University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Rosemary J. Akhurst, PhD

Rosemary J. Akhurst, PhD

Professor In Residence, Helen Diller Family Comprehensive Cancer Center and Department of Anatomy, UCSF; Director, Preclinical Therapeutics Core Facility, Helen Diller Family Comprehensive Cancer Center, UCSF

Cancer Center Program Memberships

Cancer Genetics

Research Summary

I am a PhD scientist and professor within the HDFCCC, with over twenty-five years of experience working with mouse models of cancer, focusing on the TGFβ signaling pathway. We have shown that TGFβ is a major player in tumor progression, cancer stem cell maintenance, and a major regulator of tumor microenvironment including angiogenesis and potent immune-suppression, all activities that drive tumor metastasis. Most recently, we began investigations into interactions between TGFβ blockade and immune checkpoint blockade. We use primary chemically induced carcinomas, namely DMBA/TPA-induced cutaneous SCC and urethane-induced lung adenocarcinoma, to investigate cellular and molecular mechanisms of complementation between TGFβ blockade and immune checkpoint inhibitors in tumor rejection. In collaboration with the Derynck lab, we also investigate detailed molecular mechanisms regulating TGFβ-driven EMT in cancer. We also have a strong interest in cellular and molecular mechanisms driving abnormal angiogenesis in the human genetic disorder HHT, which is caused by functional loss of a single allele of one of the genes encoding TGFβ/BMP signaling molecules, endoglin, ACVRL1/Alk1, or Smad4. We are currently investigating circulating stem cells and immune cells from HHT patients to provide deeper molecular insight into altered cellular properties and signaling pathways in human HHT.
As Faculty Director of the NCI-sponsored CCSG Preclinical Therapeutics Core (PTC), I have a strong interest in providing access to state of the art technology and technical support for small animal cancer therapeutics and imaging for members of the HDFCCC scientific community and beyond. Since my tenure as Director of the PTC, through federal and non-federal awards, we have acquired instrumentation for all three UCSF cancer campuses. This includes Vevo770 and Vevo2100 ultrasound imaging platforms, two IVIS Spectrum multichannel fluorescent/ bioluminescent imagers, two IVIS 100 imagers, and a Leica fluorescence dissecting microscope. We also have successful and pending awards for a SAARP CT-guided irradiator.


Imperial College of Science and Technology, University of London, UK, BSc (Hons), 1st class, 1975-1978, Biochemistry
Beatson Institute for Cancer Research, Glasgow, UK, PhD, 1978-1981, Molecular Biology

Professional Experience

  • 1982-1984
    Post-doctoral fellow, California Institute of Technology, Pasadena, CA
  • 1984-1988
    Lecturer, Department of Biochemistry and Molecular Genetics, St. Mary's Hospital Medical School, London University, UK
  • 1988-1990
    Lecturer, Department of Medical Genetics, Glasgow University, UK
  • 1990-1992
    Senior Lecturer, Department of Medical Genetics, Glasgow University, UK
  • 1992-1996
    Reader, Department of Medical Genetics, Glasgow University, UK
  • 1997-1999
    Senior Scientist, Onyx Pharmaceuticals, Richmond, CA
  • 1999-2004
    Research Scientist, Cancer Research Institute, UCSF
  • 2004-2007
    Adjunct Professor, Dept of Anatomy and Cancer Research Institute, UCSF
  • 2007-present
    Professor In Residence, Dept of Anatomy and Cancer Research Institute, UCSF

Honors & Awards

  • 1975, 1976
    Imperial College Entrance Scholarship
  • 1978
    Ewart Stickings Award for Excellence in Biochemistry (Top Biochemistry Student, Imperial College, London)
  • 1978
    Associate of the Royal College of Science
  • 1982-4
    European Molecular Biology Organization (EMBO) Fellowship Award
  • 1984
    "New Blood" Lectureship, London University, UK
  • 2011-2017
    Charter Member NIH VCMB Study Section

Selected Publications

  1. Dodagatta-Marri E, Meyer DS, Reeves MQ, Paniagua R, To MD, Binnewies M, Broz ML, Mori H, Wu D, Adoumie M, Del Rosario R, Li O, Buchmann T, Liang B, Malato J, Arce Vargus F, Sheppard D, Hann BC, Mirza A, Quezada SA, Rosenblum MD, Krummel MF, Balmain A, Akhurst RJ. a-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by a-TGFß antibody to promote durable rejection and immunity in squamous cell carcinomas. J Immunother Cancer. 2019 03 04; 7(1):62.
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  2. Katsuno Y, Meyer DS, Zhang Z, Shokat KM, Akhurst RJ, Miyazono K, Derynck R. Chronic TGF-ß exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition. Sci Signal. 2019 02 26; 12(570).
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  3. Budi EH, Mamai O, Hoffman S, Akhurst RJ, Derynck R. Enhanced TGF-ß Signaling Contributes to the Insulin-Induced Angiogenic Responses of Endothelial Cells. iScience. 2019 Jan 25; 11:474-491.
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  4. Mamai O, Dodagatta-Marri E, Akhurst RJ. From prevention to cure, repurposing anti-viral vaccines for cancer immunotherapy. Biotarget. 2018 Dec; 2.
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  5. Du D, Katsuno Y, Meyer D, Budi EH, Chen SH, Koeppen H, Wang H, Akhurst RJ, Derynck R. Smad3-mediated recruitment of the methyltransferase SETDB1/ESET controls Snail1 expression and epithelial-mesenchymal transition. EMBO Rep. 2018 01; 19(1):135-155.
    View on PubMed
  6. Akhurst RJ. Targeting TGF-ß Signaling for Therapeutic Gain. Cold Spring Harb Perspect Biol. 2017 Oct 03; 9(10).
    View on PubMed
  7. Muthusamy BP, Budi EH, Katsuno Y, Lee MK, Smith SM, Mirza AM, Akhurst RJ, Derynck R. ShcA Protects against Epithelial-Mesenchymal Transition through Compartmentalized Inhibition of TGF-ß-Induced Smad Activation. PLoS Biol. 2015 Dec; 13(12):e1002325.
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  8. Megan Murnane, Eugen Dhimolea, Ruojing Li, Megan A. Bariteau, Diamond D. Wheeler, Rosemary J. Akhurst, Aaron C. Logan, Pamela Munster, Arun Wiita, Thomas G. Martin, Jeffrey L. Wolf, Jun O. Liu, Constantine S. Mitsiades, Blake T. Aftab. Defining Primary Marrow Microenvironment-Induced Synthetic Lethality and Resistance for 2,684 Approved Drugs Across Molecularly Distinct Forms of Multiple Myeloma. Blood. 2015 Dec 3; 126(23):503-503.
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  9. Akhurst RJ, Padgett RW. Matters of context guide future research in TGFß superfamily signaling. Sci Signal. 2015 Oct 20; 8(399):re10.
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  10. Letteboer TG, Benzinou M, Merrick CB, Quigley DA, Zhau K, Kim IJ, To MD, Jablons DM, van Amstel JK, Westermann CJ, Giraud S, Dupuis-Girod S, Lesca G, Berg JH, Balmain A, Akhurst RJ. Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14. Front Genet. 2015; 6:67.
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  11. Arnold TD, Niaudet C, Pang MF, Siegenthaler J, Gaengel K, Jung B, Ferrero GM, Mukouyama YS, Fuxe J, Akhurst R, Betsholtz C, Sheppard D, Reichardt LF. Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking aVß8-TGFß signaling in the brain. Development. 2014 Dec; 141(23):4489-99.
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  12. Kawasaki K, Freimuth J, Meyer DS, Lee MM, Tochimoto-Okamoto A, Benzinou M, Clermont FF, Wu G, Roy R, Letteboer TG, Ploos van Amstel JK, Giraud S, Dupuis-Girod S, Lesca G, Westermann CJ, Coffey RJ, Akhurst RJ. Genetic variants of Adam17 differentially regulate TGFß signaling to modify vascular pathology in mice and humans. Proc Natl Acad Sci U S A. 2014 May 27; 111(21):7723-8.
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  13. Derynck R, Akhurst RJ. BMP-9 balances endothelial cell fate. Proc Natl Acad Sci U S A. 2013 Nov 19; 110(47):18746-7.
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  14. Kang HC, Quigley DA, Kim IJ, Wakabayashi Y, Ferguson-Smith MA, D'Alessandro M, Birgitte Lane E, Akhurst RJ, Goudie DR, Balmain A. Multiple self-healing squamous epithelioma (MSSE): rare variants in an adjacent region of chromosome 9q22.3 to known TGFBR1 mutations suggest a digenic or multilocus etiology. J Invest Dermatol. 2013 Jul; 133(7):1907-10.
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  15. Rosemary J. Akhurst, Akiko Hata. Erratum: Targeting the TGFß signalling pathway in disease. Nature Reviews Drug Discovery. 2012 Nov 1; 11(11):886-886.
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  16. Freimuth J, Clermont FF, Huang X, DeSapio A, Tokuyasu TA, Sheppard D, Akhurst RJ. Epistatic interactions between Tgfb1 and genetic loci, Tgfbm2 and Tgfbm3, determine susceptibility to an asthmatic stimulus. Proc Natl Acad Sci U S A. 2012 Oct 30; 109(44):18042-7.
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  17. Akhurst RJ, Hata A. Targeting the TGFß signalling pathway in disease. Nat Rev Drug Discov. 2012 Oct; 11(10):790-811.
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  18. Akhurst RJ. The paradoxical TGF-ß vasculopathies. Nat Genet. 2012 Jul 27; 44(8):838-9.
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  19. Connolly EC, Freimuth J, Akhurst RJ. Complexities of TGF-ß targeted cancer therapy. Int J Biol Sci. 2012; 8(7):964-78.
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  20. S. Lamouille, E. Connolly, J. W. Smyth, R. J. Akhurst, R. Derynck. TGF- -induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion. Development. 2012 May 15; 139(10):e1008-e1008.
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