UPTON, JASON

Jason Upton

Assistant Professor
Molecular Biosciences


Programmed cell death in viral pathogenesis and disease
upton@austin.utexas.edu

Phone: 512-475-6864

Office Location
NMS 3.116

Postal Address
The University of Texas at Austin
Molecular Biosciences, College of Natural Sciences
2506 Speedway
Austin, TX 78712

Research Summary:

Programmed cell death (PCD) serves as an efficient intrinsic defense against cellular injury or infection. Many pathogens, such as viruses, subvert normal cell death pathways as a mechanism to facilitate their own replication and persistence. Research in the Upton lab centers focuses on the molecular pathogenesis of murine cytomegalovirus (MCMV) and the regulation of PCD during infection. Using techniques of molecular and cellular biology, virology, and immunology, our research focuses on (1) elucidating the molecular mechanisms that initiate and execute programmed cell death pathways, (2) identifying and characterizing pathogen-encoded mechanisms of cell death suppression, and (3) understanding the role of cell death and cell death suppression during natural host-pathogen interactions, specifically influences on pathogenesis and host immunity.

Evasion of PCD is also a hallmark of cancer. Tumor cells develop a variety of mechanisms to subvert cell death pathways that would normally eliminate these defective cells. Therefore understanding how cell death is controlled is central to the understanding of cancer itself. The Upton lab also focuses on interrogating the molecular mechanisms by which cancer cells evade PCD. Using the understanding and insights gleaned from studying viral systems, we aim to identify and characterize how tumor cells inactivate their own cell death machinery to survive and spread, providing potential novel targets for therapeutic intervention.

Publications:

2015 Dick JE, Hilterbrand AT, Boika A, Upton JW, Bard AJ. Electrochemical detection of a single cytomegalovirus at an ultramicroelectrode and its antibody anchoring. Proc Natl Acad Sci U S A. 112(17):5303-8. PubMed PMID: 25870261.

2015 Sun C, Schattgen SA, Pisitkun P, Jorgensen JP, Hilterbrand AT, Wang LJ, West JA, Hansen K, Horan KA, Jakobsen MR, O'Hare P, Adler H, Sun R, Ploegh HL, Damania B, Upton JW, Fitzgerald KA, Paludan SR. Evasion of innate cytosolic DNA sensing by a gammaherpesvirus facilitates establichment of latent infection. J Immunol.  194(4):1819-31. PMID: 25595793.

2014 Upton JW, Chan FK.  Staying Alive: Cell Death in Antiviral Immunity. Molecular Cell. 54(2): 273-280

2014 Sridharan H, Upton JW. Programmed necrosis in microbial pathogenesis. Trends in Microbiology. 22(4): 199-207.

2014 Mocarski ES, Kaiser WJ, Livingston-Rosanoff D, Upton JW, Daley-Bauer LP. True grit: programmed necrosis in antiviral host defense, inflammation, and immunogenicity. Journal of Immunology. 192(5): 2019-26.

2013 Kaiser WJ, Sridharan H, Huang C, Mandal P, Upton JW, Gough PJ, Sehon CA, Marquis RW, Bertin JJ and Mocarski ES.  Toll-like receptor 3 induces RIP1-independent necrosis via a TRIF-RIP3 complex. J.Biol.Chem. 228(43):31268-79.

2013 Kaiser WJ, Upton JW, Mocarski ES.  Viral modulation of programmed necrosis. Current Opinions in Virology. 3(3): 296-306.

2012 Mocarski ES, Upton JW, Kaiser WJ., Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic pathways., Nature Reviews Immunology 12: 1-10

2012 Upton JW, Kaiser WJ, Mocarski ES, DAI/ZBP1/DLM-1 Complexes with RIP3 to Mediate Virus-Induced Programmed Necrosis that Is Targeted by Murine Cytomegalovirus vIRA, Cell Host & Microbe 11(3): 290-7

2011 Kaiser WJ, Upton JW, Long AB, Livingston-Rosanoff D, Daley-Bauer LP, Caspary T, Mocarski ES, RIP3 mediates the embryonic lethality of caspase-8-deficient mice., Nature 471(7338): 368-72

2010 Upton JW, Kaiser WJ, Mocarski ES, Virus inhibition of RIP3-dependent necrosis., Cell Host and Microbe 7(4): 302-13

2009 Hendrickson JE, Saakadze N, Cadwell CM, Upton JW, Mocarski ES, Hillyer CD, Zimring JC., The spleen plays a central role in primary humoral alloimmunization to transfused mHEL red blood cells, Transfusion 48(8): 1678-84

2008 Upton JW, Kaiser WJ, Mocarski ES, Cytomegalovirus M45 cell death suppression requires receptor-interacting protein (RIP) homotypic interaction motif (RHIM)-dependent interaction with RIP1, J. Biol. Chem 283(25): 16966-70

2008 Kaiser WJ, Upton JW, Mocarski ES, Receptor-interacting protein homotypic interaction motif (RHIM)-dependent control of NF-κB activation via the DNA-dependent activator of interferon regulatory factors (DAI/ZBP1/DLM-1)., J. Immunol 181(9): 6427- 34

2006 Moser JM, Farrell M, Krug LT, Upton JW, Speck SH, A Gammaherpesvirus 68 Gene 50 Null Mutant Establishes Long-Term Latency in the Lung but Fails To Vaccinate against a Wild-Type Virus Challenge, J. Virol 80(3): 1592-8

2006 Upton JW and Speck SH, Evidence for cyclin-dependent kinase (CDK)- dependent and CDK-independent functions of the murine gammaherpesvirus 68 vcyclin, J. Virol 80(24): 11946-59

2005 Moser JM, Upton JW, Gray KS, Speck SH, Ex vivo stimulation of B cells latently infected with gammaherpesvirus 68 triggers reactivation from latency, J Virol 79(8): 5227-31

2005 Moser JM, Upton JW, Allen RD 3rd, Wilson CB, Speck SH, Role of B-cell proliferation in the establishment of gammaherpesvirus latency, J Virol 79(15): 9480-91

2005 Upton JW, van Dyk LF, Speck SH, Characterization of murine gammaherpesvirus 68 v-cyclin interactions with cellular cdks, Virology 341(2): 271-83

BIO 361 - Human Infectious Disease