Haining Yang, MD, PhD
- Associate Researcher (Associate 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
Since 2003, Dr. Yang has been studying how asbestos causes malignant mesothelioma (MM) with the ultimate goal of identifying novel strategies for prevention, early detection and therapy. In the U.S., it is estimated that more than 20 million people have been exposed to asbestos and are at risk of developing MM during the next decades. About 3,200 cases of MM are diagnosed each year. While the incidence has stabilized in the U.S. since 1995, it continues to rise in Europe and in third world countries. With the lack of effective strategies to diagnose, prevent and treat MM, median survival is only about 12 months from diagnosis. The mechanisms of asbestos-induced carcinogenesis are still unclear and the paradox of how asbestos, a mineral fiber that causes cell death, could lead to malignant transformation is unexplained. Dr. Yang's findings that chronic inflammation and TNF-ï¡ release, induced by asbestos, led to the activation of an NF-ï«B mediated survival mechanism that protects asbestos-damaged mesothelial cells from dying, thereby enabling them to divide and eventually become transformed, provide a rationale to this paradox (Yang H, et al, Proc Natl Aca Sci USA, 2006).
In the course of this work Dr. Yang became part of a team of investigators, led by Dr. Carbone, that studies asbestos and mesothelioma, and in 2008 she and her group received the Landon AACR Innovator Award for International Collaboration in Cancer Research. In March 2009 she became a tenure-track Assistant Professor in the University of Hawaii, then she was promoted to Associate Professor at the University of Hawaii Cancer Center in May 2013 and obtained tenure in June 2014.
Her studies on asbestos carcinogenesis were and are supported by grants from the MARF Foundation, from the Hawaii Community Foundation, and one R01 that was funded by the NCI in 2011. These studies led to findings describing the role of macrophages and of the inflammatory mediator, HMGB1, which is released by damaged mesothelial cells and macrophages in response to asbestos exposure (Yang H, et al, Proc Natl Aca Sci USA, 2010). These findings suggest that HMGB1 may be the "master switch' that initiates the inflammatory reaction, which favors asbestos-pathogenesis and carcinogenesis and the growth of mesothelioma. Moreover, she and her team found that mesothelioma cells are "addicted" to HMGB1 (Jube S, et al, Cancer Res 2012) and that targeting HMGB1 inhibits tumor growth and progression. More recently Dr. Yang's group has found that the hyper-acetylated form of HMGB1 isoform is a sensitive and specific serum biomarker to detect asbestos exposure and to identify mesothelioma patients (Napolitano, et al, Clin Cancer Res, 2016). These results are of high clinical relevance as they provide the first biomarker of asbestos exposure and indicate that hyper-acetylated HMGB1 is an accurate biomarker to differentiate MM patients from individuals occupationally exposed to asbestos and unexposed controls. A trial to independently validate these findings is in preparation.
Other research goals are to study, in addition to asbestos, the mechanism(s) of carcinogenesis of other carcinogenic particles-mediated carcinogenesis and to study, at large, the mechanisms of pathogenesis of mesothelioma, including investigating whether BAP1 mutations, germline genetic mutations that cause a new cancer syndrome including mesothelioma, influence HMGB1 levels that lead to predisposition to mesothelioma development. All these studies will hopefully lead to novel strategies for mesothelioma early detection, prevention and therapy.
- 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, Initiating PI; Partnering PIs: M. Carbone, H.I. Pass, T. Mak, S. Kanodia
DoD (Peer Reviewed Cancer Research Program âTranslational 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)
- H. Yang, M. Carbone, Co-PIs
"Identification and Validation of Novel Germline DNA Variants Associated to Increased Risk of Malignant Mesothelioma"
$616,000 (Total direct cost)
- 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.
H. Yang, PI
DoD Career Development Award
"Mesothelioma: identification of the key molecular events triggered by BAP1"
The overall goal of this project was to explore the possible interactions between the pathways activated by HMGB1 and those that are altered by BAP1 deletions. It is anticipated that these studies will lead to the identification of the cellular pathways that are critical in the process of asbestos carcinogenesis and mesothelioma growth, and thus provide specific targets to develop novel molecular therapeutic approaches.