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. 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
  2. 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 PARP7 inhibitor resistance. Mol Cancer Ther. 2022 Apr 19.  View on PubMed
  3. 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 Apr 01; 28(7):1372-1382.  View on PubMed
  4. 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
  5. 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 Apr; 21(4):100217.  View on PubMed
  6. 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
  7. 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
  8. 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
  9. Lüscher B, Ahel I, Altmeyer M, Ashworth A, Bai P, Chang P, Cohen M, Corda D, Dantzer F, Daugherty MD, Dawson TM, Dawson VL, Deindl S, Fehr AR, Feijs KLH, Filippov DV, Gagné JP, Grimaldi G, Guettler S, Hoch NC, Hottiger MO, Korn P, Kraus WL, Ladurner A, Lehtiö L, Leung AKL, Lord CJ, Mangerich A, Matic I, Matthews J, Moldovan GL, Moss J, Natoli G, Nielsen ML, Niepel M, Nolte F, Pascal J, Paschal BM, Pawlowski K, Poirier GG, Smith S, Timinszky G, Wang ZQ, Yélamos J, Yu X, Zaja R, Ziegler M. ADP-ribosyltransferases, an update on function and nomenclature. FEBS J. 2021 Jul 29.  View on PubMed
  10. Das R, Sjöström M, Shrestha R, Yogodzinski C, Egusa EA, Chesner LN, Chen WS, Chou J, Dang DK, Swinderman JT, Ge A, Hua JT, Kabir S, Quigley DA, Small EJ, Ashworth A, Feng FY, Gilbert LA. An integrated functional and clinical genomics approach reveals genes driving aggressive metastatic prostate cancer. Nat Commun. 2021 07 29; 12(1):4601.  View on PubMed
  11. Ashworth A. ATR Inhibitors and Paclitaxel in Melanoma. Clin Cancer Res. 2021 09 01; 27(17):4667-4668.  View on PubMed
  12. Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, Young ID, Carvalho Martins L, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT, QCRG Structural Biology Consortium, Aimon A, Bennett JM, Brandao Neto J, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs MR, Gorrie-Stone TJ, Holton JM, Johnson MG, Krojer T, Meigs G, Powell AJ, Rack JGM, Rangel VL, Russi S, Skyner RE, Smith CA, Soares AS, Wierman JL, Zhu K, O'Brien P, Jura N, Ashworth A, Irwin JJ, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I. Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking. Sci Adv. 2021 04; 7(16).  View on PubMed
  13. Fontaine SD, Ashley GW, Houghton PJ, Kurmasheva RT, Diolaiti M, Ashworth A, Peer CJ, Nguyen R, Figg WD, Beckford-Vera DR, Santi DV. A Very Long-Acting PARP Inhibitor Suppresses Cancer Cell Growth in DNA Repair-Deficient Tumor Models. Cancer Res. 2021 02 15; 81(4):1076-1086.  View on PubMed
  14. Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, Young ID, Martins LC, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT, QCRG Structural Biology Consortium, Aimon A, Bennett JM, Neto JB, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs M, Gorrie-Stone TJ, Holton JM, Johnson MG, Krojer T, Meigs G, Powell AJ, Johannes Gregor Matthias Rack, Rangel VL, Russi S, Skyner RE, Smith CA, Soares AS, Wierman JL, Zhu K, Jura N, Ashworth A, Irwin J, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I. Fragment Binding to the Nsp3 Macrodomain of SARS-CoV-2 Identified Through Crystallographic Screening and Computational Docking. bioRxiv. 2020 Nov 24.  View on PubMed
  15. Guler GD, Ning Y, Ku CJ, Phillips T, McCarthy E, Ellison CK, Bergamaschi A, Collin F, Lloyd P, Scott A, Antoine M, Wang W, Chau K, Ashworth A, Quake SR, Levy S. Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA. Nat Commun. 2020 10 19; 11(1):5270.  View on PubMed
  16. Dreyer SB, Upstill-Goddard R, Paulus-Hock V, Paris C, Lampraki EM, Dray E, Serrels B, Caligiuri G, Rebus S, Plenker D, Galluzzo Z, Brunton H, Cunningham R, Tesson M, Nourse C, Bailey UM, Jones M, Moran-Jones K, Wright DW, Duthie F, Oien K, Evers L, McKay CJ, McGregor GA, Gulati A, Brough R, Bajrami I, Pettitt S, Dziubinski ML, Candido J, Balkwill F, Barry ST, Grützmann R, Rahib L, Glasgow Precision Oncology Laboratory,, Australian Pancreatic Cancer Genome Initiative, Johns A, Pajic M, Froeling FEM, Beer P, Musgrove EA, Petersen GM, Ashworth A, Frame MC, Crawford HC, Simeone DM, Lord C, Mukhopadhyay D, Pilarsky C, Tuveson DA, Cooke SL, Jamieson NB, Morton JP, Sansom OJ, Bailey PJ, Biankin AV, Chang DK. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer. Gastroenterology. 2021 01; 160(1):362-377.e13.  View on PubMed
  17. Chen WS, Haynes WA, Waitz R, Kamath K, Vega-Crespo A, Shrestha R, Zhang M, Foye A, Baselga Carretero I, Perez Garcilazo I, Zhang M, Zhao SG, Sjöström M, Quigley DA, Chou J, Beer TM, Rettig M, Gleave M, Evans CP, Lara P, Chi KN, Reiter RE, Alumkal JJ, Ashworth A, Aggarwal R, Small EJ, Daugherty PS, Ribas A, Oh DY, Shon JC, Feng FY. Autoantibody Landscape in Patients with Advanced Prostate Cancer. Clin Cancer Res. 2020 12 01; 26(23):6204-6214.  View on PubMed
  18. Dall GV, Vieusseux J, Seyed-Razavi Y, Godde N, Ludford-Menting M, Russell SM, Ashworth A, Anderson RL, Risbridger GP, Shackleton M, Britt KL. Parity reduces mammary repopulating activity but does not affect mammary stem cells defined as CD24?+?CD29/CD49fhi in mice. Breast Cancer Res Treat. 2020 Oct; 183(3):565-575.  View on PubMed
  19. Zhao SG, Chen WS, Li H, Foye A, Zhang M, Sjöström M, Aggarwal R, Playdle D, Liao A, Alumkal JJ, Das R, Chou J, Hua JT, Barnard TJ, Bailey AM, Chow ED, Perry MD, Dang HX, Yang R, Moussavi-Baygi R, Zhang L, Alshalalfa M, Laura Chang S, Houlahan KE, Shiah YJ, Beer TM, Thomas G, Chi KN, Gleave M, Zoubeidi A, Reiter RE, Rettig MB, Witte O, Yvonne Kim M, Fong L, Spratt DE, Morgan TM, Bose R, Huang FW, Li H, Chesner L, Shenoy T, Goodarzi H, Asangani IA, Sandhu S, Lang JM, Mahajan NP, Lara PN, Evans CP, Febbo P, Batzoglou S, Knudsen KE, He HH, Huang J, Zwart W, Costello JF, Luo J, Tomlins SA, Wyatt AW, Dehm SM, Ashworth A, Gilbert LA, Boutros PC, Farh K, Chinnaiyan AM, Maher CA, Small EJ, Quigley DA, Feng FY. The DNA methylation landscape of advanced prostate cancer. Nat Genet. 2020 08; 52(8):778-789.  View on PubMed
  20. Sachdeva A, Gouge J, Kontovounisios C, Nikolaou S, Ashworth A, Lim K, Chong I. Klotho and the Treatment of Human Malignancies. Cancers (Basel). 2020 Jun 23; 12(6).  View on PubMed

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