Alan Ashworth, PhD, FRS

E. Dixon Heise Distinguished Professor in Oncology, UCSF

President, UCSF Helen Diller Family Comprehensive Cancer Center; Senior Vice President for Cancer Services, UCSF Health; Professor of Medicine, Division of Hematology/Oncology, Department of Medicine, UCSF

Cancer Center Program Membership

Molecular Oncology

Research Summary

Alan Ashworth, PhD, FRS, is President of the UCSF Helen Diller Family Comprehensive Cancer Center, and Sr. Vice President for Cancer Services with UCSF Health. Prior to joining UCSF in January 2015, he served as Chief Executive of the Institute of Cancer Research (ICR) and the Director of the Breakthrough Breast Cancer Research Centre in London, United Kingdom.

A translational biologist and laboratory researcher, Ashworth's research focuses on understanding breast cancer genetics to improve the treatment and care of patients. He was a key part of the team that identified the BRCA2 breast cancer susceptibility gene that is linked to an increased risk for some types of cancer. Ten years later, he discovered how to kill BRCA1- and 2-related tumor cells by treating them with PARP inhibitors which are drugs that increase the damage caused by the broken DNA repair machinery in those cells. This exemplifies the principle of synthetic lethality as cancer therapy. Three different PARP inhibitors are now approved by the FDA.

In 2016, Ashworth and UCSF's Pamela Munster, MD, established the Center for BRCA Research, one of only two such centers in the US. The mission of the Center is to provide a place for families with BRCA and other mutations to receive personalized care and planning for their long-term health and well-being. He also started the San Francisco Cancer Initiative (SF CAN) that launched in 2016. SF CAN is the first comprehensive cancer plan for a major city and its partners include the City of San Francisco and numerous health and community organizations. Ashworth also chairs the UC Cancer Consortium, an alliance of the five UC cancer centers holding comprehensive cancer center status, the highest designation possible from the National Institutes of Health's National Cancer Institute. The Consortium's projects include precision medicine, clinical trials, population health science, best practices in harnessing big data to improve health, and political engagement for public benefit.

Ashworth is an elected member of EMBO, the Academy of Medical Sciences, and a Fellow of the Royal Society. He has received a number of scientific prizes and awards, including The European Society of Medical Oncology Lifetime Achievement Award, the David T. Workman Memorial Award of the Samuel Waxman Cancer Research Foundation, the Meyenburg Foundation's Cancer Research Award, the Basser Global Prize, the Genetics Society Medal, and the 2017 Brinker Award for Scientific Distinction in Basic Science from the Susan G. Komen Foundation.

Research Funding

  • September 1, 2018 - August 31, 2023 - DNA repair alterations in metastatic prostate cancer: functional and therapeutic implications , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA230516
  • August 5, 1999 - May 31, 2023 - Cancer Center Support Grant , Principal Investigator . Sponsor: NIH, Sponsor Award ID: P30CA082103

Education

1978 – 1981, BSc (Hons), Chemistry and Biochemistry, Imperial College of Science and Technology, University of London
1981 – 1984, PhD, Biochemistry, University College London
1986 – 1988, Postdoctoral Fellow, The Institute of Cancer Research
1984 – 1986, Postdoctoral Fellow, Department of Biochemistry, University College London

Honors & Awards

  • 2018
    Elected as Fellow, American Association for Cancer Research
  • 2018
    Pioneer Award, Precision Medicine World Conference
  • 2017
    Brinker Award for Scientific Distinction in Basic Science, Susan G. Komen
  • 2016
    Drexel Prize in Cancer Biology
  • 2016
    Appointed to American Association for Cancer Research Board of Directors
  • 2015
    Genetics Society Medal
  • 2015
    Spirit of Empowerment Award, Facing Our Risk of Cancer Empowered (FORCE)
  • 2013
    Basser Global Prize
  • 2012
    Scientist in Residence - University Duisberg-Essen/Essener Sparkasse
  • 2012
    Pathological Society of Great Britain and Ireland’s Goudie Medal
  • 2010
    AACR Distinguished Lectureship in Breast Cancer, San Antonio
  • 2010
    Meyenburg Foundation Cancer Research Award
  • 2010
    Samuel Waxman Cancer Research Foundation David Workman Memorial Award
  • 2009
    Elected Fellow of the European Academy of Cancer Sciences
  • 2009
    ESMO Lifetime Achievement Award
  • 2008
    Elected Fellow of the Royal Society
  • 2002
    Elected Fellow of the Academy of Medical Sciences
  • 1999
    Elected to EMBO
  • 1991
    British Postgraduate Medical Federation Prize

Selected Publications

  1. Choudhury A, Cady MA, Lucas CG, Najem H, Phillips JJ, Palikuqi B, Zakimi N, Joseph T, Birrueta JO, Chen WC, Bush NAO, Hervey-Jumper SL, Klein OD, Toedebusch CM, Horbinski CM, Magill ST, Bhaduri A, Perry A, Dickinson PJ, Heimberger AB, Ashworth A, Crouch EE, Raleigh DR. NOTCH3 drives meningioma tumorigenesis and resistance to radiotherapy. bioRxiv. 2023 Jul 11.  View on PubMed
  2. Taha TY, Suryawanshi RK, Chen IP, Correy GJ, O'Leary PC, Jogalekar MP, McCavitt-Malvido M, Diolaiti ME, Kimmerly GR, Tsou CL, Martinez-Sobrido L, Krogan NJ, Ashworth A, Fraser JS, Ott M. A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication and pathogenesis in vivo. bioRxiv. 2023 May 10.  View on PubMed
  3. Mandair D, Reis-Filho JS, Ashworth A. Biological insights and novel biomarker discovery through deep learning approaches in breast cancer histopathology. NPJ Breast Cancer. 2023 Apr 06; 9(1):21.  View on PubMed
  4. Chou J, Egusa EA, Wang S, Badura ML, Lee F, Bidkar AP, Zhu J, Shenoy T, Trepka K, Robinson TM, Steri V, Huang J, Wang Y, Small EJ, Chan E, Stohr BA, Ashworth A, Delafontaine B, Rottey S, Cooke KS, Hashemi Sadraei N, Yu B, Salvati M, Bailis JM, Feng FY, Flavell RR, Aggarwal R. Immunotherapeutic Targeting and PET Imaging of DLL3 in Small-Cell Neuroendocrine Prostate Cancer. Cancer Res. 2023 01 18; 83(2):301-315.  View on PubMed
  5. Calses PC, Pham VC, Guarnaccia AD, Choi M, Verschueren E, Bakker ST, Pham TH, Hinkle T, Liu C, Chang MT, Kljavin N, Bakalarski C, Haley B, Zou J, Yan C, Song X, Lin X, Rowntree R, Ashworth A, Dey A, Lill JR. TEAD Proteins Associate With DNA Repair Proteins to Facilitate Cellular Recovery From DNA Damage. Mol Cell Proteomics. 2023 02; 22(2):100496.  View on PubMed
  6. Gahbauer S, Correy GJ, Schuller M, Ferla MP, Doruk YU, Rachman M, Wu T, Diolaiti M, Wang S, Neitz RJ, Fearon D, Radchenko DS, Moroz YS, Irwin JJ, Renslo AR, Taylor JC, Gestwicki JE, von Delft F, Ashworth A, Ahel I, Shoichet BK, Fraser JS. Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2. Proc Natl Acad Sci U S A. 2023 01 10; 120(2):e2212931120.  View on PubMed
  7. Thomas A, Fontaine SD, Diolaiti ME, Desai P, Kumar R, Takahashi N, Sciuto L, Nichols S, Ashworth A, Feng FY, Ashley GW, Nguyen M, Pommier Y, Santi DV. PLX038: A Long-Acting Topoisomerase I Inhibitor With Robust Antitumor Activity in ATM-Deficient Tumors and Potent Synergy With PARP Inhibitors. Mol Cancer Ther. 2022 Nov 03; 21(11):1722-1728.  View on PubMed
  8. O'Leary PC, Chen H, Doruk YU, Williamson T, Polacco B, McNeal AS, Shenoy T, Kale N, Carnevale J, Stevenson E, Quigley DA, Chou J, Feng FY, Swaney DL, Krogan NJ, Kim M, Diolaiti ME, Ashworth A. Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2. Cancer Res. 2022 11 02; 82(21):3950-3961.  View on PubMed
  9. Sjöström M, Zhao SG, Levy S, Zhang M, Ning Y, Shrestha R, Lundberg A, Herberts C, Foye A, Aggarwal R, Hua JT, Li H, Bergamaschi A, Maurice-Dror C, Maheshwari A, Chen S, Ng SWS, Ye W, Petricca J, Fraser M, Chesner L, Perry MD, Moreno-Rodriguez T, Chen WS, Alumkal JJ, Chou J, Morgans AK, Beer TM, Thomas GV, Gleave M, Lloyd P, Phillips T, McCarthy E, Haffner MC, Zoubeidi A, Annala M, Reiter RE, Rettig MB, Witte ON, Fong L, Bose R, Huang FW, Luo J, Bjartell A, Lang JM, Mahajan NP, Lara PN, Evans CP, Tran PT, Posadas EM, He C, Cui XL, Huang J, Zwart W, Gilbert LA, Maher CA, Boutros PC, Chi KN, Ashworth A, Small EJ, He HH, Wyatt AW, Quigley DA, Feng FY. The 5-Hydroxymethylcytosine Landscape of Prostate Cancer. Cancer Res. 2022 11 02; 82(21):3888-3902.  View on PubMed
  10. Carnevale J, Shifrut E, Kale N, Nyberg WA, Blaeschke F, Chen YY, Li Z, Bapat SP, Diolaiti ME, O'Leary P, Vedova S, Belk J, Daniel B, Roth TL, Bachl S, Anido AA, Prinzing B, Ibañez-Vega J, Lange S, Haydar D, Luetke-Eversloh M, Born-Bony M, Hegde B, Kogan S, Feuchtinger T, Okada H, Satpathy AT, Shannon K, Gottschalk S, Eyquem J, Krenciute G, Ashworth A, Marson A. RASA2 ablation in T cells boosts antigen sensitivity and long-term function. Nature. 2022 09; 609(7925):174-182.  View on PubMed
  11. Gahbauer S, Correy GJ, Schuller M, Ferla MP, Doruk YU, Rachman M, Wu T, Diolaiti M, Wang S, Neitz RJ, Fearon D, Radchenko D, Moroz Y, Irwin JJ, Renslo AR, Taylor JC, Gestwicki JE, von Delft F, Ashworth A, Ahel I, Shoichet BK, Fraser JS. Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 Macrodomain of SARS-CoV-2. bioRxiv. 2022 Jul 28.  View on PubMed
  12. Chen H, Diolaiti ME, O'Leary PC, Rojc A, Krogan NJ, Kim M, Ashworth A. A Whole-Genome CRISPR Screen Identifies AHR Loss as a Mechanism of Resistance to a PARP7 Inhibitor. Mol Cancer Ther. 2022 07 05; 21(7):1076-1089.  View on PubMed
  13. Belk JA, Yao W, Ly N, Freitas KA, Chen YT, Shi Q, Valencia AM, Shifrut E, Kale N, Yost KE, Duffy CV, Daniel B, Hwee MA, Miao Z, Ashworth A, Mackall CL, Marson A, Carnevale J, Vardhana SA, Satpathy AT. Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence. Cancer Cell. 2022 07 11; 40(7):768-786.e7.  View on PubMed
  14. Correy GJ, Kneller DW, Phillips G, Pant S, Russi S, Cohen AE, Meigs G, Holton JM, Gahbauer S, Thompson MC, Ashworth A, Coates L, Kovalevsky A, Meilleur F, Fraser JS. The mechanisms of catalysis and ligand binding for the SARS-CoV-2 NSP3 macrodomain from neutron and x-ray diffraction at room temperature. Sci Adv. 2022 May 27; 8(21):eabo5083.  View on PubMed
  15. Guix I, Liu Q, Pujana MA, Ha P, Piulats J, Linares I, Guedea F, Mao JH, Lazar A, Chapman J, Yom SS, Ashworth A, Barcellos-Hoff MH. Validation of Anticorrelated TGFβ Signaling and Alternative End-Joining DNA Repair Signatures that Predict Response to Genotoxic Cancer Therapy. Clin Cancer Res. 2022 04 01; 28(7):1372-1382.  View on PubMed
  16. Hiatt RA, Sibley A, Venkatesh B, Cheng J, Dixit N, Fox R, Ling P, Nguyen T, Oh D, Palmer NR, Pasick RJ, Potter MB, Somsouk M, Vargas RA, Vijayaraghavan M, Ashworth A. From Cancer Epidemiology to Policy and Practice: the Role of a Comprehensive Cancer Center. Curr Epidemiol Rep. 2022; 9(1):10-21.  View on PubMed
  17. Byrnes JR, Weeks AM, Shifrut E, Carnevale J, Kirkemo L, Ashworth A, Marson A, Wells JA. Hypoxia Is a Dominant Remodeler of the Effector T Cell Surface Proteome Relative to Activation and Regulatory T Cell Suppression. Mol Cell Proteomics. 2022 04; 21(4):100217.  View on PubMed
  18. Correy GJ, Kneller DW, Phillips G, Pant S, Russi S, Cohen AE, Meigs G, Holton JM, Gahbauer S, Thompson MC, Ashworth A, Coates L, Kovalevsky A, Meilleur F, Fraser JS. The mechanisms of catalysis and ligand binding for the SARS-CoV-2 NSP3 macrodomain from neutron and X-ray diffraction at room temperature. bioRxiv. 2022 Feb 09.  View on PubMed
  19. Kim M, Park J, Bouhaddou M, Kim K, Rojc A, Modak M, Soucheray M, McGregor MJ, O'Leary P, Wolf D, Stevenson E, Foo TK, Mitchell D, Herrington KA, Muñoz DP, Tutuncuoglu B, Chen KH, Zheng F, Kreisberg JF, Diolaiti ME, Gordan JD, Coppé JP, Swaney DL, Xia B, van 't Veer L, Ashworth A, Ideker T, Krogan NJ. A protein interaction landscape of breast cancer. Science. 2021 Oct; 374(6563):eabf3066.  View on PubMed
  20. Monk EJM, Rautemaa-Richardson R, Felton T, Montalti A, Parkes M, Templeton R, Ashworth A, Garcia M, Barker J, Thomas S. Incidence of candidaemia in prolonged venovenous extracorporeal membrane oxygenation. J Hosp Infect. 2022 Jan; 119:49-53.  View on PubMed

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