Rushika Perera, PhD

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
Rushika Perera, PhD

Assistant Professor, Department of Anatomy, UCSF

rushika.perera@ucsf.edu

Box 0452, UCSF
San Francisco, CA 94143

UCSF Profiles

Cancer Center Membership

Member » Non-aligned

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
  • 2017-2018
    Damon Rynyon-Rachleff Innovation Award

Selected Publications

  1. Perera RM, Zoncu R. The Lysosome as a Regulatory Hub. Annu Rev Cell Dev Biol. 2016 Aug 3.
    View on PubMed
  2. 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
  3. 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
  4. 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 10.
    View on PubMed
  5. 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
  6. 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.
    View on PubMed
  7. 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 4; 496(7443):101-5.
    View on PubMed
  8. 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
  9. Perera RM, Bardeesy N. On oncogenes and tumor suppressor genes in the mammary gland. Cold Spring Harb Perspect Biol. 2012 Jun; 4(6).
    View on PubMed
  10. Perera RM, Bardeesy N. Cancer: when antioxidants are bad. Nature. 2011 Jul 7; 475(7354):43-4.
    View on PubMed
  11. 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 9; 190(3):307-15.
    View on PubMed
  12. 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
  13. Zoncu R, Perera RM, Balkin DM, Pirruccello M, Toomre D, De Camilli P. A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes. Cell. 2009 Mar 20; 136(6):1110-21.
    View on PubMed
  14. Frost A, Perera R, Roux A, Spasov K, Destaing O, Egelman EH, De Camilli P, Unger VM. Structural basis of membrane invagination by F-BAR domains. Cell. 2008 Mar 7; 132(5):807-17.
    View on PubMed
  15. Perera RM, Zoncu R, Johns TG, Pypaert M, Lee FT, Mellman I, Old LJ, Toomre DK, Scott AM. Internalization, intracellular trafficking, and biodistribution of monoclonal antibody 806: a novel anti-epidermal growth factor receptor antibody. Neoplasia. 2007 Dec; 9(12):1099-110.
    View on PubMed
  16. Johns TG, Perera RM, Vernes SC, Vitali AA, Cao DX, Cavenee WK, Scott AM, Furnari FB. The efficacy of epidermal growth factor receptor-specific antibodies against glioma xenografts is influenced by receptor levels, activation status, and heterodimerization. Clin Cancer Res. 2007 Mar 15; 13(6):1911-25.
    View on PubMed
  17. Zoncu R, Perera RM, Sebastian R, Nakatsu F, Chen H, Balla T, Ayala G, Toomre D, De Camilli PV. Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate. Proc Natl Acad Sci U S A. 2007 Mar 6; 104(10):3793-8.
    View on PubMed
  18. Perera RM, Zoncu R, Lucast L, De Camilli P, Toomre D. Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages. Proc Natl Acad Sci U S A. 2006 Dec 19; 103(51):19332-7.
    View on PubMed
  19. Perera RM, Narita Y, Furnari FB, Gan HK, Murone C, Ahlkvist M, Luwor RB, Burgess AW, Stockert E, Jungbluth AA, Old LJ, Cavenee WK, Scott AM, Johns TG. Treatment of human tumor xenografts with monoclonal antibody 806 in combination with a prototypical epidermal growth factor receptor-specific antibody generates enhanced antitumor activity. Clin Cancer Res. 2005 Sep 1; 11(17):6390-9.
    View on PubMed
  20. Luwor RB, Zhu HJ, Walker F, Vitali AA, Perera RM, Burgess AW, Scott AM, Johns TG. The tumor-specific de2-7 epidermal growth factor receptor (EGFR) promotes cells survival and heterodimerizes with the wild-type EGFR. Oncogene. 2004 Aug 12; 23(36):6095-104.
    View on PubMed

Go to UCSF Profiles, powered by CTSI