University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Davide Ruggero, PhD

Davide Ruggero, PhD

Professor, Department of Urology, UCSF
Helen Diller Family Chair in Basic Cancer Research, UCSF

Cancer Center Program Memberships

Prostate Cancer

Research Summary

My laboratory has been a pioneer in understanding the molecular mechanisms by which impairments in accurate control of RNA modification, mRNA translation, cell growth, and overall cellular protein synthesis rates lead to cancer and human disease. Our research began with the goal of identifying novel mechanisms for cancer initiation at the post-genomic level. Our research is uncovering that deregulations in the proteome may serve as a common mechanism elicited by multiple oncogenic signals (e.g., PI3K-AKT-mTOR, Ras, Myc) to cause cellular transformation and may overshadow the effects on the transcriptome. Global analysis of the deregulated proteome during cancer formation utilizing novel polysome microarrays pioneered by our lab indicates that control of protein production provides a highly specific, robust, and rapid response to oncogenic stimuli. These findings strongly suggest that a radical shift in the composition of mRNAs associated with actively translating polysomes may lead to an immediate neoplastic phenotype upon an oncogenic lesion. We have complemented these studies by generating the first mouse models for components of the translation machinery found mutated in human disease and cancer. Utilizing biochemical, molecular, and genetic approaches within the context of these unique animal models, it is our overall goal to uncover novel mechanisms for cancer initiation at the post-genomic level. These results have been instrumental in the design of a new generation of compounds that modulate the cellular proteome at the post-genomic level and act as cancer therapeutic agents.

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


Professional Experience

  • 1998-2000
    Post-doctoral fellow in the Laboratory of Molecular and Developmental Biology of P.P. Pandolfi, Memorial Sloan Kettering Cancer Center, New York
  • 2001-2003
    Research Associate, in the Laboratory of Molecular and Developmental Biology of P.P. Pandolfi, Memorial Sloan Kettering Cancer Center, New York
  • 2004-2007
    Associate Member, Fox Chase Cancer Center, Philadelphia, PA
  • 2007-2010
    Assistant Professor, Dept. of Urology, University of California, San Francisco, CA
  • 2010-2014
    Associate Professor, Dept. of Urology, University of California, San Francisco, CA
  • 2014-present
    Professor, Dept. of Urology, University of California, San Francisco, CA

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

Selected Publications

  1. 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. Sci Transl Med. 2018 May 02; 10(439).
    View on PubMed
  2. Forester CM, Zhao Q, Phillips NJ, Urisman A, Chalkley RJ, Oses-Prieto JA, Zhang L, Ruggero D, Burlingame AL. Revealing nascent proteomics in signaling pathways and cell differentiation. Proc Natl Acad Sci U S A. 2018 Mar 06; 115(10):2353-2358.
    View on PubMed
  3. Gwinn DM, Lee AG, Briones-Martin-Del-Campo M, Conn CS, Simpson DR, Scott AI, Le A, Cowan TM, Ruggero D, Sweet-Cordero EA. Oncogenic KRAS Regulates Amino Acid Homeostasis and Asparagine Biosynthesis via ATF4 and Alters Sensitivity to L-Asparaginase. Cancer Cell. 2018 Jan 08; 33(1):91-107.e6.
    View on PubMed
  4. Bu Y, Yoshida A, Chitnis N, Altman BJ, Tameire F, Oran A, Gennaro V, Armeson KE, McMahon SB, Wertheim GB, Dang CV, Ruggero D, Koumenis C, Fuchs SY, Diehl JA. A PERK-miR-211 axis suppresses circadian regulators and protein synthesis to promote cancer cell survival. Nat Cell Biol. 2018 Jan; 20(1):104-115.
    View on PubMed
  5. Truitt ML, Ruggero D. New frontiers in translational control of the cancer genome. Nat Rev Cancer. 2017 04 24; 17(5):332.
    View on PubMed
  6. Ruggero D, Shaw RJ. Editorial overview: Cell regulation: 1000 Flavors including chocolate and chili peppers. Curr Opin Cell Biol. 2017 Apr; 45:iv-vi.
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  7. Truillet C, Cunningham JT, Parker MFL, Huynh LT, Conn CS, Ruggero D, Lewis JS, Evans MJ. Noninvasive Measurement of mTORC1 Signaling with 89Zr-Transferrin. Clin Cancer Res. 2017 Jun 15; 23(12):3045-3052.
    View on PubMed
  8. So L, Lee J, Palafox M, Mallya S, Woxland CG, Arguello M, Truitt ML, Sonenberg N, Ruggero D, Fruman DA. The 4E-BP-eIF4E axis promotes rapamycin-sensitive growth and proliferation in lymphocytes. Sci Signal. 2016 05 31; 9(430):ra57.
    View on PubMed
  9. Truitt ML, Ruggero D. New frontiers in translational control of the cancer genome. Nat Rev Cancer. 2016 04 26; 16(5):288-304.
    View on PubMed
  10. Hsieh AC, Nguyen HG, Wen L, Edlind MP, Carroll PR, Kim W, Ruggero D. Cell type-specific abundance of 4EBP1 primes prostate cancer sensitivity or resistance to PI3K pathway inhibitors. Sci Signal. 2015 Nov 17; 8(403):ra116.
    View on PubMed
  11. Truitt ML, Conn CS, Shi Z, Pang X, Tokuyasu T, Coady AM, Seo Y, Barna M, Ruggero D. Differential Requirements for eIF4E Dose in Normal Development and Cancer. Cell. 2015 Jul 02; 162(1):59-71.
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  12. Fujita-Sato S, Galeas J, Truitt M, Pitt C, Urisman A, Bandyopadhyay S, Ruggero D, McCormick F. Enhanced MET Translation and Signaling Sustains K-Ras-Driven Proliferation under Anchorage-Independent Growth Conditions. Cancer Res. 2015 Jul 15; 75(14):2851-62.
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  13. Sheridan CM, Grogan TR, Nguyen HG, Galet C, Rettig MB, Hsieh AC, Ruggero D. YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence. Oncotarget. 2015 Apr 10; 6(10):7470-80.
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  14. Pelletier J, Graff J, Ruggero D, Sonenberg N. Targeting the eIF4F translation initiation complex: a critical nexus for cancer development. Cancer Res. 2015 Jan 15; 75(2):250-63.
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  15. McMahon M, Contreras A, Ruggero D. Small RNAs with big implications: new insights into H/ACA snoRNA function and their role in human disease. Wiley Interdiscip Rev RNA. 2015 Mar-Apr; 6(2):173-89.
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  16. Ruggero D, Shimamura A. Marrow failure: a window into ribosome biology. Blood. 2014 Oct 30; 124(18):2784-92.
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  17. Cunningham JT, Moreno MV, Lodi A, Ronen SM, Ruggero D. Protein and nucleotide biosynthesis are coupled by a single rate-limiting enzyme, PRPS2, to drive cancer. Cell. 2014 May 22; 157(5):1088-103.
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  18. Barna M, Ruggero D. Tailor made protein synthesis for HSCs. Cell Stem Cell. 2014 Apr 03; 14(4):423-4.
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  19. Han K, Jaimovich A, Dey G, Ruggero D, Meyuhas O, Sonenberg N, Meyer T. Parallel measurement of dynamic changes in translation rates in single cells. Nat Methods. 2014 Jan; 11(1):86-93.
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  20. Stumpf CR, Moreno MV, Olshen AB, Taylor BS, Ruggero D. The translational landscape of the mammalian cell cycle. Mol Cell. 2013 Nov 21; 52(4):574-82.
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