Scott A. Oakes, MD

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Scott A. Oakes, MD

Associate Professor of Pathology, UCSF

scott.oakes@ucsf.edu

Phone: (415) 476-1777, 514-3165 (voice)
Box 0511, UCSF
San Francisco, CA 94143-0511

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Cancer Center Membership

Program Member » Non-aligned

Research Summary

I am a board-certified pathologist and cell biologist studying how mammalian cells sense and respond to protein-folding stress within the endoplasmic reticulum (ER) through an ancient signaling pathway called the Unfolded Protein Response (UPR), and what goes wrong with this process in diseases of cell loss (e.g., neurodegeneration, diabetes) and cell gain (e.g., cancer). To this end, we have developed rigorous in vitro assays and mouse models to identify and monitor the pro-survival and pro-death signals sent from the master UPR regulator IRE1, an ER transmembrane kinase/RNase. We designed a novel class of IRE1 inhibitors (KIRAs for Kinase Inhibiting RNase Attenuators) that shuts down its RNase allosterically through the adjacent kinase domain, and showed that they have cytoprotective benefits in pre-clinical models of retinal degeneration and diabetes. Using these genetic, chemical-genetic, and pharmacological tools, we are testing the effects of modulating the UPR in models of pancreatic neuroendocrine tumors (PanNETs) and myeloma, highly secretory solid tumors prone to protein-folding stress.

Education

Elmira College, Elmira, NY, B.A., 1993, Biochemistry
University of Connecticut, Farmington, CT, M.D., 1998, Medicine


Professional Experience

  • 1995-1996
    Research Scholar, HHMI, Lymphocyte Cell Biology Section, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD. Advisor: John J. O'Shea, M.D.
  • 1998-2000
    Resident, Anatomic Pathology, Brigham and Women's Hospital, Boston, MA
  • 1998-2002
    Clinical Fellow in Pathology, Harvard Medical School, Boston, MA
  • 2000-2005
    Research Associate, Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, MA. Advisor: Stanley J. Korsmeyer, M.D.
  • 2002-2005
    Instructor in Pathology, Harvard Medical School, Boston, MA.
  • 2005-2012
    Assistant Professor, Department of Pathology, University of California San Francisco
  • 2012-present
    Associate Professor (tenured), Department of Pathology, University of California San Francisco

Honors & Awards

  • 1989
    Salutatorian Scholarship
  • 1990
    Borden Highest Freshman GPA Prize
  • 1991
    Phi Beta Kappa Prize
  • 1992
    Phi Beta Kappa Prize
  • 1992
    Gorman Prize for Most Scholarly Work in Chemistry
  • 1993
    Outstanding Senior Chemistry Award
  • 1993
    Elmira College Valedictorian
  • 1998
    American Endocrine Society Award
  • 1998
    American Endocrine Society Award
  • 2000-2003
    NIH Pathology Training Grant Recipient
  • 2003-2008
    NIH Mentored Clinical Scientist Development Award (K08)
  • 2006-2007
    American Cancer Society Junior Investigator Award
  • 2007-2011
    HHMI Early Career Physician Scientist Award
  • 2012-2015
    American Cancer Society Research Scholar
  • 2013-2015
    Harrington Discovery Institute Scholar-Innovator Award
  • 2013
    Inductee—American Society for Clinical Investigation (ASCI)

Selected Publications

  1. Fas-Activated Mitochondrial Apoptosis Culls Stalled Embryonic Stem Cells to Promote Differentiation. Curr Biol. 2015 Dec 7; 25(23):3110-8.
    View on PubMed
  2. Erratum: Proteostasis control by the unfolded protein response. Nat Cell Biol. 2015 Jul 31; 17(8):1088.
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  3. Proteostasis control by the unfolded protein response. Nat Cell Biol. 2015 Jun 30; 17(7):829-38.
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  4. CDK1 Inhibition Targets the p53-NOXA-MCL1 Axis, Selectively Kills Embryonic Stem Cells, and Prevents Teratoma Formation. Stem Cell Reports. 2015 Mar 10; 4(3):374-89.
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  5. Suppression of epithelial-mesenchymal transition and apoptotic pathways by miR-294/302 family synergistically blocks let-7-induced silencing of self-renewal in embryonic stem cells. Cell Death Differ. 2015 Jul; 22(7):1158-69.
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  6. The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol. 2015 Jan 24; 10:173-94.
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  7. Immune evasion mediated by tumor-derived lactate dehydrogenase induction of NKG2D ligands on myeloid cells in glioblastoma patients. Proc Natl Acad Sci U S A. 2014 Sep 2; 111(35):12823-8.
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  8. Allosteric inhibition of the IRE1a RNase preserves cell viability and function during endoplasmic reticulum stress. Cell. 2014 Jul 31; 158(3):534-48.
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  9. Golgi fragmentation precedes neuromuscular denervation and is associated with endosome abnormalities in SOD1-ALS mouse motor neurons. Acta Neuropathol Commun. 2014; 2:38.
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  10. Divergent allosteric control of the IRE1a endoribonuclease using kinase inhibitors. Nat Chem Biol. 2012 Dec; 8(12):982-9.
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  11. IRE1a cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science. 2012 Nov 9; 338(6108):818-22.
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  12. IRE1a induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab. 2012 Aug 8; 16(2):250-64.
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  13. Dual blockade of lipid and cyclin-dependent kinases induces synthetic lethality in malignant glioma. Proc Natl Acad Sci U S A. 2012 Jul 31; 109(31):12722-7.
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  14. The adaptor protein CRK is a pro-apoptotic transducer of endoplasmic reticulum stress. Nat Cell Biol. 2012 Jan; 14(1):87-92.
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  15. Multiple defects, including premature apoptosis, prevent Kaposi's sarcoma-associated herpesvirus replication in murine cells. J Virol. 2012 Feb; 86(3):1877-82.
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  16. Signaling cell death from the endoplasmic reticulum stress response. Curr Opin Cell Biol. 2011 Apr; 23(2):143-9.
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  17. Akt and autophagy cooperate to promote survival of drug-resistant glioma. Sci Signal. 2010; 3(147):ra81.
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  18. Blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function in a mouse model of amyotrophic lateral sclerosis. J Clin Invest. 2010 Oct; 120(10):3673-9.
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  19. IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell. 2009 Aug 7; 138(3):562-75.
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  20. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol Cell Biol. 2008 Jun; 28(12):3943-51.
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