Research Summary

I am an Assistant Professor in the Department of Anatomy, with appointments also in the Department of Pathology and the Helen Diller Family Comprehensive Cancer Center. My laboratory focuses on understanding how scavenging pathways such as autophagy and the lysosome - a degradative organelle - enables metabolic and cellular adaptation to stress and contributes to aggressive features of disease. Beyond mediating degradation of diverse macromolecules, the lysosome also plays an important role in signal transduction, cellular quality control, metabolism and detoxification.

My lab has a particular interest in how the lysosome contributes to cancer pathogenesis with a focus on studying pancreatic ductal adenocarcinoma (PDA). our work has identified novel mechanisms mediating constitutive activation of lysosome biogenesis via coordinated transcriptional upregulation of lysosome transcriptional signatures in PDA and in normal physiological contexts. We have also discovered a new role for autophagy and the lysosome in facilitating immune evasion of PDA cells through selective capture and degradation of Major Histocompatibility Complex Class I (MHC-I). Our ongoing research leverages our combined experience in cellular trafficking, autophagy and lysosome function combined with in vitro and in vivo model systems, organelle isolation and mass spectrometry based proteomics to determine critical roles of the lysosome in cancer progression and metastasis, tumor heterogeneity, stress adaptation and drug resistance.

Research Funding

  • September 30, 2016 - August 31, 2021 - Tracking tumor evolution through in vivo organelle profiling, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: DP2CA216364
  • September 30, 2016 - August 31, 2021 - Tracking tumor evolution through in vivo organelle profiling, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: DP2CA216364
  • September 30, 2016 - August 31, 2021 - Tracking tumor evolution through in vivo organelle profiling, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: DP2CA216364
  • September 30, 2016 - August 31, 2021 - Tracking tumor evolution through in vivo organelle profiling, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: DP2CA216364

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

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. Klionsky DJ, Petroni G, Amaravadi RK, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cadwell K, Cecconi F, Choi AMK, Choi ME, Chu CT, Codogno P, Colombo MI, Cuervo AM, Deretic V, Dikic I, Elazar Z, Eskelinen EL, Fimia GM, Gewirtz DA, Green DR, Hansen M, Jäättelä M, Johansen T, Juhász G, Karantza V, Kraft C, Kroemer G, Ktistakis NT, Kumar S, Lopez-Otin C, Macleod KF, Madeo F, Martinez J, Meléndez A, Mizushima N, Münz C, Penninger JM, Perera RM, Piacentini M, Reggiori F, Rubinsztein DC, Ryan KM, Sadoshima J, Santambrogio L, Scorrano L, Simon HU, Simon AK, Simonsen A, Stolz A, Tavernarakis N, Tooze SA, Yoshimori T, Yuan J, Yue Z, Zhong Q, Galluzzi L, Pietrocola F. Autophagy in major human diseases. EMBO J. 2021 Aug 30; e108863.  View on PubMed
  2. Kilinc S, Paisner R, Camarda R, Gupta S, Momcilovic O, Kohnz RA, Avsaroglu B, L'Etoile ND, Perera RM, Nomura DK, Goga A. Oncogene-regulated release of extracellular vesicles. Dev Cell. 2021 Jul 12; 56(13):1989-2006.e6.  View on PubMed
  3. Gupta S, Yano J, Mercier V, Htwe HH, Shin HR, Rademaker G, Cakir Z, Ituarte T, Wen KW, Kim GE, Zoncu R, Roux A, Dawson DW, Perera RM. Lysosomal retargeting of Myoferlin mitigates membrane stress to enable pancreatic cancer growth. Nat Cell Biol. 2021 03; 23(3):232-242.  View on PubMed
  4. Davis OB, Shin HR, Lim CY, Wu EY, Kukurugya M, Maher CF, Perera RM, Ordonez MP, Zoncu R. NPC1-mTORC1 Signaling Couples Cholesterol Sensing to Organelle Homeostasis and Is a Targetable Pathway in Niemann-Pick Type C. Dev Cell. 2021 02 08; 56(3):260-276.e7.  View on PubMed
  5. Yamamoto K, Venida A, Perera RM, Kimmelman AC. Selective autophagy of MHC-I promotes immune evasion of pancreatic cancer. Autophagy. 2020 08; 16(8):1524-1525.  View on PubMed
  6. Yamamoto K, Venida A, Yano J, Biancur DE, Kakiuchi M, Gupta S, Sohn ASW, Mukhopadhyay S, Lin EY, Parker SJ, Banh RS, Paulo JA, Wen KW, Debnath J, Kim GE, Mancias JD, Fearon DT, Perera RM, Kimmelman AC. Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature. 2020 05; 581(7806):100-105.  View on PubMed
  7. 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
  8. Venida A, Perera RM. Host Control of Tumor Feeding: Autophagy Holds the Key. Cell Metab. 2019 02 05; 29(2):236-238.  View on PubMed
  9. 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
  10. 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
  11. 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
  12. 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
  13. Perera RM, Zoncu R. The Lysosome as a Regulatory Hub. Annu Rev Cell Dev Biol. 2016 10 06; 32:223-253.  View on PubMed
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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

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