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 is President of the Helen Diller Family Comprehensive Cancer Center at University of California, San Francisco and Senior Vice President for clinical services, UCSF Health. Ashworth was a key member of the team that discovered the BRCA2 gene in 1995, which is linked to an increased risk of breast, ovarian and other cancers. In 2005, his lab described a way to exploit genetic weaknesses (using synthetic lethality) in cancer cells with mutated BRCA1 or BRCA2 genes, leading to a new approach to cancer treatment, PARP inhibition. Four different PARP inhibitors have now been approved by the FDA for the treatment of ovarian, breast, pancreatic and prostate cancer based on this observation, which was named by Nature in the top 20 discoveries in cancer in the 21st century. He continues to develop new treatments for cancer using genetic principles.

He has received a number of awards and prizes many of which recognize the innovative and translational nature of his work as well as its clinical impact. He is an elected member of the European Molecular Biology Organization (EMBO) and a Fellow of the Academy of Medical Sciences, the American Association of Arts and Sciences, the American Association of Cancer Research and the Royal Society. Prizes include the European Society of Medical Oncology (ESMO) Lifetime Achievement Award, the David T. Workman Memorial Award of the Samuel Waxman Cancer Research Foundation, the Meyenburg Foundation’s Cancer Research Award, the Genetics Society Medal, the Susan G Komen Brinker award and the inaugural Basser Global Prize.

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

  • 2023
    ASCO 2023 Science of Oncology Award and Lecture
  • 2023
    Memorial Sloan Kettering Cancer Centerʻs C. Chester Stock Award Lectureship
  • 2020
    Emerson Collective Cancer Research Award
  • 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. Chen H, Gou X, Mao Y, O'Leary PC, Diolaiti ME, Ashworth A. PARP7 Inhibitors and AHR Agonists Act Synergistically across a Wide Range of Cancer Models. Mol Cancer Ther. 2025 Jan 02; 24(1):56-68.  View on PubMed
  2. Chesner LN, Polesso F, Graff JN, Hawley JE, Smith AK, Lundberg A, Das R, Shenoy T, Sjöström M, Zhao F, Hu YM, Linder S, Chen WS, Hawkins RM, Shrestha R, Zhu X, Foye A, Li H, Kim LM, Bhalla M, O'loughlin T, Kuzuoglu-Ozturk D, Hua JT, Badura ML, Wilkinson S, Trostel SY, Bergman AM, Ruggero D, Drake CG, Sowalsky AG, Fong L, Cooperberg MR, Zwart W, Guan X, Ashworth A, Xia Z, Quigley DA, Gilbert LA, Feng FY, Moran AE. Androgen receptor inhibition increases MHC Class I expression and improves immune response in prostate cancer. Cancer Discov. 2024 Dec 05.  View on PubMed
  3. Chou J, Robinson TM, Egusa EA, Lodha R, Zhang M, Badura M, Mikayelyan M, Delavan HM, Swinderman J, Wilson C, Zhu J, Das R, Nguyen M, Loehr A, Golsorkhi T, Simmons A, Abida W, Chinnaiyan AM, Arkin MR, Small EJ, Quigley DA, Yang L, Kim M, Ashworth A, Feng FY. Synthetic Lethal Targeting of CDK12-Deficient Prostate Cancer with PARP Inhibitors. Clin Cancer Res. 2024 Dec 02; 30(23):5445-5458.  View on PubMed
  4. Bedia JS, Huang YW, Gonzalez AD, Gonzalez VD, Funingana IG, Rahil Z, Mike A, Lowber A, Vias M, Ashworth A, Brenton JD, Fantl WJ. Coordinated protein modules define DNA damage responses to carboplatin at single cell resolution in human ovarian carcinoma models. bioRxiv. 2024 Nov 26.  View on PubMed
  5. Yang Y, Badura ML, O'Leary PC, Delavan HM, Robinson TM, Egusa EA, Zhong X, Swinderman JT, Li H, Zhang M, Kim M, Ashworth A, Feng FY, Chou J, Yang L. Transcription and DNA replication collisions lead to large tandem duplications and expose targetable therapeutic vulnerabilities in cancer. Nat Cancer. 2024 Dec; 5(12):1885-1901.  View on PubMed
  6. Choudhury A, Cady MA, Lucas CG, Najem H, Phillips JJ, Palikuqi B, Zakimi N, Joseph T, Birrueta JO, Chen WC, Oberheim Bush NA, 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. Perivascular NOTCH3+ Stem Cells Drive Meningioma Tumorigenesis and Resistance to Radiotherapy. Cancer Discov. 2024 Oct 04; 14(10):1823-1837.  View on PubMed
  7. Chen H, Sarah L, Pucciarelli D, Mao Y, Diolaiti ME, Fujimori DG, Ashworth A. Histone demethylase enzymes KDM5A and KDM5B modulate immune response by suppressing transcription of endogenous retroviral elements. bioRxiv. 2024 Sep 25.  View on PubMed
  8. Suryawanshi RK, Jaishankar P, Correy GJ, Rachman MM, O'Leary PC, Taha TY, Zapatero-Belinchón FJ, McCavittMalvido M, Doruk YU, Stevens MGV, Diolaiti ME, Jogalekar MP, Richards AL, Montano M, Rosecrans J, Matthay M, Togo T, Gonciarz RL, Gopalkrishnan S, Neitz RJ, Krogan NJ, Swaney DL, Shoichet BK, Ott M, Renslo AR, Ashworth A, Fraser JS. The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2. bioRxiv. 2024 Aug 29.  View on PubMed
  9. Chen DF, Roe LT, Li Y, Borges AL, Zhang JY, Babbar P, Maji S, Stevens MGV, Correy GJ, Diolaiti ME, Smith DH, Ashworth A, Stroud RM, Kelly MJS, Bondy-Denomy J, Fraser JS. AcrIF11 is a potent CRISPR-specific ADP-ribosyltransferase encoded by phage and plasmid. bioRxiv. 2024 Aug 26.  View on PubMed
  10. Correy GJ, Rachman M, Togo T, Gahbauer S, Doruk YU, Stevens M, Jaishankar P, Kelley B, Goldman B, Schmidt M, Kramer T, Ashworth A, Riley P, Shoichet BK, Renslo AR, Walters WP, Fraser JS. Extensive exploration of structure activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment merging and active learning. bioRxiv. 2024 Aug 26.  View on PubMed
  11. Maldonado E, Rathmell WK, Shapiro GI, Takebe N, Rodon J, Mahalingam D, Trikalinos NA, Kalebasty AR, Parikh M, Boerner SA, Balido C, Krings G, Burns TF, Bergsland EK, Munster PN, Ashworth A, LoRusso P, Aggarwal RR. A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170). Cancer Res Commun. 2024 07 01; 4(7):1793-1801.  View on PubMed
  12. Lu L, Gou X, Tan SK, Mann SI, Yang H, Zhong X, Gazgalis D, Valdiviezo J, Jo H, Wu Y, Diolaiti ME, Ashworth A, Polizzi NF, DeGrado WF. De novo design of drug-binding proteins with predictable binding energy and specificity. Science. 2024 Apr 05; 384(6691):106-112.  View on PubMed
  13. Van Loon K, Breithaupt L, Ng D, DeBoer RJ, Buckle GC, Bialous S, Hiatt RA, Volberding P, Hermiston ML, Ashworth A. A roadmap to establishing global oncology as a priority initiative within a National Cancer Institute-designated cancer center. J Natl Cancer Inst. 2024 Mar 07; 116(3):345-351.  View on PubMed
  14. Yang Y, Badura ML, O'Leary PC, Delavan HM, Robinson TM, Egusa EA, Zhong X, Swinderman JT, Li H, Zhang M, Kim M, Ashworth A, Feng FY, Chou J, Yang L. Large tandem duplications in cancer result from transcription and DNA replication collisions. medRxiv. 2024 Jan 10.  View on PubMed
  15. Lu L, Gou X, Tan SK, Mann SI, Yang H, Zhong X, Gazgalis D, Valdiviezo J, Jo H, Wu Y, Diolaiti ME, Ashworth A, Polizzi NF, DeGrado WF. De novo design of drug-binding proteins with predictable binding energy and specificity. bioRxiv. 2023 Dec 23.  View on PubMed
  16. Bank EM, Small EJ, Ashworth A, Hiatt RA. Cancer Research in 2030: A unique strategic planning process at a comprehensive cancer center. Prev Oncol Epidemiol. 2023; 1(1):1-9.  View on PubMed
  17. Taha TY, Suryawanshi RK, Chen IP, Correy GJ, McCavitt-Malvido M, O'Leary PC, Jogalekar MP, Diolaiti ME, Kimmerly GR, Tsou CL, Gascon R, Montano M, 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 in vivo. PLoS Pathog. 2023 08; 19(8):e1011614.  View on PubMed
  18. 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
  19. 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
  20. 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

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