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. 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. Nat Cell Biol. 2019 Jul; 21(7):889-899.
    View on PubMed
  2. 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. ACS Cent Sci. 2019 Apr 24; 5(4):727-736.
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  3. 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. Cell Host Microbe. 2019 Mar 13; 25(3):454-462.e6.
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  4. 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. Nat Med. 2019 Feb; 25(2):301-311.
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  5. 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. J Immunol. 2019 Jan 15; 202(2):579-590.
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  6. McMahon M, Ruggero D. A Translation Tuning HuDdle for Neurons. Mol Cell. 2018 07 19; 71(2):195-196.
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  7. McMahon M, Ruggero D. A wobbly road to drug resistance in melanoma: tRNA-modifying enzymes in translation reprogramming. EMBO J. 2018 08 01; 37(15).
    View on PubMed
  8. Robichaud N, Sonenberg N, Ruggero D, Schneider RJ. Translational Control in Cancer. Cold Spring Harb Perspect Biol. 2018 Jun 29.
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  9. 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).
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  10. 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 03 06; 115(10):2353-2358.
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  11. 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 01 08; 33(1):91-107.e6.
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  12. 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 01; 20(1):104-115.
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  13. Truitt ML, Ruggero D. New frontiers in translational control of the cancer genome. Nat Rev Cancer. 2017 04 24; 17(5):332.
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  14. Ruggero D, Shaw RJ. Editorial overview: Cell regulation: 1000 Flavors including chocolate and chili peppers. Curr Opin Cell Biol. 2017 04; 45:iv-vi.
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  15. 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.
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  16. 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.
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  17. Truitt ML, Ruggero D. New frontiers in translational control of the cancer genome. Nat Rev Cancer. 2016 04 26; 16(5):288-304.
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  18. 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.
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  19. 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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  20. 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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