Research Summary

I am a UCSF Professor of Anatomy in the Helen Diller Family Comprehensive Cancer Center in San Francisco. My laboratory has for many years studied the role of TGFβ signaling in cancer, development, and vascular biology. We primarily study chemically-induced carcinomas, namely DMBA/TPA-induced cutaneous squamous cell carcinomas that are heterogenous and share many genetic features with human cancers. Our studies were the first to show that TGFβ1 is induced by tumor promotion and can play both positive and negative roles in tumor initiation and progression in vivo. We have shown that this growth factor is important in cancer stem cell maintenance, and a major regulator of the tumor microenvironment including angiogenesis and potent immune-suppression, all activities that drive tumor metastasis. Currently, we undertake translational studies investigating how targeting of distinct TGFβ signaling components can be used therapeutically, particularly to augment immunotherapy, and our studies have contributed to the initiation of ongoing clinical trials of novel anti-TGFβ signaling agents by Novartis and Pfizer. We also use mouse models to investigate how germline variants influence responses to immunotherapy, particularly through effects on tumor immunity and the tumor microenvironment. Additionally, we have a strong interest in the cellular and molecular mechanisms driving abnormal vascular biology in the human genetic disorder Hereditary Hemorrhagic Telangiectasia, that results from loss of function mutations in genes encoding TGFβ/BMP signaling molecules, endoglin, ACVRL1/Alk1, or Smad4, and the influence of germline genetic variants on HHT disease progression. Our studies often involve large collaborative teams.

As Faculty Director of the NCI-sponsored CCSG Preclinical Therapeutics Core (PTC), my interest is 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. Through competitive federal and non-federal awards, we have acquired instrumentation for all three UCSF cancer campuses. These include Vevo770 and Vevo2100 ultrasound imaging platforms, several IVIS Spectrum multichannel fluorescent/ bioluminescent imagers, an Xstrahl small animal micro-CT-guided irradiator, and a high-resolution high through put micro-CT scanner.

Research Funding

  • January 1, 2018 - December 31, 2020 - Advancing the translatability of mouse models for cancer immunotherapy, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA210561
  • August 1, 2019 - July 31, 2020 - PerkinElmer Quantum GX CT-imager, Principal Investigator. Sponsor: NIH, Sponsor Award ID: S10OD025022
  • September 1, 2015 - May 31, 2019 - Circulating cells as tools to study vascular pathobiology of HHT, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: R01HL122869
  • September 15, 2014 - August 31, 2015 - Circulating cells as tools to study vascular pathobiology of HHT, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: R56HL122869

Education

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

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
    • 2019-current
    Vice-Chair Global Research and Medical Advisory Board of CureHHT
  • 2020
    UCSF Biomedical Sciences (BMS) Program Mentoring Award

Selected Publications

  1. Derynck R, Turley SJ, Akhurst RJ TGFß biology in cancer progression and immunotherapy.  View on PubMed
  2. 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.  View on PubMed
  3. 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.  View on PubMed
  4. Budi EH, Mamai O, Hoffman S, Akhurst RJ, Derynck R Enhanced TGF-ß Signaling Contributes to the Insulin-Induced Angiogenic Responses of Endothelial Cells.  View on PubMed
  5. Mamai O, Dodagatta-Marri E, Akhurst RJ From prevention to cure, repurposing anti-viral vaccines for cancer immunotherapy.  View on PubMed
  6. 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.  View on PubMed
  7. Akhurst RJ Targeting TGF-ß Signaling for Therapeutic Gain.  View on PubMed
  8. 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.  View on PubMed
  9. 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.  View on PubMed
  10. Akhurst RJ, Padgett RW Matters of context guide future research in TGFß superfamily signaling.  View on PubMed
  11. 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.  View on PubMed
  12. 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.  View on PubMed
  13. 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.  View on PubMed
  14. Derynck R, Akhurst RJ BMP-9 balances endothelial cell fate.  View on PubMed
  15. 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.  View on PubMed
  16. Rosemary J. Akhurst, Akiko Hata Erratum: Targeting the TGFß signalling pathway in disease.  View on PubMed
  17. 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.  View on PubMed
  18. Akhurst RJ, Hata A Targeting the TGFß signalling pathway in disease.  View on PubMed
  19. Akhurst RJ The paradoxical TGF-ß vasculopathies.  View on PubMed
  20. Connolly EC, Freimuth J, Akhurst RJ Complexities of TGF-ß targeted cancer therapy.  View on PubMed

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