University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Rushika Perera, PhD

Rushika Perera, PhD

Assistant Professor, Department of Anatomy, UCSF

Cancer Center Program Memberships

Cancer Immunology

Research Summary

Pancreatic ductal adenocarcinoma (PDA) is characterized by hypoxia and limited nutrient availability, and exhibits activated autophagy (cellular self-catabolism) as a necessary adaptive metabolic change. How this pathway is activated and regulated in PDA was unknown. My studies identified the MiT/TFE proteins as master regulators of autophagy and lysosome biogenesis in PDA. These proteins function through constitutive nuclear import via binding to novel interacting partners thus mediating constitutive transcriptional activation of a coordinate set of autophagy and lysosome genes. Regulation of this gene program by the MiT/TFE proteins is essential for the proper functioning of an entire organelle system and is required for maintaining metabolic homeostasis in PDA. The goal of this proposal is to determine the precise metabolic output of the increased catabolic function of lysosomes in PDA as a means to determine how the cell gauges and adapts to fluctuations in internal and external nutrient availability. Through a combination of in vitro reconstitution assays coupled with utilization of primary patient derived PDA cultures, established human PDA cell lines and mouse tumor models we will address the importance and cancer specific function of lysosomes in driving PDA growth in nutrient poor microenvironments as well as address the remarkable resilience of this malignancy to a variety of anti-cancer therapies. In addition my proposed studies aim to identify unique metabolic dependencies of PDA that would inform the development of novel therapeutic strategies for treatment of pancreatic cancer and other aggressive malignancies. These studies form the foundation of my long-term research program dedicated to understanding the mechanisms of organelle function and metabolic reprogramming and their contribution to cancer growth.

Education

University of Melbourne, Australia, BSc, 1999, Pathology/ Biochemistry
University of Melbourne and Ludwig Institute for Cancer Research, BSc, 2000, Cancer Biology
University of Melbourne and Ludwig Institute for Cancer Research, PhD, 2007, Cancer Biology
Yale University, postdoctoral, 2008, Cell Biology
MGH Cancer Center, postdoctoral, 2013, Cancer Biology
MGH Cancer Center, Instructor, 2015, Cancer Biology


Professional Experience

  • 2001-2007
    Graduate Research, University of Melbourne, Ludwig Institute for Cancer Research
  • 2005-2008
    Postdoctoral Fellow, Yale University
  • 2008-2013
    Postdoctoral Fellow, Massachusetts General Hospital / Harvard Medical School
  • 2013-2015
    Instructor in Medicine (Harvard Medical School) and Assistant in Genetics (MGH)
  • 2015-present
    Assistant Professor, Department of Anatomy, UCSF

Honors & Awards

  • 2001
    John and Allan Gilmour Award, The University of Melbourne, Australia
  • 2001
    RJ Fletcher Award, The University of Melbourne, Australia
  • 2002-2004
    Melbourne Research Scholarship, The University of Melbourne, Australia
  • 2005
    Student commendation for outstanding achievement during PhD, (money prize)
  • 2010-2011
    ECOR Fund for Medical Discovery Fellowship, MGH Cancer Center
  • 2011-2012
    Dana Faber Cancer Institute/HCC GI SPORE Career Development Award
  • 2014
    Office for Research Career Development, MGH – Research Fellow Award
  • 2014-2015
    Andrew L. Warshaw Institute for Pancreatic Cancer Research Fellow Award
  • 2015
    American Association for Cancer Research NextGen STAR
  • 2014-2016
    Hirshberg Foundation for Pancreatic Cancer Seed Grant Recipient
  • 2016-2018
    AACR-Pancreatic Cancer Action Network Career Development Award
  • 2016-2021
    NIH Director’s New Innovator Award
  • 2016-2020
    Damon Runyon-Rachleff Innovation Award

Selected Publications

  1. Espinosa DA, Beatty PR, Puerta-Guardo H, Islam MN, Belisle JT, Perera R, Harris E. Increased serum sialic acid is associated with morbidity and mortality in a murine model of dengue disease. J Gen Virol. 2019 Sep 17.
    View on PubMed
  2. Adams CR, Htwe HH, Marsh T, Wang AL, Montoya ML, Subbaraj L, Tward AD, Bardeesy N, Perera RM. Transcriptional control of subtype switching ensures adaptation and growth of pancreatic cancer. Elife. 2019 05 28; 8.
    View on PubMed
  3. Venida A, Perera RM. Host Control of Tumor Feeding: Autophagy Holds the Key. Cell Metab. 2019 Feb 05; 29(2):236-238.
    View on PubMed
  4. Perera RM, Di Malta C, Ballabio A. MiT/TFE Family of Transcription Factors, Lysosomes, and Cancer. Annu Rev Cancer Biol. 2019 03; 3:203-222.
    View on PubMed
  5. Stabell AC, Meyerson NR, Gullberg RC, Gilchrist AR, Webb KJ, Old WM, Perera R, Sawyer SL. Dengue viruses cleave STING in humans but not in nonhuman primates, their presumed natural reservoir. Elife. 2018 03 20; 7.
    View on PubMed
  6. Di Malta C, Siciliano D, Calcagni A, Monfregola J, Punzi S, Pastore N, Eastes AN, Davis O, De Cegli R, Zampelli A, Di Giovannantonio LG, Nusco E, Platt N, Guida A, Ogmundsdottir MH, Lanfrancone L, Perera RM, Zoncu R, Pelicci PG, Settembre C, Ballabio A. Transcriptional activation of RagD GTPase controls mTORC1 and promotes cancer growth. Science. 2017 06 16; 356(6343):1188-1192.
    View on PubMed
  7. Castellano BM, Thelen AM, Moldavski O, Feltes M, van der Welle RE, Mydock-McGrane L, Jiang X, van Eijkeren RJ, Davis OB, Louie SM, Perera RM, Covey DF, Nomura DK, Ory DS, Zoncu R. Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-Pick C1 signaling complex. Science. 2017 03 24; 355(6331):1306-1311.
    View on PubMed
  8. Altshuler-Keylin S, Shinoda K, Hasegawa Y, Ikeda K, Hong H, Kang Q, Yang Y, Perera RM, Debnath J, Kajimura S. Beige Adipocyte Maintenance Is Regulated by Autophagy-Induced Mitochondrial Clearance. Cell Metab. 2016 09 13; 24(3):402-419.
    View on PubMed
  9. Perera RM, Zoncu R. The Lysosome as a Regulatory Hub. Annu Rev Cell Dev Biol. 2016 10 06; 32:223-253.
    View on PubMed
  10. Perera RM, Bardeesy N. Pancreatic Cancer Metabolism: Breaking It Down to Build It Back Up. Cancer Discov. 2015 Dec; 5(12):1247-61.
    View on PubMed
  11. Perera RM, Stoykova S, Nicolay BN, Ross KN, Fitamant J, Boukhali M, Lengrand J, Deshpande V, Selig MK, Ferrone CR, Settleman J, Stephanopoulos G, Dyson NJ, Zoncu R, Ramaswamy S, Haas W, Bardeesy N. Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism. Nature. 2015 Aug 20; 524(7565):361-5.
    View on PubMed
  12. Fitamant J, Kottakis F, Benhamouche S, Tian HS, Chuvin N, Parachoniak CA, Nagle JM, Perera RM, Lapouge M, Deshpande V, Zhu AX, Lai A, Min B, Hoshida Y, Avruch J, Sia D, Campreciós G, McClatchey AI, Llovet JM, Morrissey D, Raj L, Bardeesy N. YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression. Cell Rep. 2015 Mar 17; 10(10):1692-1707.
    View on PubMed
  13. Lee JJ, Perera RM, Wang H, Wu DC, Liu XS, Han S, Fitamant J, Jones PD, Ghanta KS, Kawano S, Nagle JM, Deshpande V, Boucher Y, Kato T, Chen JK, Willmann JK, Bardeesy N, Beachy PA. Stromal response to Hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci U S A. 2014 Jul 29; 111(30):E3091-100.
    View on PubMed
  14. Heilmann AM, Perera RM, Ecker V, Nicolay BN, Bardeesy N, Benes CH, Dyson NJ. CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. Cancer Res. 2014 Jul 15; 74(14):3947-58.
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  15. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, Kang Y, Fleming JB, Bardeesy N, Asara JM, Haigis MC, DePinho RA, Cantley LC, Kimmelman AC. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature. 2013 Apr 04; 496(7443):101-5.
    View on PubMed
  16. Perera RM, Bardeesy N. Ready, set, go: the EGF receptor at the pancreatic cancer starting line. Cancer Cell. 2012 Sep 11; 22(3):281-2.
    View on PubMed
  17. Perera RM, Bardeesy N. On oncogenes and tumor suppressor genes in the mammary gland. Cold Spring Harb Perspect Biol. 2012 Jun 01; 4(6).
    View on PubMed
  18. Perera RM, Bardeesy N. Cancer: when antioxidants are bad. Nature. 2011 Jul 06; 475(7354):43-4.
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  19. Nakatsu F, Perera RM, Lucast L, Zoncu R, Domin J, Gertler FB, Toomre D, De Camilli P. The inositol 5-phosphatase SHIP2 regulates endocytic clathrin-coated pit dynamics. J Cell Biol. 2010 Aug 09; 190(3):307-15.
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  20. Rothenberg SM, Mohapatra G, Rivera MN, Winokur D, Greninger P, Nitta M, Sadow PM, Sooriyakumar G, Brannigan BW, Ulman MJ, Perera RM, Wang R, Tam A, Ma XJ, Erlander M, Sgroi DC, Rocco JW, Lingen MW, Cohen EE, Louis DN, Settleman J, Haber DA. A genome-wide screen for microdeletions reveals disruption of polarity complex genes in diverse human cancers. Cancer Res. 2010 Mar 15; 70(6):2158-64.
    View on PubMed

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