Bertin, A.J. Coyle, J.E. Galán, P.W. Askenase, and R.A. Flavell. 2006. Critical
   role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation
   of caspase-1. Immunity. 24:317-327.
   
10. Laouar, Y., F.S. Sutterwala, L. Gorelik, and R.A. Flavell. 2005. TGFb controls TH1
    development through regulation of NK cell IFNg. Nat. Immunol. 6:600-607.
    
11. Yarovinsky, F., D. Zhang, J.F. Andersen, G.L. Bannenberg, C.N. Serhan, M. S. Hayden, S. Hieny, F.S. Sutterwala, R.A. Flavell, S. Ghosh, and A. Sher. 2005. A profilin-like protein from Toxoplasma gondii potently triggers dendritic cell IL-12 production through TLR11. Science. 308:1626-1629.

  Environmental Health Sciences Research Center, The University of Iowa, 100 Oakdale Campus, #178 IREH, Iowa City, IA 52242

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