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. 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 May 05.  View on PubMed
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu-Ozturk D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020 07; 583(7816):459-468.  View on PubMed
  14. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, O'Meara MJ, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Naing ZZC, Zhou Y, Peng S, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Shen W, Shi Y, Zhang Z, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Ramachandran R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Lin Y, Wankowicz SA, Bohn M, Trenker R, Young JM, Cavero D, Hiatt J, Roth T, Rathore U, Subramanian A, Noack J, Hubert M, Roesch F, Vallet T, Meyer B, White KM, Miorin L, Agard D, Emerman M, Ruggero D, García-Sastre A, Jura N, von Zastrow M, Taunton J, Schwartz O, Vignuzzi M, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor S, Fraser JS, Gross J, Sali A, Kortemme T, Beltrao P, Shokat K, Shoichet BK, Krogan NJ. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. bioRxiv. 2020 Mar 22.  View on PubMed
  15. Yichen Xu, Davide Ruggero. The Role of Translation Control in Tumorigenesis and Its Therapeutic Implications. Annual Review of Cancer Biology. 2020 Mar 4; 4(1):1-21.  View on PubMed
  16. Wei J, Leung K, Truillet C, Ruggero D, Wells JA, Evans MJ. Profiling the Surfaceome Identifies Therapeutic Targets for Cells with Hyperactive mTORC1 Signaling. Mol Cell Proteomics. 2020 02; 19(2):294-307.  View on PubMed
  17. Craig M Forester, Gun Woo-Byeon, Juan Oses-Prieto, Al Burlingame, Maria Barna, Davide M Ruggero. Regulation of eIF4E Guides a Unique Translational Program to Steer Erythroid Maturation. Blood. 2019 Nov 13; 134(Supplement_1):156-156.  View on PubMed
  18. McMahon M, Contreras A, Holm M, Uechi T, Forester CM, Pang X, Jackson C, Calvert ME, Chen B, Quigley DA, Luk JM, Kelley RK, Gordan JD, Gill RM, Blanchard SC, Ruggero D. A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS. Elife. 2019 09 03; 8.  View on PubMed
  19. Tameire F, Verginadis II, Leli NM, Polte C, Conn CS, Ojha R, Salinas CS, Chinga F, Monroy AM, Fu W, Wang P, Kossenkov A, Ye J, Amaravadi RK, Ignatova Z, Fuchs SY, Diehl JA, Ruggero D, Koumenis C. Author Correction: ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression. Nat Cell Biol. 2019 Aug; 21(8):1052.  View on PubMed
  20. Fish L, Navickas A, Culbertson B, Xu Y, Nguyen HCB, Zhang S, Hochman M, Okimoto R, Dill BD, Molina H, Najafabadi HS, Alarcón C, Ruggero D, Goodarzi H. Nuclear TARBP2 Drives Oncogenic Dysregulation of RNA Splicing and Decay. Mol Cell. 2019 09 05; 75(5):967-981.e9.  View on PubMed

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