Michele Carbone, MD, PhD
- Researcher (Professor) and Full Member
Cancer Biology Program
- Director, Thoracic Oncology
University of Hawaii Cancer Center
- 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
- 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
- Mesothelioma Applied Research Foundation-Pioneer Award for
work on Mesothelioma, 2014
My research stems from the observation that only a fraction (5% or less) of those exposed to asbestos develop mesothelioma and that not all mesothelioma is related to asbestos exposure. I have studied mechanisms of asbestos carcinogenesis and have uncovered the role of SV40, of genetics and of erionite as co-factors in mesothelioma. By studying, over about 14 years, an epidemic of mesothelioma in Cappadocia, Turkey, together with Drs. I.Y. Baris and others, I formulated the hypothesis that the cause was gene x environment interaction (Roushdy-Hammady I, et al, The Lancet, 2001; Carbone M, et al, Nature Rev Cancer, 2007). With support of a NCI-PO1 (M. Carbone, PI) we began to search for a possible "mesothelioma gene" in U.S. families with high incidences of mesothelioma. Finally we identified the gene, BAP1, that when mutated causes an epidemic of mesothelioma in certain families (Testa JR, el al, Nature Genetics, 2011; Carbone M, et al, Nat Rev Cancer, 2013). Specifically, we discovered a new cancer syndrome characterized by the development of mesothelioma, uveal melanoma, and other cancers. Mesothelioma predominates upon exposure to asbestos or erionite (Carbone M, et al, JTM, 2022). We found that mesotheliomas and other malignancies that develop in carriers of germline BAP1 mutations have a much better prognosis than those that occur sporadically (Baumann F, et al, Carcinogenesis, 2015). More recently, we found that BAP1 plays a critical role in the pathogenesis of over 60% of sporadic mesotheliomas (Nasu M, et al, JTO, 2015), that germline mutations of BAP1 lower the minimal threshold exposure to asbestos required to cause mesothelioma in mice (Napolitano A, et al, Oncogene, 2015), and that several U.S. families carrying the same germline BAP1 mutations descend from a couple that immigrated to the U.S. from Germany in the early 1700s. This allowed us to identify novel branches of the family carrying the mutations and implement preventive strategies (Carbone M, et al, PLOS, Genetics, 2015).
In parallel studies we have uncovered significant erionite exposure in North Dakota, where we discovered concentrations of erionite in cars and school buses transiting on erionite gravel-paved roads as high as in the Cappadocian villages (Carbone M, et al, PNAS, 2011; Maher B, Nature, 468:884-885, Dec. 2010). Following our discovery and meetings with the ND state government, all or at least most "erionite roads" in ND were repaved with erionite-free gravel. This measure has likely saved many lives because after our discovery there has been the rapid development of the "fracking" industry to extract oil and gas in ND. The ND authorities estimate that presently over 50,000 trucks transit each day on roads that had been paved with erionite. Subsequently, we uncovered environmental exposure to asbestos in Nevada that we linked to a high incidence of mesothelioma among young adults (Baumann F, et al, JTO, 2015). This work received national press coverage (see D. Blum, New York Times, Feb. 10, 2015, pages D1-D4). Mainly because of our research, the NCI, and the IASLC sponsored an "International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers" at the University of Hawaii Cancer Center on November 9-10, 2015 that I organized and chaired. A consensus manuscript of this conference is under review.
In collaboration with H. Yang we have uncovered and are studying the role of HMGB1 in promoting mesothelioma growth (Yang H, et al, PNAS, 2006 and 2010; Carbone and Yang, Clinical Cancer Res, 2012; Jube S, et al, Cancer Res, 2012; Qi F, et al., AM J Pathol, 2013; Yang H, et al, CDD, 2015). Most recently Dr. Yang and I discovered that specific isoforms of HMGB1 allow identification of individuals exposed to asbestos and among them other HMGB1 isoforms single out those who have developed mesothelioma (Napolitano A, et al, Clinical Cancer Res, in press). A clinical trial sponsored by the NCI to validate these very exciting findings will start in 2016 led by Drs. Yang and our long-time collaborator Dr. H.I. Pass, with whom I have had the pleasure and fortune to work for over 20 years. I am a strong proponent of multidisciplinary collaborative team research. Our research has been characterized by laboratory research, fieldwork and by teamwork. In 2008, as PI, I received the first AACR-Landon Innovator Award for International Collaboration in Cancer Research. Our research team includes scientists from multiple countries who specialize in different disciplines including pathology, surgery, genetics, molecular biology, geology and mineralogy, and public health.
Clinical: I am board-certified in Anatomic Pathology (both in Italy and the U.S.) and specialize in pleural pathology and mesothelioma.
(for a complete CV and to read the publications see: http://www.oakparkpathology.com/About)
- Napolitano, A, Pellegrini L, Dey A, Larson D, Tanji M, Flores EG, Kendrick B, Lapid D, Powers A, Kanodia S, Pastorino S, Pass HI, Dixit V, Yang H, Carbone M. (2016). Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma. Oncogene, 35:1996-2002.
- Yoshikawa Y, Emi M, Hashimoto-Tamahoki T, Ohmuraya M, Sato A, Tsujimura T, Hasegawa S, Nakano T, Nasu M, Pastorino S, Szymiczek A, Bononi A, Tanji M, Pagano I, Gaudino G, Napolitano A, Goparajiu C, Pass HI, Yang H, Carbone M. (2016). High-density array-CGH with targeted NGS unmask multiple non-contiguous minute deletions on chromosome 3p21 in mesothelioma. Proc Natl Aca Sci USA, 113:13432-13437.
- Mao W, Zhang X, Guo Z, Gao Z, Pass HI, Yang H, Carbone M. (2016). Mesothelioma in Eastern China is Mostly Prevalent Among Young Women. JAMA Oncol, Dec 1. doi: 10.1001/jamaoncol.2016.5487, advance online publ.
- Carbone M, Kanodia S, Chao A, Miller A, Wali A, Weissman D, Adjei A, Baumann F. Boffetta P, Buck B, dePerrot M, Dogan AU, Gavett S, Gualtieri A, Hassan R, Hesdorffer M, Hirsch FR, Larson D, Mao W, Masten S, Pass HI, Peto J, Pira E, Steele I, Tsao A, Woodard GA, Malik S. (2016). Consensus Report of the 2015 Weinman International Conference on Mesothelioma. J Thorac Oncol, 16 Aug;11(8):1246-62. doi: 10.1016/j.jtho.2016.04.028.
- Yang H, Pellegrini L, Napolitano A, Giorgi C, Jube S, Preti A, Jennings CJ, De Marchis F, Flores EG, Larson D, Pagano I, Tanji M, Powers A, Kanodia S, Gaudino G, Pastorino S, Pass HI, Pinton P, Bianchi ME, Carbone M. (2015). Aspirin delays mesothelioma growth by inhibiting HMGB1-mediated tumor progression. Cell Death Dis, 6:e1786.
- Baumann F, Flores E, Napolitano A, Kanodia A, Taioli E, Pass H, Yang H, Carbone M. (2015). Mesothelioma Patients with Germline BAP1 Mutations Have Seven-Fold Improved Long-term Survival. Carcinogenesis, 36:76-81.
- Baumann F, Buck BJ, Metcalf RV, McLaurin BT, Merkler DJ, Carbone M. (2015). The Presence of Asbestos in the Natural Environment is Likely Related to Mesothelioma in Young Individuals and Women from Southern Nevada. J Thorac Oncol, 10(5):731-7. PMCID: PMC4406807.
- Carbone M, Flores EG, Emi M, Johnson TA, Tsunoda T, Behner D, Hoffman H, Hesdorffer M, Nasu M, Napolitano A, Power A, Minaai M, Baumann F, Bryant-Greenwood P, Lauk O, Kirschner MB, Weder W, Opitz I, Pass HI, Gaudino G, Pastorino S, Yang H. (2015). Combined genetic and genealogic studies uncover a large BAP1 cancer syndrome kindred, tracing back nine generations to a common ancestor from the 1700s. PLoS Genet, 11(12): e1005633.
- Nasu M, Tanji M, Pastorino S, Flores E, Baumann F, Powers A, Kanodia S, Gaudino G, Yang H, Pass HI, Emi M and Carbone M. (2015). High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. J Thorac Oncol, 10(4):565-76. PMCID: PMC4408084.
- Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. (2013). Bap1 and cancer. Nat Rev Cancer, 13:153-159. PMCID: PMC3792854.
- Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M. (2011). Germline BAP1 mutations predispose to malignant mesothelioma. Nat Gen, 43(10):1022-1025. PMCID: PMC3184199.
Publication list via PubMed
- M. Carbone, Co-I, H.I. Pass & H. Yang, Co-PIs
"The EDRN Mesothelioma Biomarker Discovery Laboratory"
Determine the ability of serum mesothelin, serum HMGB1, and the combination of these two biomarkers as a diagnostic, pre-diagnostic as well as prognostic tool for MPM.
- M. Carbone, PI
"Germline BAP1 Mutations and Malignant Mesothelioma: Mechanisms and Early Detection"
The proposed studies will determine how BAP1 mutations increase susceptibility to MM and evaluate whether HMGB1 can be used as a biomarker for early detection of malignant mesothelioma in this high risk cohort.
- M. Carbone, S. Kanodia, T. Mak, H.I. Pass, H. Yang, Co-PIs
DoD Peer Reviewed Cancer Research Program Translational Team Science Award
"HMGB1 and Its Isoforms As Biomarkers For Mineral Fiber Exposure and MM Detection"
Our proposed studies will significantly enhance our knowledge of how mesothelioma develops, elucidate which isoform of HMGB1 is required at what stages of disease, and prospectively evaluate HMGB1 and its isoforms as a novel biomarker to distinguish between asbestos exposure and malignant mesothelioma.
07/01/16 â€“ 06/30/19
- M. Carbone & H. Yang, Co-PIs
DoD Peer Reviewed Cancer Research Program Idea Award with Special Focus
"Identification and validation of novel germline DNA variants associated to increased risk of malignant mesothelioma"
The objective of our research is to identify which are these genetic modifications that confer higher risk of developing mesothelioma. Identifying, among the millions of individuals exposed to asbestos (many belonging to the military), those at higher risk of mesothelioma, will allow us to implement personalized programs of screening and early detection and treatment of mesothelioma for these individuals.
Philanthropy: Support from the University of Hawaii Foundation that received unrestricted donations to support my mesothelioma research from Riviera United-4-a Cure Foundation, and from Honeywell International Inc.