Please note: The University of Texas Health Science Center at San Antonio will now be called "UT Health San Antonio."

Search Program Faculty/Research

William Kaiser, Ph.D.

Kaiser

RESEARCH

Dr. William Kaiser's research program focuses on the host defense role of programmed cell death (apoptosis and necroptosis). 

Our studies demonstrate that programmed necrosis functions as a critical defense against viral infection; however, dysregulated necroptosis results in lethal inflammation in mice and understanding this process may reveal therapeutic strategies to treat chronic inflammatory diseases. Though once regarding as an unregulated pathological endpoint, necrosis can be orchestrated by the activity of a protein complex composed of the kinases RIP1 and RIP3. A number of cell stress and host defense pathways prime cells for necroptosis, and in the context of viral infection, elimination of infected cells benefits the host. In contrast, dysregulated pronecrotic kinase activity leads to vasculature defects, collapse in hematopoiesis, and lethal skin and gut inflammation. 

These findings suggest necroptosis may drive a spectrum of disease states, thus elevating expectations for therapies targeting necrotic cell death. At present, the pathways engaged by RIP1/RIP3 to induce necrosis remain incomplete. To define the molecular basis of necroptosis, we will (1) characterize the signal transduction pathways upstream and downstream of RIP1/ RIP3, (2) identify new programmed necrosis signaling components, (3) develop strategies for therapeutic intervention, and (4) extend these finding to genetic mouse models of disease caused by excessive cell death.

Selected Publications

Guo H, Omoto S, Bertin JS, Gough PJ, Kaiser WJ*, Mocarski ES*. (2015) Herpes Simplex Virus R1 Suppresses Necroptosis. Cell Host & Microbe. 17, 243-251.

MandalP, BergerSB, PillayS, MoriwakiK, HuangC, Guo H, LichJD, FingerJ, KasparcovaV, VottaB, OuelletteM, KingBW, WisnoskiD, Lakdawala AS, DeMartinoMP, Casillas LN, HailePA, SehonCA, MarquisRW, UptonJW, RobackL, RamiaN, DoveyCM, Carette J, ChanF, BertinJS, GoughPJ, MocarskiES, KaiserWJ. (2014) RIP3 induces apoptosis independent of pro-necrotic kinase activity. Molecular Cell. 56: 481-495.

RickardJA, Anderton H, EtemadiN, Nachbur U,Darding M, Peltzer N, LalaouiN, LawlorKE, VanyaiH, HallC, BankovackiA, GangodaL, WongWW, CorbinJ, HuangC, Mocarski ES, MurphyJM, AlexanderWS, VossAK, VauxDL, KaiserWJ, Walczak H, Silke J(2014) TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice. eLIFE. 03464.

Kaiser WJ, Daley-Bauer LP, Thapa RJ, Mandal P, Berger SB, Huang C, Sundararajan A, Guo H, Roback L, Speck SH, Bertin JS, Gough PJ, Balachandran S, Mocarski MS. (2014) RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition. Proceedings of the National Academy of Sciences of the United States of America. 111: 7753-7758.

Berger SB, Kasparcova V, Hoffman S, Swift B, Dare L, Schaeffer M, Capriotti C, Cook M, Finger J, Hughes-Earle A, Harris PA, Kaiser WJ, Mocarski ES, Bertin JS, Gough PJ (2014) Cutting Edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice. Journal of Immunology. 192: 5476-5480.

Upton JU, Kaiser WJ, Mocarski ES. (2012) DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host & Microbe. 11: 290-297.

Kaiser WJ, UptonJW, Long AB, Livingston-Rosanoff D, Daley LP, Hakem R, Caspary T, Mocarski ES. (2011) RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature. 471(7338): 368-372.

Mocarski ES, Upton JU, Kaiser WJ. (2011) Viral infection and the evolution of capase-8 regulated apoptotic and necrotic death pathways. Nature Reviews Immunology. 12: 79-88.

Upton JW*, Kaiser WJ*, Mocarski ES. (2010) Virus Inhibition of RIP3-dependent Necrosis. Cell Host & Microbe. 7: 302-13.

* authors contributed equally

corresponding author

Associate Professor

Department of Microbiology, Immunology, and Molecular Genetics

Education

Ph.D., Microbiology and Immunology, Emory University, 2012

A.B. & B.S., English and Cell Biology, University of Georgia, 1998

Contact

Room 5.020V

Phone: (210) 567-0706

Email. kaiserw@uthscsa.edu