Research Summary

Our research has expanded the traditional lines of investigation into cancer biology, uncovering a novel layer of control to gene regulation for cancer initiation at the post-genomic level. We have been at the forefront of realizing that the cancer proteome is profoundly shaped by molecular events downstream of transcription. In particular, across evolution, many host-parasite relationships usurp the translation machinery to drive a tailored protein synthesis program. For example, viruses hijack the host's translation apparatus as a means to drive the selective translation of their own viral mRNAs. Similarly, our research has been fundamental in establishing that cancer cells have usurped the cell's translation machinery. This provides a unique means for production of tailored proteins that selectively fuel cancer cell growth, proliferation and metastasis. Utilizing biochemical, molecular, and genetic approaches within the context of unique animal models, we are uncovering new mechanisms for gene-specific control of mRNA translation vital for cancer initiation. These results have been instrumental in the design of a new generation of compounds that modulate protein synthesis and act as novel therapeutic agents. Presently, there is an unprecedented potential for changing the landscape of cancer therapies with the first targeted molecules for oncogenic-dependent protein synthesis. This reflects a new cancer cell vulnerability that may pave a new, fundamental shift in targeting oncogenic pathways that is less likely to trigger drug resistance.

Research Funding

  • August 6, 2019 - July 31, 2026 - Mechanisms of regulated translation control in cancer and its therapeutic implications , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R35CA242986
  • September 1, 2011 - June 30, 2022 - Deciphering the role of the translational oncogenic program in Prostate Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA154916
  • May 1, 2014 - April 30, 2020 - elF4E-Dependent Translation Control in the Oncogenic Stress Response and Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA184624
  • July 1, 2009 - April 30, 2020 - Delineating the Mechanisms Responsible for Synthetic Lethality in MYC-induced Tumorigenesis Driven by Control of Protein Synthesis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA140456
  • September 1, 2014 - June 30, 2019 - MYCN, mTOR and translation control in medulloblastoma , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01NS089868
  • August 1, 2014 - April 30, 2019 - X-linked Dyskeratosis Congenita and ribosomal frameshifting , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01HL119439
  • August 1, 2006 - June 30, 2017 - Role of ribosome impairments in X-linked Dyskeratosis Congenita pathogenesis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DK098057
  • March 1, 1982 - May 31, 2015 - Bio-Organic Biomedical Mass Spectrometry Resource , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P41RR001614
  • August 1, 2006 - June 30, 2011 - Role of rRNA Modifications in Dyskeratosis Congenita and Translation Control , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01HL085572

Education

University of Rome, La Sapienza, Italy, BS, magna cum laude, Molecular & Cellular Biology, 1994
University of Rome, La Sapienza, Italy, PhD, magna cum laude, Molecular & Cellular Biology, 1998

Honors & Awards

  • 1994
    Enichem Society fellowship
  • 1998-2000
    American-Italian Cancer Foundation fellowship
  • 2003
    Outstanding Research Fellow Award, Memorial Sloan Kettering Cancer Center
  • 2005
    V Foundation Scholar Grant
  • 2006
    Commonwealth Universal Research Enhancement Program Award, Pennsylvania Department of Health
  • 2008
    Gertrude B. Elion Award, American Association for Cancer Research
  • 2010
    Leukemia & Lymphoma Society Scholar Award
  • 2010
    UCSF Program for Breakthrough Biomedical Research Integrative Award
  • 2011
    Helen Diller Family Endowed Chair of Basic Science in Urologic Cancer
  • 2019
    American Cancer Society Research Professor
  • 2019
    Outstanding Investigator Award (R35), National Cancer Institute

Selected Publications

  1. Kovalski JR, Ruggero D. Breaking up translation condensates in cancer. Nat Cell Biol. 2025 Apr; 27(4):558-560.  View on PubMed
  2. Kuzuoglu-Ozturk D, Nguyen HG, Xue L, Figueredo E, Subramanyam V, Liu I, Bonitto K, Noronha A, Dabrowska A, Cowan JE, Oses-Prieto JA, Burlingame AL, Worland ST, Carroll PR, Ruggero D. Small-molecule RNA therapeutics to target prostate cancer. Cancer Cell. 2025 May 12; 43(5):841-855.e8.  View on PubMed
  3. Chesner LN, Polesso F, Graff JN, Hawley JE, Smith AK, Lundberg A, Das R, Shenoy T, Sjöström M, Zhao F, Hu YM, Linder S, Chen WS, Hawkins RM, Shrestha R, Zhu X, Foye A, Li H, Kim LM, Bhalla M, O'loughlin T, Kuzuoglu-Ozturk D, Hua JT, Badura ML, Wilkinson S, Trostel SY, Bergman AM, Ruggero D, Drake CG, Sowalsky AG, Fong L, Cooperberg MR, Zwart W, Guan X, Ashworth A, Xia Z, Quigley DA, Gilbert LA, Feng FY, Moran AE. Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer. Cancer Discov. 2025 Mar 03; 15(3):481-494.  View on PubMed
  4. 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
  5. 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
  6. Joanna R Kovalski, Goksu Sarioglu, Vishvak Subramanyam, Grace Hernandez, Gilles Rademaker, Juan A Oses-Prieto, Macey Slota, Kwun Wah Wen, Grace E Kim, Alma L Burlingame, Hani Goodarzi, Rushika M Perera, Davide Ruggero. Abstract A078: Functional screen for mediators of onco-mRNA translation specificity in pancreatic cancer. Cancer Research. 2024 Sep 15; 84(17_Supplement_2):a078-a078.  View on PubMed
  7. Susanto TT, Hung V, Levine AG, Chen Y, Kerr CH, Yoo Y, Oses-Prieto JA, Fromm L, Zhang Z, Lantz TC, Fujii K, Wernig M, Burlingame AL, Ruggero D, Barna M. RAPIDASH: Tag-free enrichment of ribosome-associated proteins reveals composition dynamics in embryonic tissue, cancer cells, and macrophages. Mol Cell. 2024 Sep 19; 84(18):3545-3563.e25.  View on PubMed
  8. Biffo S, Ruggero D, Santoro MM. The crosstalk between metabolism and translation. Cell Metab. 2024 Sep 03; 36(9):1945-1962.  View on PubMed
  9. Dabrowska A, Ruggero D. snoRNAs in making "snoman" ribosomes. Mol Cell. 2024 Aug 22; 84(16):3008-3010.  View on PubMed
  10. Yang H, Zingaro VA, Lincoff J, Tom H, Oikawa S, Oses-Prieto JA, Edmondson Q, Seiple I, Shah H, Kajimura S, Burlingame AL, Grabe M, Ruggero D. Remodelling of the translatome controls diet and its impact on tumorigenesis. Nature. 2024 Sep; 633(8028):189-197.  View on PubMed
  11. Dey N, Koumenis C, Ruggero D, Fuchs SY, Diehl JA. miR-217 Regulates Normal and Tumor Cell Fate Following Induction of Endoplasmic Reticulum Stress. Mol Cancer Res. 2024 04 02; 22(4):360-372.  View on PubMed
  12. Susanto TT, Hung V, Levine AG, Kerr CH, Yoo Y, Chen Y, Oses-Prieto JA, Fromm L, Fujii K, Wernig M, Burlingame AL, Ruggero D, Barna M. RAPIDASH: A tag-free enrichment of ribosome-associated proteins reveals compositional dynamics in embryonic tissues and stimulated macrophages. bioRxiv. 2023 Dec 07.  View on PubMed
  13. Macaya I, Roman M, Welch C, Entrialgo-Cadierno R, Salmon M, Santos A, Feliu I, Kovalski J, Lopez I, Rodriguez-Remirez M, Palomino-Echeverria S, Lonfgren SM, Ferrero M, Calabuig S, Ludwig IA, Lara-Astiaso D, Jantus-Lewintre E, Guruceaga E, Narayanan S, Ponz-Sarvise M, Pineda-Lucena A, Lecanda F, Ruggero D, Khatri P, Santamaria E, Fernandez-Irigoyen J, Ferrer I, Paz-Ares L, Drosten M, Barbacid M, Gil-Bazo I, Vicent S. Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer. Nat Commun. 2023 10 10; 14(1):6332.  View on PubMed
  14. Zhulyn O, Rosenblatt HD, Shokat L, Dai S, Kuzuoglu-Öztürk D, Zhang Z, Ruggero D, Shokat KM, Barna M. Evolutionarily divergent mTOR remodels translatome for tissue regeneration. Nature. 2023 Aug; 620(7972):163-171.  View on PubMed
  15. Xu AF, Molinuevo R, Fazzari E, Tom H, Zhang Z, Menendez J, Casey KM, Ruggero D, Hinck L, Pritchard JK, Barna M. Subfunctionalized expression drives evolutionary retention of ribosomal protein paralogs Rps27 and Rps27l in vertebrates. Elife. 2023 Jun 12; 12.  View on PubMed
  16. Kuzuoglu-Ozturk D, Aksoy O, Schmidt C, Lea R, Larson JD, Phelps RRL, Nasholm N, Holt M, Contreras A, Huang M, Wong-Michalak S, Shao H, Wechsler-Reya R, Phillips JJ, Gestwicki JE, Ruggero D, Weiss WA. N-myc-Mediated Translation Control Is a Therapeutic Vulnerability in Medulloblastoma. Cancer Res. 2023 01 04; 83(1):130-140.  View on PubMed
  17. Forester CM, Oses-Prieto JA, Phillips NJ, Miglani S, Pang X, Byeon GW, DeMarco R, Burlingame A, Barna M, Ruggero D. Regulation of eIF4E guides a unique translational program to control erythroid maturation. Sci Adv. 2022 Dec 23; 8(51):eadd3942.  View on PubMed
  18. Wang HY, Yang H, Holm M, Tom H, Oltion K, Al-Khdhairawi AAQ, Weber JF, Blanchard SC, Ruggero D, Taunton J. Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumour eEF1A antagonist SR-A3. Nat Chem. 2022 12; 14(12):1443-1450.  View on PubMed
  19. Xu Y, Ruggero D. A tRF nucleator for Nucleolin in cancer metastasis. Mol Cell. 2022 07 21; 82(14):2536-2538.  View on PubMed
  20. Barna M, Karbstein K, Tollervey D, Ruggero D, Brar G, Greer EL, Dinman JD. The promises and pitfalls of specialized ribosomes. Mol Cell. 2022 06 16; 82(12):2179-2184.  View on PubMed

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