Andrew Oberst, Ph.D.

Andrew Oberst, Ph.D.

Assistant Professor, Immunology

Dr. Andrew Oberst graduated from Amherst College in 2001, and pursued his graduate studies in Europe, in a collaborative program between the Universities of Rome and Paris.   He received his Doctorate in 2006, then completed postdoctoral training at St. Jude Children’s Research Hospital in Memphis, TN.  He joined the Department of Immunology as an Assistant Professor in 2012.

Contact Info

Department of Immunology
University of Washington
Office E306, Box 358059
750 Republican Street
Seattle WA 98109-8059
Phone: 206-221-7316
Fax: 206-616-4274

Research Areas

  • Cancer Immunology
    Infectious Diseases
    Innate Immunity

LAB

Pubmed

Andrew Oberst, PhD

Research in the Oberst lab focuses on understanding how different forms of cell death occur, and how they influence immune responses in vivo. Multicellular organisms are complex communities cooperating of cells, and the death of some cells is required for the community to survive and thrive.  It has classically been thought that cells can die in one of two way:  Necrosis is a passive form of cell death, which occurs in response to overwhelming damage, while apoptosis is a regulated form of cellular suicide that is carried out by specific proteins in response to discrete stimuli.  Importantly, necrotic cell death involves cellular rupture and the release of potentially damaging cellular contents into surrounding tissue, leading to inflammation.  Apoptosis, by contrast, is an ordered process of cellular disposal in which cells are disassembled, packaged, and rapidly eliminated by phagocytes; it is therefore non-immunogenic in most circumstances.

Recently, the dichotomy between necrosis and apoptosis has become more complicated, with the description of an additional form of cell death called programmed necrosis.  As its name implies, programmed necrosis is executed by specific proteins that have evolved for this purpose; however, it is morphologically similar to necrosis, in that it involves cellular swelling and rupture and is therefore immunogenic.  Programmed necrosis can be triggered by members of the TNF receptor superfamily, as well as by TLRs and other innate immune receptors.  Intriguingly, many of these same signals can also initiate proliferation or drive apoptotic cell death, depending on the cellular circumstances in which they occur. 

The Oberst lab focuses on understanding how these pleiotropic signals lead to cellular survival, apoptosis, or programmed necrosis, and how each outcome influences immune responses.   We use cell biology and biochemistry techniques to study how apoptosis and programmed necrosis are initiated, and to create systems in which each form of cell death can be specifically triggered.  We then use these tools to study the effect of each type of cell death in vivo, with the goal of understanding their role in processes such as inflammation, autoimmunity, tumor suppression, and immune responses to pathogen infection.

1. Weinlich, R., Oberst, A., Dillon, C.P., Janke, L.J., Milasta, S., Lukens, J.R., Rodriguez, D.A., Gurung, P., Savage, C., Kanneganti, T.D., Green, D.R. 'Protective roles for caspase-8 and cFLIP in adult homeostatis' Cell Reports (in press)

2. Oberst, A. 'Autophagic cell death RIPs into tumors' Cell Death Differ, 2013, Sep;20(9):1131-2

3.  
Dillon CP, Oberst A, Weinlich R, Janke LJ, Kang TB, Mak TW, Wallach D, Green DR. 'Survival function of the FADD-Caspase8-FLIP complex' Cell Reports. 2012 May 31;1(5):401-7

4.    O’Donnell MA, Perez-Jimenez E, Oberst A, Ng A, Massoumi R, Xavier R, Green DR, Ting AT. Caspase-8 inhibits programmed necrosis by processing CYLD. Nat Cell Biol 2011 Oct 30;13(12):1437-42

5.   
Martinez J, Almendinger J, Oberst A, Ness R, Dillon CP, Fitzgerald P, Hengartner MO, Green DR. LC3-associated phagocytosis is required for the efficient clearance of dead cells. Proc Natl Acad Sci 2011 108(42): 17396-401

6.   
Oberst A, Dillon CP, Weinlich R, McCormick LL, Fitzgerald P, Pop C, Hakem R, Salvesen GS, Green DR. Catalytic activity of the caspase-8-FLIPL complex inhibits RIPK3-dependent necrosis. Nature 2011 471, 363-367

7.   
Pop C*, Oberst A*, Drang M, Van Raam BJ, Riedl SJ, Green DR, Salvesen GS. FLIPL induces caspase-8 activity in the absence of interdomain caspase-8 cleavage and alters substrate specificity. Biochem J. 2011 Jan 14;443(3):447-57 

8.   
Oberst A*, Pop, C*, Tremblay AG, Blais V, Denault JB, Salvesen GS, Green DR. Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation. J Biol Chem. 2010 May 28;285(22):16632-42 

B.A., Biology,  Amherst Colege
Ph.D., Biochemistry and Molecular Biology, Universitá di Tor Vergara (Rome) & Université Pierre et Marie Curie (Paris)
 

Graduate Students
Michelle Brault, mrb318@uw.edu
Susana Orozco, slorozco@uw.edu

Postdoctoral Fellows
Kim Gutierrez, gutiedkd@uw.edu

Laboratory Staff
Margo Werner, margow@uw.edu