Research Summary

I am an Associate 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

  • April 1, 2021 - March 31, 2026 - Dissecting new mechanisms of lysosome quality control in health and disease , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA260249
  • April 1, 2021 - March 31, 2026 - Targeting the autophagy-lysosome system to block pancreatic cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA251726
  • September 3, 2020 - May 31, 2025 - Identifying Molecular Drivers of Cellular Plasticity in Pancreatic Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA240603
  • September 30, 2016 - May 31, 2021 - Tracking tumor evolution through in vivo organelle profiling , Principal Investigator . Sponsor: NIH, 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

  • 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
  • 2021
    Gunter Blobel Early Career Award recipient, American Society for Cell Biology
  • 2022-2024
    AACR-MPM Oncology Charitable Foundation Transformative Cancer Research Grant

Selected Publications

  1. Lui I, Schaefer K, Kirkemo LL, Zhou J, Perera RM, Leung KK, Wells JA. Hypoxia Induces Extensive Protein and Proteolytic Remodeling of the Cell Surface in Pancreatic Adenocarcinoma (PDAC) Cell Lines. J Proteome Res. 2025 May 01.  View on PubMed
  2. Jain A, Heremans I, Rademaker G, Detomasi TC, Rohweder P, Anderson D, Zhang J, Hernandez GA, Gupta S, von Linde T, Lange M, Spacci M, Luo J, Citron YR, Olzmann JA, Dawson DW, Craik CS, Bommer G, Perera RM, Zoncu R. Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins. Science. 2025 Mar 28; 387(6741):eadq8331.  View on PubMed
  3. Kovalski JR, Sarioglu G, Subramanyam V, Hernandez G, Rademaker G, Oses-Prieto JA, Slota M, Mohan N, Yiakis K, Liu I, Wen KW, Kim GE, Miglani S, Burlingame AL, Goodarzi H, Perera RM, Ruggero D. Functional screen identifies RBM42 as a mediator of oncogenic mRNA translation specificity. Nat Cell Biol. 2025 Mar; 27(3):518-529.  View on PubMed
  4. Jain A, Heremans I, Rademaker G, Detomasi TC, Hernandez GA, Zhang J, Gupta S, von Linde T, Lange M, Spacci M, Rohweder P, Anderson D, Citron YR, Olzmann JA, Dawson DW, Craik CS, Bommer G, Perera RM, Zoncu R. Leucine Aminopeptidase LyLAP enables lysosomal degradation of membrane proteins. bioRxiv. 2024 Dec 14.  View on PubMed
  5. Berquez M, Li AL, Luy MA, Venida AC, O'Loughlin T, Rademaker G, Barpanda A, Hu J, Yano J, Wiita A, Gilbert LA, Bruno PM, Perera RM. A multi-subunit autophagic capture complex facilitates degradation of ER stalled MHC-I in pancreatic cancer. bioRxiv. 2024 Oct 29.  View on PubMed
  6. Kovalski JR, Sarioglu G, Subramanyam V, Hernandez G, Rademaker G, Oses-Prieto JA, Slota M, Mohan N, Yiakis K, Liu I, Wen KW, Kim GE, Miglani S, Burlingame AL, Goodarzi H, Perera RM, Ruggero D. Functional screen for mediators of onco-mRNA translation specificity. bioRxiv. 2024 Oct 11.  View on PubMed
  7. Paul S. Soma, Rushika Perera. Metabolomics Tools in Antiviral Research. Advances in Antiviral Research. 2024 May 3; 123-146.  View on PubMed
  8. Ali L. Brehm, Tillie J. Dunham, Samantha M. Pinto, Kaitlynn A. Williams, Kathryn L. Coffin, Molly E. Ring, Oshani C. Ratnayake, Joel Rovnak, Rushika Perera. The 23rd Annual Meeting of the Rocky Mountain Virology Association. Viruses. 2024 Apr 10; 16(4):586.  View on PubMed
  9. Settembre C, Perera RM. Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology. Nat Rev Mol Cell Biol. 2024 Mar; 25(3):223-245.  View on PubMed
  10. Yang X, Wen J, Yang H, Jones IR, Zhu X, Liu W, Li B, Clelland CD, Luo W, Wong MY, Ren X, Cui X, Song M, Liu H, Chen C, Eng N, Ravichandran M, Sun Y, Lee D, Van Buren E, Jiang MZ, Chan CSY, Ye CJ, Perera RM, Gan L, Li Y, Shen Y. Functional characterization of Alzheimer's disease genetic variants in microglia. Nat Genet. 2023 Oct; 55(10):1735-1744.  View on PubMed
  11. Zoncu R, Perera RM. Emerging roles of the MiT/TFE factors in cancer. Trends Cancer. 2023 10; 9(10):817-827.  View on PubMed
  12. Ravichandran M, Hu J, Cai C, Ward NP, Venida A, Foakes C, Kuljanin M, Yang A, Hennessey CJ, Yang Y, Desousa BR, Rademaker G, Staes AAL, Cakir Z, Jain IH, Aguirre AJ, Mancias JD, Shen Y, DeNicola GM, Perera RM. Coordinated Transcriptional and Catabolic Programs Support Iron-Dependent Adaptation to RAS-MAPK Pathway Inhibition in Pancreatic Cancer. Cancer Discov. 2022 09 02; 12(9):2198-2219.  View on PubMed
  13. Shin HR, Citron YR, Wang L, Tribouillard L, Goul CS, Stipp R, Sugasawa Y, Jain A, Samson N, Lim CY, Davis OB, Castaneda-Carpio D, Qian M, Nomura DK, Perera RM, Park E, Covey DF, Laplante M, Evers AS, Zoncu R. Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1. Science. 2022 09 16; 377(6612):1290-1298.  View on PubMed
  14. Hernandez GA, Perera RM. Autophagy in cancer cell remodeling and quality control. Mol Cell. 2022 04 21; 82(8):1514-1527.  View on PubMed
  15. Zoncu R, Perera RM. Built to last: lysosome remodeling and repair in health and disease. Trends Cell Biol. 2022 07; 32(7):597-610.  View on PubMed
  16. Akkari L, Finley SD, Ho PC, Jenkins M, Maier BB, McGranahan N, Mutebi M, Perera RM, Robles-Espinoza CD, Vardhana S, Wan L, Xu MM. Challenges and opportunities in 2021. Nat Cancer. 2021 12; 2(12):1278-1283.  View on PubMed
  17. Perera RM. Zooming in on the cell biology of disease. Mol Biol Cell. 2021 12 01; 32(22):ae4.  View on PubMed
  18. 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 10 01; 40(19):e108863.  View on PubMed
  19. 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 07 12; 56(13):1989-2006.e6.  View on PubMed
  20. Burke JM, St Clair LA, Perera R, Parker R. Rapid decay of host basal mRNAs during SARS-CoV-2 infection perturbs host antiviral mRNA biogenesis and export. bioRxiv. 2021 Apr 19.  View on PubMed

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