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

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. 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 Jul 26.  View on PubMed
  2. 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
  3. 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
  4. 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
  5. 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
  6. Xu Y, Ruggero D. A tRF nucleator for Nucleolin in cancer metastasis. Mol Cell. 2022 07 21; 82(14):2536-2538.  View on PubMed
  7. 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
  8. Liedmann S, Liu X, Guy CS, Crawford JC, Rodriguez DA, Kuzuoglu-Öztürk D, Guo A, Verbist KC, Temirov J, Chen MJ, Ruggero D, Zhang H, Thomas PG, Green DR. Localization of a TORC1-eIF4F translation complex during CD8+ T cell activation drives divergent cell fate. Mol Cell. 2022 07 07; 82(13):2401-2414.e9.  View on PubMed
  9. Kovalski JR, Kuzuoglu-Ozturk D, Ruggero D. Protein synthesis control in cancer: selectivity and therapeutic targeting. EMBO J. 2022 04 19; 41(8):e109823.  View on PubMed
  10. Xu Y, Huangyang P, Wang Y, Xue L, Devericks E, Nguyen HG, Yu X, Oses-Prieto JA, Burlingame AL, Miglani S, Goodarzi H, Ruggero D. ERα is an RNA-binding protein sustaining tumor cell survival and drug resistance. Cell. 2021 09 30; 184(20):5215-5229.e17.  View on PubMed
  11. Tiu GC, Kerr CH, Forester CM, Krishnarao PS, Rosenblatt HD, Raj N, Lantz TC, Zhulyn O, Bowen ME, Shokat L, Attardi LD, Ruggero D, Barna M. A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies. Dev Cell. 2021 07 26; 56(14):2089-2102.e11.  View on PubMed
  12. Forester CM, Ruggero D. Releasing the brake on protein synthesis in hematopoietic stem cells. Cell Stem Cell. 2021 07 01; 28(7):1183-1185.  View on PubMed
  13. Kuzuoglu-Ozturk D, Hu Z, Rama M, Devericks E, Weiss J, Chiang GG, Worland ST, Brenner SE, Goodarzi H, Gilbert LA, Ruggero D. Revealing molecular pathways for cancer cell fitness through a genetic screen of the cancer translatome. Cell Rep. 2021 06 29; 35(13):109321.  View on PubMed
  14. Chiu H, Buono R, Jackson LV, Herzog LO, Mallya S, Conn CS, Ruggero D, Fruman DA. Reduced eIF4E function impairs B-cell leukemia without altering normal B-lymphocyte function. iScience. 2021 Jul 23; 24(7):102748.  View on PubMed
  15. Christin Schmidt, Albertas Navickas, Frederique Zindy, Dana Farmer, Davide Ruggero, Hani Goodarzi, Martine F Roussel, Bjoern Schwer, William Weiss. OMIC-03. TRANSLATIONAL CONTROL IN MYC AND MYCN MEDULLOBLASTOMA. Neuro-Oncology. 2021 Jun 1; 23(Suppl 1):i37-i37.  View on PubMed
  16. Conn CS, Yang H, Tom HJ, Ikeda K, Oses-Prieto JA, Vu H, Oguri Y, Nair S, Gill RM, Kajimura S, DeBerardinis RJ, Burlingame AL, Ruggero D. The major cap-binding protein eIF4E regulates lipid homeostasis and diet-induced obesity. Nat Metab. 2021 02; 3(2):244-257.  View on PubMed
  17. Kovalski JR, Xu Y, Ruggero D. Examining Myc-Dependent Translation Changes in Cellular Homeostasis and Cancer. Methods Mol Biol. 2021; 2318:255-266.  View on PubMed
  18. Zhao N, Huang Y, Wang YH, Muir RK, Chen YC, Wei J, Hooshdaran N, Viswanath P, Seo Y, Ruggero D, Renslo AR, Evans MJ. Ferronostics: Measuring Tumoral Ferrous Iron with PET to Predict Sensitivity to Iron-Targeted Cancer Therapies. J Nucl Med. 2021 07 01; 62(7):949-955.  View on PubMed
  19. Lee-or Herzog, Bianca J. Lee, Thanh-Trang Vo, Honyin Chiu, Sharmila Mallya, Amos Fung, Mallika Singh, James Aggen, Nidhi Tibrewal, Jacqueline A.M. Smith, David Wildes, Ze'ev Ronai, Davide Ruggero, David A. Fruman. Abstract IA17: Strategies to target the mTORC1/eIF4F axis in B-cell leukemia and lymphoma. Molecular Cancer Research. 2020 Oct 1; 18(10_Supplement):ia17-ia17.  View on PubMed
  20. Wei J, Wang YH, Lee CY, Truillet C, Oh DY, Xu Y, Ruggero D, Flavell RR, VanBrocklin HF, Seo Y, Craik CS, Fong L, Wang CI, Evans MJ. An Analysis of Isoclonal Antibody Formats Suggests a Role for Measuring PD-L1 with Low Molecular Weight PET Radiotracers. Mol Imaging Biol. 2020 12; 22(6):1553-1561.  View on PubMed

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