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/NCI, 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/NCI, Sponsor Award ID: R01CA154916
  • 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/NCI, Sponsor Award ID: R01CA140456
  • September 1, 2014 - June 30, 2019 - MYCN, mTOR and translation control in medulloblastoma, Co-Principal Investigator. Sponsor: NIH/NINDS, Sponsor Award ID: R01NS089868

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. Wei J, Leung K, Truillet C, Ruggero D, Wells JA, Evans MJ Profiling the Surfaceome Identifies Therapeutic Targets for Cells with Hyperactive mTORC1 Signaling.  View on PubMed
  2. Zhao N, Huang Y, Wang YH, Muir RK, Chen YC, Hooshdaran N, Wei J, 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.  View on PubMed
  3. 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.  View on PubMed
  4. 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.  View on PubMed
  5. 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.  View on PubMed
  6. Yichen Xu, Davide Ruggero The Role of Translation Control in Tumorigenesis and Its Therapeutic Implications.  View on PubMed
  7. Wei J, Leung K, Truillet C, Ruggero D, Wells JA, Evans MJ Profiling the Surfaceome Identifies Therapeutic Targets for Cells with Hyperactive mTORC1 Signaling.  View on PubMed
  8. 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.  View on PubMed
  9. 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.  View on PubMed
  10. 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.  View on PubMed
  11. 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.  View on PubMed
  12. Tameire F, Verginadis II, Leli NM, Polte C, Conn CS, Ojha R, Salas Salinas C, Chinga F, Monroy AM, Fu W, Wang P, Kossenkov A, Ye J, Amaravadi RK, Ignatova Z, Fuchs SY, Diehl JA, Ruggero D, Koumenis C ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression.  View on PubMed
  13. Robichaud N, Sonenberg N, Ruggero D, Schneider RJ Translational Control in Cancer.  View on PubMed
  14. Muir RK, Zhao N, Wei J, Wang YH, Moroz A, Huang Y, Chen YC, Sriram R, Kurhanewicz J, Ruggero D, Renslo AR, Evans MJ Measuring Dynamic Changes in the Labile Iron Pool in Vivo with a Reactivity-Based Probe for Positron Emission Tomography.  View on PubMed
  15. Moss SM, Taylor IR, Ruggero D, Gestwicki JE, Shokat KM, Mukherjee S A Legionella pneumophila Kinase Phosphorylates the Hsp70 Chaperone Family to Inhibit Eukaryotic Protein Synthesis.  View on PubMed
  16. Xu Y, Poggio M, Jin HY, Shi Z, Forester CM, Wang Y, Stumpf CR, Xue L, Devericks E, So L, Nguyen HG, Griselin A, Gordan JD, Umetsu SE, Reich SH, Worland ST, Asthana S, Barna M, Webster KR, Cunningham JT, Ruggero D Translation control of the immune checkpoint in cancer and its therapeutic targeting.  View on PubMed
  17. Chiu H, Jackson LV, Oh KI, Mai A, Ronai ZA, Ruggero D, Fruman DA The mTORC1/4E-BP/eIF4E Axis Promotes Antibody Class Switching in B Lymphocytes.  View on PubMed
  18. McMahon M, Ruggero D A Translation Tuning HuDdle for Neurons.  View on PubMed
  19. McMahon M, Ruggero D A wobbly road to drug resistance in melanoma: tRNA-modifying enzymes in translation reprogramming.  View on PubMed
  20. Nguyen HG, Conn CS, Kye Y, Xue L, Forester CM, Cowan JE, Hsieh AC, Cunningham JT, Truillet C, Tameire F, Evans MJ, Evans CP, Yang JC, Hann B, Koumenis C, Walter P, Carroll PR, Ruggero D Development of a stress response therapy targeting aggressive prostate cancer.  View on PubMed

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