Program Director/Principal Investigator (Last, First, Middle):
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Yong Lin
Scientist
eRA COMMONS USER NAME (credential, e.g., agency login)
YLIN00
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
West China University of Medical Sciences
(WCUMS) Chengdu, China
West China University of Medical Sciences
(WCUMS), Chengdu, China
Kanazawa University, Kanazawa, Ishikawa, Japan
DEGREE
(if applicable)
YEAR(s)
M.D.
1984
Medicine
M.S.
1987
Medical Sciences
Ph.D.
1998
Molecular Biology
FIELD OF STUDY
A. Personal Statement
The goal of this application is to determine the role and underlying mechanism of necroptosis in
chemoprevention against lung cancer. I have the essential expertise and motivation necessary to carry out
the proposed research. Residing in Lovelace Biomedical and Environmental Research Institute (LBERI) that
has a specific commitment and environment for lung disease research, my laboratory investigates the roles
and mechanisms of cell survival and death signaling pathways involved in lung carcinogenesis and
anticancer therapy. The recently identified necroptosis pathway, for defining which my research has
substantial contributions, is one of the major pathways for cell death. This application focusing on necroptosis
for lung carcinogenesis is highly innovative. With our extensive and experience in molecular biology and cell
death and survival signaling research in lung cancer, we are at a unique position in conducting the proposed
research and I am qualified to lead the proposed research project. Successful completion of this project will
establish a novel mechanism lung cancer development, which will open an important avenue for improving
chemoprevention efficacy against lung cancer.
B. Positions and Honors.
Positions and Employment
1993 - 1995
Special Foreign Researcher, Department of Molecular Oncology, Cancer Research Institute,
Kanazawa University, Kanazawa, Japan
1998
Lecturer, Department of Molecular Oncology, Cancer Research Institute, Kanazawa, Japan
1998 - 2003
Postdoctoral Visiting Fellow, Cell and Cancer Biology Branch, NCI, NIH, Bethesda, MD
2003 - 2004
Research Fellow, National Cancer Institute, NIH, Bethesda, MD
2004 - 2010
Associate Scientist (equivalent to assistant professor, tenure-track), Molecular Biology and
Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM
2010 - present Scientist (equivalent to associate professor), Molecular Biology and Lung Cancer Program,
Lovelace Respiratory Research Institute, Albuquerque, NM
Honors
Research Excellence Award for Foreign Students by Sasakawa Memorial Foundation, Japan, 1997
Fellowship Advancement Award, DCS, NCI, NIH, 2000
Fellow Award for Research Excellence 2000 (FARE2000), NIH, 2000
Fellowship Advancement Award, DCS, NCI, NIH, 2001
Fellow Award for Research Excellence 2003 (FARE2003), NIH, 2003
Travel Award to attend Experimental Biology 2003 Annual Meeting. American Society for Biochemistry and
Molecular Biology, 2003
Travel Award to attend IUBMB/ASBMB Annual Meeting. American Society for Biochemistry and Molecular
Biology, 2004
Reviewer, American Association for Cancer Research Centennial Grants Committee (2008)
Reviewer, Wellcome Trust Research Career Development Fellowship (2007, 2009, 2010)
Reviewer, Research Grants Council, Hong Kong (2010, 2012)
PHS 398/2590 (Rev. 11/07)
Page
1
Biographical Sketch Format Page
Program Director/Principal Investigator (Last, First, Middle):
Reviewer, Breast Cancer Research Program, US Department of Defense (DoD) Congressionally Directed
Medical Research Programs (CDMRP) (2010)
Reviewer, National Natural Science Foundation of China (2011, 2012)
Reviewer, NCI Cancer Prevention Research Small Grant Program, SRLB-Y(O2) (2011)
Reviewer, Foundation for Polish Science (Poland); Team Program grant. (2011)
Reviewer, Lung Cancer Research Program (LCRP), US DoD Congressionally Directed Medical Research
Programs (CDMRP) (2011)
Reviewer, Cancer Provocative Questions grant program special emphasis panel. ZCA1 SRLB-D (M1) R
2012/05 ZCA1 SRLB-9 (M1) R , NIH/NCI (2012)
Reviewer, Oncology Basic Translational (OBT) IRG. Special Emphasis Panel/Scientific Review Group
2012/10 ZRG1 OBT-M (02) M. NIH (2012).
C. Selected peer-reviewed publications (in chronological order, selected from 69 papers).
Most relevant to this project:
1.
Lin Y, A. Devin, Y. Rodriguez, Z-G Liu. Cleavage of the death domain kinase RIP by Caspase-8
prompts TNF-induced apoptosis. Genes Dev. 1999, 13: 2514-2526.
2.
Lin, Y., S. Choski, H. M. Shen, Q. F. Yang, G. M. Hur, Y. S. Kim, J. H. Tran, S. A. Nedospasov,
Z-G. Liu. Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting proteinmediated cellular reactive oxygen species accumulation. J. Biol. Chem. 279: 10822-10828, 2004.
3.
Wang, X., W. Ju, J. Renouard, J. Aden, S. A. Belinsky Lin Y. 17-Allylamino-17-demethoxygeldanamycin
synergistically potentiates tumor necrosis factor-induced lung cancer cell death by blocking the nuclear
factor-B pathway. Cancer Res. 66(2): 1089-1095, 2006.
4.
Xu X., Bai L., Chen W., Padilla M.T., Liu Y., Kim K. C., Belinsky S. A., Lin Y. MUC1 contributes to BPDEinduced human bronchial epithelial cell transformation through facilitating EGFR activation. PloS One.
2012;7:e33846.
5.
He W., Wang Q., Srinivasan B., Xu J., Padilla MT, Li Z., Wang X., Gou X., Shen HM, Xing C., Lin Y.
JNK-mediated autophagy pathway that triggers c-IAP degradation and necroptosis for anticancer
chemotherapy. Oncogene. Under revision.
Additional recent publications important to the field:
6.
7.
8.
9.
10.
11.
12.
13.
Devin, A., A. Cook, Lin Y., Y. Rodriguez, M. Kelliher, Z.-G. Liu: The distinct roles of TRAF2 and RIP in
TNF-R1-mediated IKK activation: IKK is recruited to the TNF-R1 complex via TRAF2 while its activation
is mediated by RIP. Immunity 12: 419-429, 2000.
Lin, Y., A. Devin, A. Cook, M. M. Keane, M. Kelliher, S. Lipkowitz, Z.-G. Liu. The death domain kinase
RIP is essential for TRAIL/Apo2L-induced activation of IκB kinase (IKK) and C-Jun N-terminal kinase
(JNK). Mol. Cell Biol. 20: 6638-6645, 2000.
Yang, J.*, Lin Y. *, Z. Guo, H. Huang., W. Liao, Z.-G. Liu, B. Su. The MAP kinase kinase3 (MEKK3) is
essential for TNF-induced NF-κB activation. Nat. Immunol. 2: 620-624, 2001. *Equal contribution
Huang, Q., J. Yang, Y. Lin, C. Walker, J. Cheng, Z.-G. Liu, Su B. Differential regulation of interleukin 1
receptor and toll-like receptor signaling by MEKK3. Nat. Immunol. 5: 98-103, 2004.
Shen HM, Lin Y, Jin J, Chang L, Karin M, Zhang J, Liu Zg. The Essential Role of RIP and TRAF2 in
Oxidative Stress-Induced Cell Death. Mol Cell Biol, 2004. 24: 24: 5914-5922.
Yang Q, Huang W., Jozwik C., Lin Y., Glasman M Caohuy H, Srivastava M, Pollard HB. Cardiac
glycosides inhibit TNFa/NFkB signaling by blocking recruitment of TRADD to the TNF receptor. Proc
Natl Acad Sci U S A. 2005.
Choksi S. #, Lin Y. #, Y. Pobezinskaya#, L Chen#, X. Cao, T. Li, C. Park, Y. Kim, H-S. Kim, M. Morgan, P.
Levitt, M. Birrer, C-X Deng, Z-G Liu. A novel HIF-1 target, ATIA, protects cells from apoptosis by
modulating the mitochondrial thioredoxin, TRX2. Molecular Cell. 42: 597-609, 2011. #Equal
contributions.
Xu X., Bai L., Chen W., Padilla M.T., Liu Y., Kim K. C., Belinsky S. A., Lin Y. MUC1 contributes to BPDEinduced human bronchial epithelial cell transformation through facilitating EGFR activation. PloS One.
2012;7:e33846.
PHS 398/2590 (Rev. 11/07)
Page
2
Continuation Format Page
Program Director/Principal Investigator (Last, First, Middle):
14. Chen W, Xu X, Bai L, Padilla MT, Gott KM, Leng S, Tellez CS, Wilder JA, Belinsky SA, Scott BR, Lin Y.
Low-dose gamma-irradiation inhibits IL-6 secretion from human lung fibroblasts that promotes bronchial
epithelial cell transformation by cigarette smoke carcinogen. Carcinogenesis. 2012;33:1368-1374
15. He W., Wang Q., Xu J., Xu X., Padilla MT., Ren G., Gou, X., Lin Y. Attenuation of TNFSF10/TRAILinduced apoptosis by an autophagic survival pathway involving TRAF2- and RIPK1/RIP1-mediated
MAPK8/JNK activation. Autophagy, 2012, 8(12):1811-1821.
16. Leng S, Picchi MA, Liu Y, Thomas CL., Willis DG., Bernauer AM., Carr TG., Mabel PT, Han Y., Amos CI,
Lin Y., Stidley CA., Gilliland FD., Jacobson MR., Belinsky SA. Genetic variation in SIRT1 affects
susceptibility of lung squamous cell carcinomas in former uranium miners from the Colorado plateau.
Carcinogenesis. 2013. Accepted.
D. Research Support.
Active
R01ES017328
(PI: Lin)
08/09/2010 - 03/31/2015
5.0 Person-months
Bridging Inflammation & Cigarette Smoke-associated Lung Carcinogenesis by MUC1
NIEHS/NIH
Role: Principal Investigator
The proposed research is to study the molecular mechanism underlying tobacco smoke-induced lung
inflammation-associated carcinogenesis.
DE-SC0001173 (PI: Scott)
07/15/2009 - 03/14/2013
3.0 Person-months
Biological Bases for Radiation Adaptive Responses in the Lung
Department of Energy
Role: Subproject PI
The overall objective of this proposal is to elucidate the biological bases for low-dose, low-LET-radiationinduced adaptive responses in the lung and use the knowledge gained to produce an improved systemsbiology-based, risk model for lung cancer.
Completed
R03CA125796 (PI: Lin)
6/15/07 – 5/31/09
Nutrient Flavonoids and Lung Cancer Prevention
NCI/NIH
Role: Principal Investigator
The goal of this project was to determine the mechanism by which the nature flavonoid luteolin induces
apoptosis in lung cancer cells.
PHS 398/2590 (Rev. 11/07)
Page
3
Continuation Format Page