Haining Yang, MD, PhD

Haining Yang, MD, PhD

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Full Member, Cancer Biology Program, University of Hawaiʻi Cancer Center

Academic Appointment(s):
Researcher (Professor), University of Hawaiʻi Cancer Center, University of Hawaiʻi at Mānoa

Degree(s):
MD, Shandong Medical University, P.R. China
PhD, Shandong University, P.R. China

Honors

2005, EU Marie Curie Scholarship by the European Commission Marie Curie Actions Program
2008, Landon AACR Innovator Award for International Collaboration in Cancer Research

Research Focus

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.

Selected Publications

Bononi A*, Yang H*, Giorgi C*, Patergnani S, Pellegrini L, Su M, Xie G, Signorato V, Pastorino S, Morris P, Sakamoto G, Kuchay S, Gaudino G, Pass HI, Napolitano A, Pinton P, Jia W, Carbone M. (2017). Germline BAP1mutations induce a Warburg effect. Cell Death Differ, June 30. doi: 10.1038/cdd,2017.95. Epub ahead of print.(* These authors contributed equally to this work).

Bononi A, Giorgi C, Patergnani S, Larson D, Verbruggen K, Tanji M, Pellegrini L, Signorato V, Olivetto F, Pastorino S, Nasu M, MNapolitano A, Gaudino G, Morris ,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. (* co-corresponding authors).

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.

Publication list via PubMed

Active Grants

H. Yang, Co-PI, (H. I. Pass, PI)
NCI
1 U01CA214195-01
"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.
09/01/16-08/31/21

H. Yang, Initiating PI; Partnering PIs: M. Carbone, H.I. Pass, T. Mak, S. Kanodia
CA150671P1
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 – 06/30/19

H. Yang, M. Carbone, Co-PIs
CA150220
DoD PRCRP - Idea Award
"Identification and Validation of Novel Germline DNA Variants Associated to Increased Risk of Malignant Mesothelioma"
10/01/16-09/30/18