Haining Yang, MD, PhD
- Researcher (Professor)
and Full Member
Cancer Biology Program
University of Hawaii Cancer Center
- MD, Shandong Medical University, P.R. China
- PhD, Shandong University, P.R. China
- 2005, EU Marie Curie Scholarship by the European Commission Marie Curie Actions Program
- 2008, Landon AACR Innovator Award for International Collaboration in Cancer Research
Dr. Haining Yang's research work focuses on the pathogenesis of mesothelioma, a malignancy often related to exposure to asbestos or other carcinogenic mineral fibers. Her research goal is to find novel strategies for mesothelioma early detection, prevention and therapy. During years of study, Dr. Yang has discovered some key mechanisms of asbestos-induced carcinogenesis. She found that asbestos induces cell necrosis, causing the release of a critical factor called High Mobility Group Box 1 protein (HMGB1). HMGB1 functions as the "master switch" that when turned on, kick starts a series of inflammatory responses that over time lead to malignant transformation of mesothelial cells and mesothelioma development (Yang H. et al., Proc Natl Aca Sci USA 2006, and Yang H. et al., Proc Natl Aca Sci USA 2010). Moreover, she found that mesothelioma cells that grow out of an HMGB1-rich environment are "addicted" to HMGB1 and require it for tumor growth and progression (Jube S. et al., Cancer Res, 2012). Therefore, Dr. Yang is exploring targeting HMGB1 as a novel therapeutic strategy for mesothelioma. Dr. Yang and her research team found that both mesothelioma patients and asbestos-exposed individuals have significantly higher serum HMGB1 levels compared to heavy smokers or healthy people. They also discovered that HMGB1 and its specific isoforms are sensitive and specific biomarkers to detect asbestos exposure and to identify mesothelioma patients (Napolitano, et al, Clin Cancer Res, 2016).
Besides the studies on HMGB1, Dr. Yang in collaboration with Dr. Michele Carbone, discovered that heterozygous germline BAP1 mutations predispose to malignant mesothelioma (Testa J et al, Nature Genetics, 2011). These findings opened a new research field studying the mechanisms of gene-environment interaction in causing mesothelioma, and led to the discovery of a new cancer syndrome that was named the "BAP1 cancer syndrome".
Dr. Yang's research is funded by the National Cancer Institute, the V-Foundation and the Department of Defense. Dr. Yang received EU Marie Curie Scholarship from the European Commission Marie Curie Actions Program in 2005, and she was one of the recipients of the American Association for Cancer Research (AACR) Innovative Landon Award for International Collaboration in Cancer Research in 2008. She has two approved and one pending patents on HMGB1 and mesothelioma.
- Napolitano A, Antoine DJ, Pellegrini L, Baumann F, Pagano I, Pastorino S, Goparaju CM, Prokrym K, Canino C, Pass HI, Carbone M, Yang H. (2016). HMGB1 and its hyper-acetylated isoform are sensitive and specific serum biomarkers to detect asbestos exposure and to identify mesothelioma patients. Clin Cancer Res; Published OnlineFirst January 5, 2016; doi:10.1158/1078-0432.CCR-15-1130.
- Carbone M, Flores EG, Emi M, Johnson TA, Tsunoda T, Behner D, Hoffman H, Hesdorffer M, Nasu M, Napolitano A, Powers 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 Gene, Dec 18;11(12):e1005633. PMID: 26683624.
- 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, Jun 11;6:e1786. PMID: 26068794.
- Carbone M, Yang H, Pass HI, Testa JR, Gaudino G. (2013). The BAP1 Cancer Syndrome. Nat Rev Cancer,13: 153-159. PMID: 23550303.
- Carbone M, Yang H. (2012). Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. Clin Cancer Res, 18: 598-604. PMID: 22065079 PMCID: PMC3291331.
- Jube S, Rivera Z, Bianchi ME, Powers A, Wang E, Pagano IS, Pass HI, Gaudino G, Carbone M, Yang H. (2012). Cancer Cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res, 72: 3290-3301. PMID: 22552293 (This paper made the cover of the July 1st 2012 issue of Cancer Research).
- 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 Genet, 43:1022-1025. PMID: 21874000.
- Yang H, Rivera Z, Jube S, Nasu M, Bertino P, Goparaju C, Franzoso G, Lotze MT, Krausz T, Pass HI, Bianci ME, Carbone M. (2010). 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. PMID: 20616036; PMCID: PMC2906549.
Publication list via PubMed
- H. Yang, Co-PI, (H. I. Pass, PI)
"The EDRN Mesothelioma Biomarker Discovery Laboratory"
The goal of this study is to develop novel tools to accurately and non-invasively (1) demonstrate asbestos exposure so that a subject could be monitored for asbestos-associated malignancy, (2) diagnose mesothelioma as early as possible in high risk populations, (3) distinguish early stage mesothelioma from other malignancies, and (4) define mesothelioma prognostic features at the time of diagnosis.
- H. Yang, Initiating PI; Partnering PIs: M. Carbone, H.I. Pass, T. Mak, S. Kanodia
DoD Peer Reviewed Cancer Research Program (PRCRP) - Translational Team Science Award
"HMGB1 and Its Isoforms as Biomarkers for Mineral Fiber Exposure and MM Detection"
07/01/16 â€“ 06/30/19
H. Yang, M. Carbone, Co-PIs
DoD PRCRP - Idea Award
"Identification and Validation of Novel Germline DNA Variants Associated to Increased Risk of Malignant Mesothelioma"
H. Yang, PI
"The Role of HMGB1 in the Pathogenesis of Mesothelioma "
The overall goal of this project is to elucidate the mechanism(s) by which HMGB1 contributes to asbestos-induced initiation, maintenance and progression of MM and evaluate inhibition of HMGB1 as a novel strategy for the prevention and/or therapy of MM.
H. Yang, Basic Science PI; M. Carbone, Clinical PI; I. Pagano, Biostatistician PI
The V Foundation, Translational Award
"HMGB1: A Biomarker for Mineral Fiber Exposure and Detection of Malignant Mesothelioma"
To examine HMGB1 as a biomarker of asbestos and erionite exposure and the early detection of mesothelioma, and to examine whether treatment with aspirin can affect HMGB1 levels in the serum.