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.
- Napolitano A, Antoine DJ, Pellegrini L, Baumann F, Pagano IS, Pastorino S, Goparaju CM, Prokrym K, Canino C, Pass HI, Carbone M, Yang H. HMGB1 and its hyper-acetylated isoform are sensitive and specific serum biomarkers to detect asbestos exposure and to identify mesothelioma patients. Clin Cancer Res, In Press.
- 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 Genetics, Dec 18, 2015.
- 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, doi: 10.1038/cddis.2015.153.
- Napolitano, A, Pellegrini L, Dei 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. (2015). Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma. Oncogene, Advance online publication, June 29, 2015.
- Baumann F, Buck BJ, Metcalf RV, McLaurin BT, Merkler D, 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, 10:731-7.
- 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.
- Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Baumann F, Zhang YA, Gazdar A, Kanodia S, Tiirikainen M, Flores E, Gaudino G, Becich GJ, Pass HI, Yang H, Carbone M. (2015). High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. J Thorac Oncol, 10:565-76.
Publication list via PubMed
- M. Carboned, PI
"Germline BAP1 Mutations and Malignant Mesothelioma: Mechanisms and Early Detection"
07/01/15 - 06/30/20
- M. Carbone, Partnering PI; H. Yang, Initiating PI; Other Partnering PIs, H.I. Pass, T. Mak, S. Kanodia
CA150671P1DoD (Peer Reviewed Cancer Research Program â€“Translational Team Science Award)
"HMGB1 and Its Isoforms as Biomarkers for Mineral Fiber Exposure and MM Detection"
07/01/16 â€“ 06/30/19
$1.2 M (Total direct cost)
- M. Carbone, H. Yang, Co-PIs
"Identification and Validation of Novel Germline DNA Variants Associated to Increased Risk of Malignant Mesothelioma"
$616,000 (Total direct cost)
- M. Carbone, H. Yang, Co-PIs
"HMGB1, A Biomarker for Mineral Fiber Exposure and Detection of Malignant Mesothelioma"
10/31/12 - 10/30/16
- M. Carbone, PI
"Pathogenesis of Malignant Mesothelioma"
07/01/10 - Open