Giovanni Gaudino, PhD
Cancer Biology Program
University of Hawaii Cancer Center
- PhD, Biochemistry
University of Torino, Italy
- MS, Biological Sciences
University of Torino, Italy
The main focus of my research is to understand the mechanisms of molecular carcinogenesis of asbestos-induced initiation, maintenance and progression of Malignant Mesothelioma (MM). The goal is to enable the development of novel strategies for the prevention and/or therapy of MM. I have a broad experience in oncogene-mediated signal transduction. In particular, my main achievements on MM are: 1) I identified HGF/Met and VEGF/Flk-1 autocrine loops for receptor tyrosine kinases responsible for mesothelial cell transformation; 2) I demonstrated that constitutive Akt activity drives mesothelial cell transformation after exposure to asbestos or asbestos-like (erionite) fibers and, together with NF-├┐B pathways, sustains MM survival and chemoresistance; 3) I discovered the molecular mechanism of taurolidine induced apoptosis of MM cells, via oxidative stress and Akt inactivation; 4) I showed the first microarray cross-evaluation of microRNA and mRNA expression in MM, with diagnostic and prognostic implications; 5) I identified the mechanisms of different SV40 strains for tropism toward astrocytes and mesothelial cells; and 6) I demonstrated the molecular mechanisms of onconase anti-tumor activity in MM.
These preclinical studies led to the following therapeutic approaches: a) the combined treatment of the tyrosine kinase inhibitor Imatinib mesylate (Gleevec┬«) with gemcitabine, inducing MM remission in SCID xenografts (currently in phase II clinical trials); b) the treatment with the proteasome inhibitor bortezomib(PS-341, Velcade┬«), blocking MM growth (currently in phase II clinical trials).
More recently I contributed to the discovery of a new syndrome, caused by germline BAP1 gene mutations, characterized by the development of MM, uveal melanoma, atypical melanocytic tumors and other cancers.
I have established a record of successful productive research and applications in the area of MM targeted therapy.
- Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. (2013). Bap1 and Cancer. Nat Rev Cancer, 13: 153-159. PMID: 23550303. Qi F, Okimoto G, Jube S, Napolitano A, Pass HI, Laczko R, Demay R, Khan G, Tiirikainen M, Rinaudo C, Croce A, Yang H, Gaudino G, Carbone M. (2013). Continuous Exposure to Chrysotile Asbestos Can Cause Transformation of Human Mesothelial Cells via HMGB1 and TNF-├┐ Signaling. Am J Pathol, 183: 1654-1666. PMID: 24160326.
- Busacca S, Chacko AD, Klabatsa A, Arthur K, Sheaff M, Gunasekharan VK, Gorski JJ, El-Tanani M, Broaddus VC, Gaudino G, Fennell DA. (2013). - BAK and NOXA Are Critical Determinants of Mitochondrial Apoptosis Induced by Bortezomib in Mesothelioma. PLoS One, Jun 7; 8(6):e65489. PMID: 23762382.
- Rivera Z, Ferrone S, Wang X, Jube S, Yang H, Pass HI, Kanodia S, Gaudino G, Carbone M (2012)CSPG4 as a target of antibody-based immunotherapy for malignant mesothelioma. Clin Cancer Res, 18:5352-63. PMID: 22893632.
- 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. Nature Genetics, 43: 1022-1025. PMID 21874000.
Publication list via PubMed