Michele Carbone, MD, PhD
Director, Thoracic Oncology, University of Hawaiʻi Cancer Center
Full Member, Cancer Biology Program, University of Hawaiʻi Cancer Center
Special Health and Science Advisor to Josh Green, Governor, State of Hawaiʻi
William & Ellen Melohn Chair in Cancer Biology
Academic Appointment(s):
Professor (Researcher), University of Hawaiʻi Cancer Center, University of Hawaiʻi at Mānoa
Professor, Department of Pathology, John A. Burns School of Medicine, University of Hawaiʻi at Mānoa
Degree(s):
MD, Medical School of Rome "La Sapienza", Italy
PhD, Medical School of Rome "La Sapienza", Italy
University of Rome, Italy - Medical Board Certifications in Anatomic Pathology
University of Chicago, USA - Medical Board Certifications in Anatomic Pathology
Honor(s)
2018 - The iMiG Wagner Medal, the highest honor presented by the iMiG to a leader in the field for "discovering the role of genetics in the pathogenesis of mesothelioma."
2018 - PAIR (Prize in American-Italian Relations) in Technical and Technological Science for "overcoming the boundaries of science and the development of technology, in order to improve the quality of human life and protection of the environment"
2014 - Mesothelioma Applied Research Foundation-Pioneer Award for "discovering the BAP1 cancer syndrome"
2008 - Landon Foundation-AACR INNOVATOR Award for International Collaboration in Cancer Research for "discovering the causes of the Mesothelioma epidemics in Cappadocia, Turkey"
2001 - Knight of the Republic of Italy (Cavaliere della Repubblica)
Research Focus
h-index: 83 (Publications on Google scholar)
Investigating an epidemic of mesothelioma in remote villages in Cappadocia, Turkey, Carbone first hypothesized and then proved that mesothelioma, cancer of the membranes, was caused by inherited genetic susceptibility to carcinogenic mineral fibers present in the environment (Roushdy-Hammady I,..& Carbone M, The Lancet, 2001; Dogan UA,..& Carbone M, Cancer Res, 2006; Carbone M, et al., Proc Natl Acad Sci USA, 2011).
Subsequently, Carbone discovered that inherited mutations of the BRCA1-associated protein 1 (BAP1) gene caused mesothelioma and other environment-related cancers (Testa JR,..& Carbone M, Nat Genet, 2011), a condition he named “The BAP1 cancer syndrome” (Carbone M, et al., J Transl Med, 2012 and Nat Rev Cancer, 2013). Carbone elucidated the molecular mechanisms by which BAP1 modulates gene-environment interaction in human, causing carcinogenesis (Bononi A,.. & Carbone M, Nature, 2017; Bononi A,..& Carbone M, Cell Death Differ, 2017), and elucidated mechanisms that regulate BAP1 and asbestos in gene-environment interaction and its clinical implications (Patorino S., et al., JCO, 2018; Carbone M., et al., Nat Rev Cancer, 2020; Carbone et al., Cancer Discovery, 2020; Xue J et al., PNAS, 2020; Novelli F. et al., PNAS, 2021).
Carbone discovered additional germline mutations that predispose to mesothelioma and gene-environment carcinogenesis (Bononi A. et al., PNAS, 2020). Most recently, Carbone and collaborators discovered that BAP1 stabilizes HIF-1 alpha in hypoxia, providing a mechanistic rationale for the less aggressive phenotype of BAP1-mutated mesotheliomas (Bononi A., et al., PNAS, 2023).
Clinical. Dr. Carbone is board-certified in Anatomic Pathology (both in Italy and the U.S.) and specializes in pleural pathology and mesothelioma.
Selected Publications
Suarez JS, Novelli F, Goto K, Ehara M, Steele M, Kim JH, Zolondick AA, Xue J, Xu R, Saito M, Pastorino S, Minaai M, Takanishi Y, Emi M, Pagano I, Wakeham A, Berger T, Pass HI, Gaudino G, Mak TW, Carbone M*, Yang H. HMGB1 released by mesothelial cells drives the development of asbestos-induced mesothelioma. (2023) Proc Natl Acad Sci U S A. 26;120(39):e2307999120. *co-corresponding author, doi: 10.1073/pnas.2307999120. Epub 2023 Sep 20. PMID: 37729199; PMCID: PMC10523480 Impact Factor: 11.1
Bononi A, Wang Q, Zolondick AA, Bai F, Steele-Tanji M, Suarez JS, Pastorino S, Sipes A, Signorato V, Ferro A, Novelli F, Kim J, Minaai M, Takinishi Y, Pellegrini L, Napolitano A, Xu R, Farrar C, Goparaju C, Bassi C, Negrini M, Pagano I, Sakamoto G, Gaudino G, Pass HI, Onuchic JN, Yang H, Carbone M. (2023). BAP1 is a novel regulator of HIF-1α. Proc Natl Acad Sci U S A. 120(4):e2217840120. doi:10.1073/pnas.2217840120. PubMed PMID: 36656861; PMC9942908. Impact Factor: 11.1
Carbone M, Pass HI, Ak G, Alexander HR Jr, Baas P, Baumann F, Blakely AM, Bueno R, Bzura A, Cardillo G, Churpek JE, Dianzani I, De Rienzo A, Emi M, Emri S, Felley-Bosco E, Fennell DA, Flores RM, Grosso F, Hayward NK, Hesdorffer M, Hoang CD, Johansson PA, Kindler HL, Kittaneh M, Krausz T, Mansfield A, Metintas M, Minaai M, Mutti L, Nielsen M, O'Byrne K, Opitz I, Pastorino S, Pentimalli F, de Perrot M, Pritchard A, Ripley RT, Robinson B, Rusch V, Taioli E, Takinishi Y, Tanji M, Tsao AS, Tuncer AM, Walpole S, Wolf A, Yang H, Yoshikawa Y, Zolondick A, Schrump DS, Hassan R. (2022). Medical and surgical care of patients with mesothelioma and their relatives carrying germline BAP1 mutations. J Thorac Oncol; 17:873-889, doi: 10.1016/j.jtho.2022.03.014. Impact Factor: 20.4.
Novelli F, Bononi A, Wang Q, Bai F, Patergnani S, Kricek F, Haglund E, Suarez J, Tanji M, Xu R, Takinishi Y, Minaai M, Pastorino S, Morris P, Sakamoto G, Pass HI, Barbour H, Gaudino G, Giorgi C, Pinton P, Onuchic JN, Yang H, Carbone M. (2021). BAP1 forms a trimer with HMGB1 and HDAC1 that modulates Gene X Environment interaction with asbestos. Proc Natl Acad Sci USA; 118 (48):e2111946118, doi: 10.1073/pnas.2111946118. Impact Factor: 11.1
Bononi A, Goto K, Ak G, Yoshikawa Y, Emi M, Pastorino S, Carparelli L, Ferro A, Nasu M, Kim J-H, Suarez JS, Xu R, Tanji M, Takinishi Y, Minaai M, Novelli F, Pagano I, Gaudino G, Pass HI, Groden J, Grzymski JJ, Metintas M, Akarsu M, Morrow B, Hassan R, Yang H, Carbone M. (2020). Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma. Proc Natl Acad Sci USA; 117:33466-33473, doi: 10.1073/pnas.2019652117. PMID: 33318203; PMCID: PMC7776606. Impact Factor: 11.1 Xue J, Patergnani S, Giorgi C, Suarez J, Goto K, Bononi A, Tanji M, Novelli F, Pastorino S, Xu R, Caroccia N, Dogan AU, Pass HI, Tognon M, Pinton P, Gaudino G, Mak TW, Carbone M*, Yang H. (2020). Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy. Proc Natl Acad Sci USA; 117:25543-25552, *co-corresponding author, doi: 10.1073/pnas.2007622117. PMID: 32999071; PMCID: PMC7568322. Impact Factor: 11.1
Bononi A, Giorgi C, Patergnani S, Larson D, Verbruggen K, Tanji M, Pellegrini L, Signorato V, Olivetto F, Pastorino S, Nasu M, Napolitano A, Gaudino G, Morris P, Sakamoto G, Ferris LK, Danese A, Raimondi A, Tacchetti C, Kuchay S, Pass HI, Affar EB, Yang H, Pinton P, Carbone M. (2017). BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Nature; 546:549-553, doi: 10.1038/nature22798. Impact Factor: 64.8
Selected Reviews
Carbone M, Arron ST, Beutler B, Bononi A, Cavenee W, Cleaver JE, Croce CM, D’Andrea A, Foulkes WD, Gaudino G, Groden JL, Henske EP, Hickson ID, Hwang PM, Kolodner RD, Mak TW, Malkin D, Monnat RJ Jr, Novelli F, Pass HI, Petrini JH, Schmidt LS, Yang H. (2020). Tumour predisposition and cancer syndromes as models to study gene X environment interactions. Nat Rev Cancer; 20:533-549, (Perspective). doi:10.1038/s41568-020-0265-y. Impact Factor 78.5
Carbone M, Harbour JW, Brugarolas J, Bononi A, Pagano I, Dey A, Krausz T, Pass HI, Yang H, Gaudino G. (2020). Biological mechanisms and clinical significance of BAP1 mutations in human cancer. Cancer Discovery; 10:1103-1120, doi: 10.1158/2159-8290.CD-19-1220. Impact Factor 28.2
Carbone M, Adusumilli PS, Alexander HR, Baas P, Bardelli F, Bononi A, Bueno R, Felley-Bosco E, Galateau-Salle F, Jablons D, Mansfield AS, Minaai M, de Perrot M, Pesavento P; Rusch V, Severson DT, Taioli E, Tsao A, Woodard G, Yang H, Zauderer MG, Pass HI. (2019). Mesothelioma: Scientific Clues for Prevention, Diagnosis, and Therapy. Ca Cancer J Clin; 69:402-429, doi.org/10.3322/caac.21572. Impact Factor: 254.7
Publication list via PubMed
Active Grants
M. Carbone, Contact PI; H. Yang, Co-PI
NCI
1R01CA237235
"Mechanisms of BAP1 activity in human cancer development"
12/13/19–11/30/24
M. Carbone, Contact PI, H. Yang (U. Hawaiʻi), Grzymski, DRI, Nevada, Co-PIs
NIEHS
1R01ES030948
"Influence of germline mutations on susceptibility to environmental carcinogens"
08/15/19–06/30/24 (NCE)
M. Carbone, PI
UH Foundation through unrestricted donations from Honeywell Int. Inc., Riviera United-4-a Cure, Maurice and Joanna Sullivan Family Foundation
"Pathogenesis of Malignant Mesothelioma”
07/01/10–ongoing
