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
August 5, 1999 - May 31, 2023 - Cancer Center Support Grant , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P30CA082103
January 1, 2018 - December 31, 2021 - Advancing the translatability of mouse models for cancer immunotherapy , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA210561
September 1, 2015 - May 31, 2021 - Circulating cells as tools to study vascular pathobiology of HHT , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01HL122869
August 1, 2019 - July 31, 2020 - PerkinElmer Quantum GX CT-imager , Principal Investigator . Sponsor: NIH, Sponsor Award ID: S10OD025022
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