Rosemary J. Akhurst, PhD

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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

rakhurst@cc.ucsf.edu

Phone: (415) 514-0215 (voice)
Box 0128, UCSF
San Francisco, CA 94143-0128

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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.

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
 


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. 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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  2. Matters of context guide future research in TGFß superfamily signaling. Sci Signal. 2015; 8(399):re10.
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  3. 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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  4. 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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  5. 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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  6. BMP-9 balances endothelial cell fate. Proc Natl Acad Sci U S A. 2013 Nov 19; 110(47):18746-7.
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  7. 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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  8. 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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  9. Targeting the TGFß signalling pathway in disease. Nat Rev Drug Discov. 2012 Oct; 11(10):790-811.
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  10. The paradoxical TGF-ß vasculopathies. Nat Genet. 2012 Aug; 44(8):838-9.
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  11. Complexities of TGF-ß targeted cancer therapy. Int J Biol Sci. 2012; 8(7):964-78.
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  12. TGF-ß-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion. J Cell Sci. 2012 Mar 1; 125(Pt 5):1259-73.
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  13. Defective retinal vascular endothelial cell development as a consequence of impaired integrin aVß8-mediated activation of transforming growth factor-ß. J Neurosci. 2012 Jan 25; 32(4):1197-206.
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  14. Mouse and human strategies identify PTPN14 as a modifier of angiogenesis and hereditary haemorrhagic telangiectasia. Nat Commun. 2012; 3:616.
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  15. The complexities of TGF-ß action during mammary and squamous cell carcinogenesis. Curr Pharm Biotechnol. 2011 Dec; 12(12):2138-49.
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  16. TGFß1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo. Clin Cancer Res. 2011 Nov 1; 17(21):6754-65.
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  17. Outgrowth of drug-resistant carcinomas expressing markers of tumor aggression after long-term TßRI/II kinase inhibition with LY2109761. Cancer Res. 2011 Mar 15; 71(6):2339-49.
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  18. Taking thalidomide out of rehab. Nat Med. 2010 Apr; 16(4):370-2.
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  19. Elevated cutaneous Smad activation associates with enhanced skin tumor susceptibility in organ transplant recipients. Clin Cancer Res. 2009 Aug 15; 15(16):5101-7.
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  20. Transforming growth factor-beta in breast cancer: too much, too late. Breast Cancer Res. 2009; 11(1):202.
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