Faculty

• Assistant Professor
  Cancer Biology Program
  University of Hawaii Cancer Center

Degrees

• 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. Yang’s research focuses on asbestos carcinogenesis and mesothelioma pathogenesis. Malignant mesothelioma is a very aggressive tumor and has been linked to occupational and environmental exposure to asbestos, causing about 3,000 deaths per year in the U.S. and over 100,000 deaths per year worldwide. With the lack of effective strategies to diagnose, prevent and treat mesothelioma, 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 was unexplained. Dr. Yang’s findings that TNF-alpha, induced by asbestos, led to the activation of an NF-kB 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). Recently, she made another important discovery about the mechanisms of asbestos carcinogenesis. She found the critical role of macrophages and of the inflammatory mediator, HMGB1, which is released by damaged mesothelial cells in response to asbestos exposure. HMGB1 initiates the inflammatory process that is related to mesothelioma development (Yang H. et al., Proc Natl Aca Sci USA, 2010). Dr. Yang also found that mesothelioma cells are “addicted” to HMGB1 even after the cells get transformed, and that HMGB1 contributes to tumor growth and survival. Therefore, inhibiting HMGB1 can be a novel therapeutic strategy for mesothelioma. Moreover, the research work of Dr. Yang also covers the studies on mesothelioma early detection by using some promising biomarkers, as well as the studies on new chemotherapeutic drugs.

Dr. Yang’s research goal is to identify the mechanisms responsible for asbestos carcinogenesis and to develop specific approaches for early detection and treatment. The results coming from her research projects may lead to some novel strategies for therapy or prevention that are likely to benefit millions people exposed to asbestos and to other carcinogenic mineral fibers in the US and worldwide.

Publications

• Yang H, Bocchetta M, et al. TNF-a inhibits asbestos induced cytotoxicity via a NF-kB dependent pathway, a possible mechanism for asbestos-induced oncogenesis. Proc Natl Acad Sci USA, 2006, 103(27): 10397-10402. PMCID: PMC1502469
• Yang H, Rivera Z, Jube S, Nasu M, Bertino P, Goparaju C, Franzoso G, Lotze MT, Krausz T, Pass HI, Bianci ME, Carbone M.  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, 2010, 107:12611-12616. PMID: 20616036; PMCID: PMC2906549
• Nasu M, Carbone M, Gaudino G, Ly BH, Bertino P, Shimizu D, Morris P, Pass HI, Yang H. Ranpirnase interferes with NF-κB pathway and MMP9 activity, inhibiting Malignant Mesothelioma cell invasiveness and xenografts growth. Gene & Cancer. 2011, 2: 563-575.
• Carbone M, Baris YI. Bertino P, Brass B, Comertpay S, Dogan AU. Gaudino G, Jube S, Kanodia S, Partridge CR, Pass HI, Rivera Z, Steele IM, Tuncer M, Way S, Yang H, Miller A. Erionite Exposure in North Dakota and in the Turkish Villages with Mesothelioma. Proc Natl Acad Sci USA, 2011, Epub ahead of print. PMID: 21788493
• 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. Germline Bap1 mutations predispose to malignant mesothelioma. Nat Genet. 2011, Epub ahead of print.
• Carbone M, Ly BH, Dodson RF, Pagano I, Morris PT, Dogan UA, Gazdar AF, Pass HI, Yang H. Malignant Mesothelioma: Facts, Myths and Hypotheses. Journal of Cellular Physiology, 2012, 227: 44-58. PMID: 21412769.
  
• Carbone M, Yang H. Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. (http://www.ncbi.nlm.nih.gov.eres.library.manoa.hawaii.edu/pubmed/22065079 ) Clin Cancer Res. 2012, 18: 598-604. PMID: 22065079
  
• Jube S, Rivera Z, Bianchi ME, Powers A, Wang E, Pagano IS, Pass HI, Gaudino G, Carbone M, Yang H. Cancer Cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res. 2012, 72: 3290-3301. PMID: 22552293 (This paper made the cover of the July 1st 2012 issue of Cancer Research)
  

Publication list via PubMed

Active Grants

Ongoing Research Support

• R01CA160715-01, Yang (PI)
  07/01/11-06/30/16
  The Role of HMGB1 in the Pathogenesis of Mesothelioma
  
• United-4 A Cure Foundation, Yang (PI)
  04/01/12-03/31/13
  Cancer Preventive Studies on Malignant Mesothelioma
  
• The V Foundation, Yang (co-PI)
  10/31/12-10/30/15
  HMGB1: A Biomarker for Mineral Fiber Exposure and Detection of Malignant Mesothelioma
  

Completed Research Support

• Mesothelioma Applied Research Foundation (Yang, PI)
  01/01/09-12/31/10
  Studies of TNFa as a new Target for Human Malignant Mesothelioma Preventive and Therapeutic Strategies.
• United-4 A Cure Foundation, Yang (PI)
  07/01/08-06/31/11
  Gene Expression Profiling Studies of Malignant Mesothelioma
• Hawaii Community Foundation, Yang (PI)
  09/24/08-09/24/11
  Mesothelioma Prevention and Early-detection Studies