V. Courtney Broaddus, MD

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

Professor, Department of Medicine; Associate Director, Lung Biology Center, UCSF

CBroaddus@medsfgh.ucsf.edu

Phone: (415) 206-3513 (voice)
Box 0854, UCSF
San Francisco, CA 94143-0854

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Cancer Center Membership

Program Member » Cancer, Immunity, and Microenvironment

Research Summary

After an early career investigating the biology of the pleural mesothelial cell, I have worked for the last 10 years to understand the mechanisms of the chemoresistance of the pleural tumor, mesothelioma. In tackling this question, I have pursued innovative models, mainly 3D in vitro and ex vivo mesothelioma models, and shown how they provide clinically relevant insights into mesothelioma chemoresistance. I have established valuable collaborations with mesothelioma surgeon Dr. Raphael Bueno and his colleague Dr. Bill Richards, providing access to fresh tumor tissue, tissue microarrays and extensive clinical outcome data. After multiple studies on apoptotic signaling in mesothelioma, Dr. Barbone and I realized that many of our findings were more consistent with a role for autophagy, a recycling mechanism involved in cell death and survival. After recruiting Dr. Carlo Follo to my lab, we pursued the subject of autophagy with increasing excitement. It has become clear that autophagy in mesothelioma is best studied in 3D, that both mesothelioma cell lines in 3D and mesothelioma tumors can be divided into those that have either an active autophagy or have little autophagy at baseline, and that a marker of autophagy initiation correlates with survival in patients with mesothelioma and is independent of other known prognostic factors, including histology. With these tools, collaborations, dedication, and experience, I will carry out this research plan into the role of autophagy in mesothelioma, with hopes for finding new insights into mesothelioma biology and therapeutic vulnerability.

Education

Duke University, Durham, North Carolina, B.S., Summa Cum Laude, 1975, Zoology
University of Pennsylvania, Philadelphia, PA, M.D., 1979, Medicine
University of Pennsylvania, Philadelphia, PA, Intern and Resident, 1979-82, Internal Medicine
University of California San Francisco, CA, Fellow, 1983-84, Pulmonary Disease


Professional Experience

  • 1986-88
    Instructor in Medicine, University of California, San Francisco, CA
  • 1988-1995
    Assistant Professor in Medicine, University of California, San Francisco, CA
  • 1991-present
    Member, Lung Biology Center, University of California, San Francisco, CA
  • 1995-2001
    Associate Professor in Medicine, University of California, San Francisco, CA
  • 1998-present
    Chief, Division of Pulmonary and Critical Care, University of California, San Francisco, CA
  • 2001-present
    Professor in Medicine, University of California, San Francisco, CA
  • 2001-2002
    Visiting Scientist, Comprehensive Cancer Center, Dr. Gerard Evan's Laboratory
  • 2004-present
    Associate Director, Lung Biology Center, Univ. of Calif., San Francisco

Honors & Awards

  • 1978
    Alpha Omega Alpha, University of Pennsylvania
  • 1979
    Janet M. Glasgow Memorial Award and Citation for Outstanding Female Medical Student
  • 1987-1992
    Clinical Investigator Award, NHLBI
  • 1988
    American Physiological Society (elected)
  • 1991
    Associate, Scientific Staff, Cardiovascular Research Institute, UCSF (elected)
  • 1991
    Distinction in Teaching Award, University of California, San Francisco, CA
  • 1992
    Pretenure Award, University of California, San Francisco, CA
  • 1998-2001
    UC Tobacco Related Disease Program Award for "Programmed Cell Death in Cigarette- Induced Lung Disease"
  • 1999-2002
    President, International Mesothelioma Interest Group

Selected Publications

  1. Autophagy Correlates with the Therapeutic Responsiveness of Malignant Pleural Mesothelioma in 3D Models. PLoS One. 2015; 10(8):e0134825.
    View on PubMed
  2. Medical Subspecialty Textbooks in the 21st Century. Essential or Headed for Extinction? Ann Am Thorac Soc. 2015 Aug; 12(8):1113-5.
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  3. Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells. Lung. 2015 Oct; 193(5):831-7.
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  4. Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors. Cell Death Dis. 2015; 6:e1757.
    View on PubMed
  5. BAK and NOXA are critical determinants of mitochondrial apoptosis induced by bortezomib in mesothelioma. PLoS One. 2013; 8(6):e65489.
    View on PubMed
  6. Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression. PLoS One. 2012; 7(12):e52753.
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  7. Ligation of CM1 enhances apoptosis of lung cancer cells through different mechanisms in conformity with EGFR mutation. Int J Oncol. 2013 Feb; 42(2):469-77.
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  8. Vorinostat/SAHA-induced apoptosis in malignant mesothelioma is FLIP/caspase 8-dependent and HR23B-independent. Eur J Cancer. 2012 May; 48(7):1096-107.
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  9. Rapid generation of in vitro multicellular spheroids for the study of monoclonal antibody therapy. J Cancer. 2011; 2:507-14.
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  10. The Bcl-2 repertoire of mesothelioma spheroids underlies acquired apoptotic multicellular resistance. Cell Death Dis. 2011; 2:e174.
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  11. Novel human single chain antibody fragments that are rapidly internalizing effectively target epithelioid and sarcomatoid mesotheliomas. Cancer Res. 2011 Apr 1; 71(7):2428-32.
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  12. The development and characterization of a human mesothelioma in vitro 3D model to investigate immunotoxin therapy. PLoS One. 2011; 6(1):e14640.
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  13. Non-neoplastic and neoplastic pleural endpoints following fiber exposure. J Toxicol Environ Health B Crit Rev. 2011; 14(1-4):153-78.
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  14. Identification of MCAM/CD146 as the target antigen of a human monoclonal antibody that recognizes both epithelioid and sarcomatoid types of mesothelioma. Cancer Res. 2009 Feb 15; 69(4):1570-7.
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  15. Bcl-2 family proteins contribute to apoptotic resistance in lung cancer multicellular spheroids. Am J Respir Cell Mol Biol. 2009 Jul; 41(1):14-23.
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  16. mTOR mediates survival signals in malignant mesothelioma grown as tumor fragment spheroids. Am J Respir Cell Mol Biol. 2008 Nov; 39(5):576-83.
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  17. Mammalian target of rapamycin contributes to the acquired apoptotic resistance of human mesothelioma multicellular spheroids. J Biol Chem. 2008 May 9; 283(19):13021-30.
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  18. Targeted drug delivery to mesothelioma cells using functionally selected internalizing human single-chain antibodies. Mol Cancer Ther. 2008 Mar; 7(3):569-78.
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  19. Anti-mesothelin immunotoxin SS1P in combination with gemcitabine results in increased activity against mesothelin-expressing tumor xenografts. Clin Cancer Res. 2007 Dec 1; 13(23):7166-71.
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  20. Squamous metaplasia amplifies pathologic epithelial-mesenchymal interactions in COPD patients. J Clin Invest. 2007 Nov; 117(11):3551-62.
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