Research Summary
Scott Oakes’s laboratory studies how mammalian cells commit “suicide” in response to various forms of damage and what goes wrong with this process in cancer and other diseases. In particular, they focus on a type of stress that occurs when the cell’s protein folding factory—an organelle called the endoplasmic reticulum—is overwhelmed and protein quality control fails. He is actively engaged in developing drugs to control cell fate under these conditions, which have potential to benefit patients with diseases from cancer to neurodegeneration.
Keywords
Cell Death, Apoptosis, Endoplasmic Reticulum Stress, Cell Signaling, Protein Misfolding, Cancer, Neurodegenerative Disease
Education
  • Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Postdoctoral Scholar Biochemistry & Cell Biology 06/2005
  • Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Residency Pathology 06/2000
  • University of Connecticut School of Medicine, Farmington, CT, M.D. Medicine 05/1998
  • Howard Hughes Medical Institute, National Institutes of Health, Bethesda, M.D., Research Scholar Immunology 06/1996
  • Elmira College, Elmira, NY, B.A. Biochemistry 06/1993
Biosciences Graduate Program Association
Awards & Honors
  • 1993 - Valedictorian Elmira College
  • 1995 - 1996 Research Scholar Howard Hughes Medical Institute
  • 2003 - 2008 Mentored Clinical Scientist Development Award (K08) NIAMS, NIH
  • 2006 - 2007 Junior Investigator Award American Cancer Society
  • 2007 - 2011 Early Career Physician Scientist Award Howard Hughes Medical Institute
  • 2012 - 2015 Research Scholar Award American Cancer Society
  • 2013 - 2015 Scholar-Innovator Award Harrington Discovery Institute
  • 2013 - Elected Member American Society for Clinical Investigation (ASCI)
  • 2015 - 2017 Neuroendocrine Tumor Award American Association for Cancer Research (AACR)
  • 2017 - Outstanding Mentor Award University of California San Francisco
  • 2018 - Stein Innovation Award Research to Prevent Blindness , Inc.
  • 2019 - Outstanding Investigator Award American Society for Investigative Pathology (ASIP)
Publications
  1. Oakes SA. Endoplasmic Reticulum Stress Signaling in Cancer Cells. Am J Pathol. 2020 05; 190(5):934-946. View in: PubMed

  2. Moore PC, Qi JY, Thamsen M, Ghosh R, Peng J, Gliedt MJ, Meza-Acevedo R, Warren RE, Hiniker A, Kim GE, Maly DJ, Backes BJ, Papa FR, Oakes SA. Parallel Signaling through IRE1a and PERK Regulates Pancreatic Neuroendocrine Tumor Growth and Survival. Cancer Res. 2019 12 15; 79(24):6190-6203. View in: PubMed

  3. Moore PC, Cortez JT, Chamberlain CE, Alba D, Berger AC, Quandt Z, Chan A, Cheng MH, Bautista JL, Peng J, German MS, Anderson MS, Oakes SA. Elastase 3B mutation links to familial pancreatitis with diabetes and pancreatic adenocarcinoma. J Clin Invest. 2019 08 01; 129(11):4676-4681. View in: PubMed

  4. Brondfield S, Boscardin C, Strewler G, Hyland K, Oakes SA, Nishimura H, Crawford J, Hauer KE. A Medical Student Inquiry Behavior Assessment Tool: Development and Validity Evidence. Acad Med. 2019 04; 94(4):586-594. View in: PubMed

  5. Hiniker A, Oakes SA, Rao RC. Bilateral Choroidal Metastases from Pancreatic Adenocarcinoma. Ophthalmology. 2017 12; 124(12):1825. View in: PubMed

  6. Moore PC, Oakes SA. CPEB4 links the clock and the UPR to protect the liver. Nat Cell Biol. 2017 01 31; 19(2):79-81. View in: PubMed

  7. Oakes SA. Endoplasmic reticulum proteostasis: a key checkpoint in cancer. Am J Physiol Cell Physiol. 2017 Feb 01; 312(2):C93-C102. View in: PubMed

  8. Wang ES, Reyes NA, Melton C, Huskey NE, Momcilovic O, Goga A, Blelloch R, Oakes SA. Fas-Activated Mitochondrial Apoptosis Culls Stalled Embryonic Stem Cells to Promote Differentiation. Curr Biol. 2015 Dec 07; 25(23):3110-8. View in: PubMed

  9. Hetz C, Chevet E, Oakes SA. Erratum: Proteostasis control by the unfolded protein response. Nat Cell Biol. 2015 Aug; 17(8):1088. View in: PubMed

  10. Hetz C, Chevet E, Oakes SA. Proteostasis control by the unfolded protein response. Nat Cell Biol. 2015 Jul; 17(7):829-38. View in: PubMed

  11. Huskey NE, Guo T, Evason KJ, Momcilovic O, Pardo D, Creasman KJ, Judson RL, Blelloch R, Oakes SA, Hebrok M, Goga A. 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. View in: PubMed

  12. Guo WT, Wang XW, Yan YL, Li YP, Yin X, Zhang Q, Melton C, Shenoy A, Reyes NA, Oakes SA, Blelloch R, Wang Y. 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. View in: PubMed

  13. Oakes SA, Papa FR. The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol. 2015; 10:173-94. View in: PubMed

  14. Crane CA, Austgen K, Haberthur K, Hofmann C, Moyes KW, Avanesyan L, Fong L, Campbell MJ, Cooper S, Oakes SA, Parsa AT, Lanier LL. 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 02; 111(35):12823-8. View in: PubMed

  15. Ghosh R, Wang L, Wang ES, Perera BG, Igbaria A, Morita S, Prado K, Thamsen M, Caswell D, Macias H, Weiberth KF, Gliedt MJ, Alavi MV, Hari SB, Mitra AK, Bhhatarai B, Schürer SC, Snapp EL, Gould DB, German MS, Backes BJ, Maly DJ, Oakes SA, Papa FR. Allosteric inhibition of the IRE1a RNase preserves cell viability and function during endoplasmic reticulum stress. Cell. 2014 Jul 31; 158(3):534-48. View in: PubMed

  16. van Dis V, Kuijpers M, Haasdijk ED, Teuling E, Oakes SA, Hoogenraad CC, Jaarsma D. Golgi fragmentation precedes neuromuscular denervation and is associated with endosome abnormalities in SOD1-ALS mouse motor neurons. Acta Neuropathol Commun. 2014 Apr 07; 2:38. View in: PubMed

  17. Wang L, Perera BG, Hari SB, Bhhatarai B, Backes BJ, Seeliger MA, Schürer SC, Oakes SA, Papa FR, Maly DJ. Divergent allosteric control of the IRE1a endoribonuclease using kinase inhibitors. Nat Chem Biol. 2012 Dec; 8(12):982-9. View in: PubMed

  18. Upton JP, Wang L, Han D, Wang ES, Huskey NE, Lim L, Truitt M, McManus MT, Ruggero D, Goga A, Papa FR, Oakes SA. IRE1a cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science. 2012 Nov 09; 338(6108):818-22. View in: PubMed

  19. Lerner AG, Upton JP, Praveen PV, Ghosh R, Nakagawa Y, Igbaria A, Shen S, Nguyen V, Backes BJ, Heiman M, Heintz N, Greengard P, Hui S, Tang Q, Trusina A, Oakes SA, Papa FR. IRE1a induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab. 2012 Aug 08; 16(2):250-64. View in: PubMed

  20. Cheng CK, Gustafson WC, Charron E, Houseman BT, Zunder E, Goga A, Gray NS, Pollok B, Oakes SA, James CD, Shokat KM, Weiss WA, Fan QW. 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. View in: PubMed

  21. Austgen K, Johnson ET, Park TJ, Curran T, Oakes SA. The adaptor protein CRK is a pro-apoptotic transducer of endoplasmic reticulum stress. Nat Cell Biol. 2011 Dec 18; 14(1):87-92. View in: PubMed

  22. Austgen K, Oakes SA, Ganem D. Multiple defects, including premature apoptosis, prevent Kaposi's sarcoma-associated herpesvirus replication in murine cells. J Virol. 2012 Feb; 86(3):1877-82. View in: PubMed

  23. Shore GC, Papa FR, Oakes SA. Signaling cell death from the endoplasmic reticulum stress response. Curr Opin Cell Biol. 2011 Apr; 23(2):143-9. View in: PubMed

  24. Fan QW, Cheng C, Hackett C, Feldman M, Houseman BT, Nicolaides T, Haas-Kogan D, James CD, Oakes SA, Debnath J, Shokat KM, Weiss WA. Akt and autophagy cooperate to promote survival of drug-resistant glioma. Sci Signal. 2010 Nov 09; 3(147):ra81. View in: PubMed

  25. Reyes NA, Fisher JK, Austgen K, VandenBerg S, Huang EJ, Oakes SA. 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. View in: PubMed

  26. Han D, Lerner AG, Vande Walle L, Upton JP, Xu W, Hagen A, Backes BJ, Oakes SA, Papa FR. IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell. 2009 Aug 07; 138(3):562-75. View in: PubMed

  27. Upton JP, Austgen K, Nishino M, Coakley KM, Hagen A, Han D, Papa FR, Oakes SA. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol Cell Biol. 2008 Jun; 28(12):3943-51. View in: PubMed

  28. Han D, Upton JP, Hagen A, Callahan J, Oakes SA, Papa FR. A kinase inhibitor activates the IRE1alpha RNase to confer cytoprotection against ER stress. Biochem Biophys Res Commun. 2008 Jan 25; 365(4):777-83. View in: PubMed

  29. Oakes SA. Mitochondria control calcium entry at the immunological synapse. Proc Natl Acad Sci U S A. 2007 Sep 25; 104(39):15171-2. View in: PubMed

  30. Oakes SA, Lin SS, Bassik MC. The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins. Curr Mol Med. 2006 Feb; 6(1):99-109. View in: PubMed

  31. Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T, Korsmeyer SJ. Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci U S A. 2005 Jan 04; 102(1):105-10. View in: PubMed

  32. Oakes SA, Korsmeyer SJ. Untangling the web: mitochondrial fission and apoptosis. Dev Cell. 2004 Oct; 7(4):460-2. View in: PubMed

  33. Bassik MC, Scorrano L, Oakes SA, Pozzan T, Korsmeyer SJ. Phosphorylation of BCL-2 regulates ER Ca2+ homeostasis and apoptosis. EMBO J. 2004 Mar 10; 23(5):1207-16. View in: PubMed

  34. Oakes SA, Opferman JT, Pozzan T, Korsmeyer SJ, Scorrano L. Regulation of endoplasmic reticulum Ca2+ dynamics by proapoptotic BCL-2 family members. Biochem Pharmacol. 2003 Oct 15; 66(8):1335-40. View in: PubMed

  35. Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, Korsmeyer SJ. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science. 2003 Apr 04; 300(5616):135-9. View in: PubMed

  36. Scorrano L, Ashiya M, Buttle K, Weiler S, Oakes SA, Mannella CA, Korsmeyer SJ. A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev Cell. 2002 Jan; 2(1):55-67. View in: PubMed

  37. Candotti F, Oakes SA, Johnston JA, Giliani S, Schumacher RF, Mella P, Fiorini M, Ugazio AG, Badolato R, Notarangelo LD, Bozzi F, Macchi P, Strina D, Vezzoni P, Blaese RM, O'Shea JJ, Villa A. Structural and functional basis for JAK3-deficient severe combined immunodeficiency. Blood. 1997 Nov 15; 90(10):3996-4003. View in: PubMed

  38. Taylor N, Candotti F, Smith S, Oakes SA, Jahn T, Isakov J, Puck JM, O'Shea JJ, Weinberg K, Johnston JA. Interleukin-4 signaling in B lymphocytes from patients with X-linked severe combined immunodeficiency. J Biol Chem. 1997 Mar 14; 272(11):7314-9. View in: PubMed

  39. Oakes SA, Candotti F, Johnston JA, Chen YQ, Ryan JJ, Taylor N, Liu X, Hennighausen L, Notarangelo LD, Paul WE, Blaese RM, O'Shea JJ. Signaling via IL-2 and IL-4 in JAK3-deficient severe combined immunodeficiency lymphocytes: JAK3-dependent and independent pathways. Immunity. 1996 Dec; 5(6):605-15. View in: PubMed

  40. Candotti F, Oakes SA, Johnston JA, Notarangelo LD, O'Shea JJ, Blaese RM. In vitro correction of JAK3-deficient severe combined immunodeficiency by retroviral-mediated gene transduction. J Exp Med. 1996 Jun 01; 183(6):2687-92. View in: PubMed

  41. Johnston JA, Wang LM, Hanson EP, Sun XJ, White MF, Oakes SA, Pierce JH, O'Shea JJ. Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases. J Biol Chem. 1995 Dec 01; 270(48):28527-30. View in: PubMed