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Faculty

Michele Carbone, MD, PhD

Michele Carbone, MD, PhD
  • Center Director
  • Professor of Pathology
    University of Hawaii Cancer Center

Degrees

  • 1984 MD, Medical School of Rome "La Sapienza", Italy
  • 1993 PhD, Medical School of Rome "La Sapienza", Italy
    • Medical Board Certifications in Anatomic Pathology:
      1988 University of Rome, Italy,
      1999 University of Chicago, USA

    Honors

    • National Institutes of Health Fogarty Fellowship, 1986-1994
    • Knight of the Republic of Italy (Cavaliere della Repubblica), 2001
    • Landon Foundation-American Association for Cancer Research INNOVATOR Award for International Collaboration in Cancer Research, 2008
    • American Cancer Society Board of Directors, 2011

Research Focus

Dr. Michele Carbone leads a multi-disciplinary, international team of scientists in the study of mesothelioma, an aggressive cancer affecting the mesothelial lining of the lungs and internal chest wall. This deadly cancer, linked with exposure to mineral fibers such as asbestos and erionite, is difficult diagnose at early stages. Late stage mesothelioma is resistant to treatment. As the global use of asbestos and other mineral fibers, continue to rise, the development of improved diagnostic tools and therapies for mesothelioma requires critical attention.

Dr. Carbone and his team have demonstrated that mineral fibers and viruses are co-carcinogens in the transformation of human mesothelial cells into cancer cells. They found that SV40, a DNA tumor virus found in contaminated human polio vaccines, causes mesothelioma in animals, causes malignant transformation of human mesothelial cells in tissue culture and is present in some mesothelioma biopsies. Dr. Carbone's work has elucidated the molecular mechanisms that lead from SV40 infection to the formation of mesothelioma.

The manner by which mineral fiber exposure leads to mesothelioma has remained obscure for many years. Asbestos fibers damage and kill mesothelial cells that they come in contact with. So, how could these cells survive to become cancer cells? Dr. Carbone and Dr. Yang have recently found that asbestos exposure triggers the secretion of HMGB1 and TNF-α that make mesothelial cells somewhat resistant to asbestos toxicity; asbestos-genetically damaged mesothelial cells may therefore survive and become cancer cells. A clinical trial is currently being developed to test drugs that block the effects of HMGB1 and TNF-α in a high-risk mesothelioma population. Dr. Carbone's team has also identified new biomarkers of early stage mesothelioma, which are currently being tested for their usefulness in clinical applications.

Since 1997, Dr. Carbone has conducted research in Cappadocia, Turkey, where a devastating mesothelioma epidemic has been killing over half the population due to erionite exposure. Dr. Carbone's work led the Turkish Ministry of Health to build two erionite-free villages that will greatly reduce the risk of mesothelioma in this area.  The studies in Cappadocia revealed genetic susceptibility in certain families to this malignancy. Recently, Dr. Carbone and his team discovered that families which carry germline mutations in the BAP1 gene are affected by mesothelioma, uveal melanoma and possibly other cancers. The possibility of using genetic testing for BAP1 mutations to identify individuals at high risk for mesothelioma is currently being investigated.

Dr. Carbone and his team have recently discovered high levels of erionite in the gravel used to pave more than 300 miles of roads in North Dakota. The people living in these parts of the country have exposure to eriontie similar to those found in some villages in Cappadocia. This finding has led to EPA intervention and preventive measures are being adopted to reduce exposure and screen cohorts at risk of mesothelioma.

Publications

  • Carbone M, Emri S, Dogan U, Steele I, Tuncer M, Pass HI, Baris YI.  A mesothelioma epidemic in Cappadocia:  scientific developments and unexpected social outcomes.  Nature Reviews Cancer, 7:147-154, 2007.
  • Yang H, Rivera Z, Jube S, Nasu M, Bertino P, Goparaju C, Franzoso G, Lotze MT, Krausz T, Pass HI, Bianchi ME, Carbone M.  Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation.  Proc Natl Acad Sci USA, 107: 12611-12616, 2010.  PMCID: PMC2906549.
  • Carbone M, Baris YI, Bertino P, Brass B, Comertpay S, Dogan AU, Gaudino G, Jube S, Kanodia S, Partridge CR, Pass HI, Rivera ZS, Steele I, Tuncer M, Way S, Yang H, Miller A.  Erionite exposure in North Dakota and Turkish villages with mesothelioma.  Proc Natl Acad Sci USA, 108:13618-23, 2011.
  • Carbone M, Ly BH, Dodson RF, Pagano I, Morris PT, Dogan UA, Gazdar AF, Pass HI, Yang H. Malignant mesothelioma: Facts, myths and hypotheses.  J Cell Physiol, 2011 Mar 16; doi: 10.1002/jcp.22724.  [Epub ahead of print].  PMCID:  PMC3143206.
  • Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox N, Dogan AU, Pass, HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M. Germline BAP1 mutations predispose to malignant mesothelioma.  Nat Genet, Aug 28 2011; doi:10.1038/ng.912.  [Epub ahead of print]

Publication list via PubMed

Active Grants

  • M. Carbone, Principal Investigator
    R01 CA106567/ NCI
    "Role of Cell Mediators in Asbestos-SV40 Carcinogenesis"
    March 8, 2005-February 28, 2010
  • M. Carbone, Principal Investigator
    1P01 CA114047-01A1/ NCI
    "Pathogenesis of Mesothelioma"
    September 15, 2006-August 31, 2011
  • M. Carbone, Principal Investigator
    AACR 08-60-27
    Landon Foundation-AACR Innovator Award for International Collaboration in Cancer Research
    "Gene Environment Interaction and Early Detection of Mesothelioma in Cappadocia, Turkey"
    July 1, 2008-June 30, 2010
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