BIOGRAPHICAL SKETCH
NAME
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.
Steven A. Belinsky
POSITION TITLE
Senior Scientist eRA COMMONS USER NAME (credential, e.g., agency login)
SBELINSKY
EDUCATION/TRAINING ( Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.
)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s) FIELD OF STUDY
The University of North Carolina, Chapel Hill, NC
The University of North Carolina, Chapel Hill, NC
A. Personal Statement
B.S.
Ph.D.
1978
1984
Biology
Toxicology
I have worked in the field of tobacco carcinogenesis for > 25 years conducting basic and translational research on lung cancer. My group first demonstrated that the tobacco specific nitrosamine NNK causes
DNA adducts that accumulate in the lung and lead to mutation of the K-ras oncogene. My research in epigenetics began in the 1990s with initial key studies identifying silencing of the p16 gene as an early event in lung cancer, the detection of promoter methylation of specific genes in sputum up to three years prior to clinical diagnosis, and the continued identification and evaluation of biomarkers for predicting lung cancer through assessment in sputum and blood. This work has been extended to identify epigenetically regulated microRNAs and we are currently assessing their potential as biomarkers for risk assessment. Thus, I have considerable experience in discovery, assessment, and testing of candidate biomarkers moving from animal models to humans.
B. Positions and Honors
Positions and Employment
1978 - 1979
1980 - 1984
1984 - 1986
Research Technician, Department of Pharmacology, The University of North Carolina,
Chapel Hill, NC
Graduate Student, Curriculum in Toxicology, The University of North Carolina, Chapel Hill, NC
Postdoctoral Fellow, National Institute of Environmental Health Sciences, Research Triangle
1986 - 1990
Park, NC
Senior Staff Fellow, National Institute of Environmental Health Sciences, Research Triangle
1990 - 1996
Park, NC
Staff Scientist, Inhalation Toxicology Research Institute, Albuquerque, NM
1991 - Present Clinical Associate Professor, College of Pharmacology, University of New Mexico,
Albuquerque, NM
1991 - Present Associate Scientist, University of New Mexico Cancer Center, University of New Mexico,
Albuquerque, NM
1992 - Present Adjunct Associate Professor, Department of Veterinary Pathology, Purdue University, West
Lafayette, IN
1997 - Present Program Manager, Molecular Biology and Lung Cancer Program; Senior Scientist, Lovelace
2001 - 2007
Respiratory Research Institute, Albuquerque, NM
Deputy Director, New Mexico NIEHS Center
2002 - Present Co-Director, Population Sciences Program, New Mexico Cancer Center
2010 - Present Vice President for Academic Research, Lovelace Respiratory Research Institute
Honors
1982 - 1984
1984 - 1986
2007
2009
Predoctoral Fellow, Environmental Toxicology, National Institute of Environmental Health
Sciences
Postdoctoral Fellow, National Research Service Award, National Institute of Environmental
Health Sciences
Loyd E. Harris Lecturer, University of Oklahoma, College of Pharmacy
The Alton Ochsner Award Relating Smoking and Health

C. Selected Peer-reviewed Publications
1. Belinsky, S. A., K. J. Nikula, S. B. Baylin and J.-P. Issa: Increased cytosine DNA-methyltransferase activity is target cell specific and an early event in lung cancer. Proc. Natl. Acad. Sci. USA 93 :
4045-4050, 1996.
2. Swafford, D. S., S. K. Middleton, W. A. Palmisano, K. J. Nikula, J. Tesfaigzi, J. G. Herman, S. B. Baylin and S. A. Belinsky: Frequent aberrant methylation of p16 INK4a in primary rat lung tumors. Mol. Cell Biol.
17 : 1366-1374, 1997.
3. Belinsky, S. A., K. J. Nikula, W. A. Palmisano, R. Michels, G. Saccomanno, E. Gabrielson, S. B. Baylin and J. G. Herman: Aberrant methylation of p16 INK4a is an early event in lung cancer and a potential biomarker for early diagnosis. Proc. Natl. Acad. Sci. USA 95 : 11891-11896, 1998. PMCID: PMC21736
4. Palmisano, W. A., K. K. Divine, G. Saccomanno, F. D. Gilliland, S. Goodman, S. B. Baylin, J. G.
Herman and S. A. Belinsky: Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res. 60 : 5954-5958, 2000.
5. Belinsky, S. A., D. M. Klinge, C. A. Stidley, J.-P. Issa, J. G. Herman, T. H. March and S. B. Baylin:
Inhibition of DNA methylation and histone deacetylation prevents murine lung cancer. Cancer Res. 63 :
7089-7093, 2003.
6. Belinsky, S. A.: Gene promoter hypermethylation as a biomarker in lung cancer. Nat. Rev. Cancer 4 :
707-717, 2004.
7. Belinsky, S. A.: Silencing of genes by promoter hypermethylation: Key event in rodent and human lung cancer. Carcinogenesis 26 : 1481-1487, 2005.
8. Belinsky, S.A., Klinge, D.M., Dekker, J.D., Smith, M.W., Bocklage, T.J., Gilliland, F.D., Crowell, R.E.,
Karp, D.D., Stidley, C.A., and Picchi, M.A. Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin. Cancer Res. 11: 6505 - 6511, 2005.
9. Belinsky, S. A., K. C. Liechty, F. D. Gentry, H. J. Wolf, J. Rogers, K. Vu, J. Haney, T. C. Kennedy, F. R.
Hirsch, Y. Miller, W. A. Franklin, J. G. Herman, S. B. Baylin and T. Byers: Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res. 66 : 3338-
3344, 2006.
10. Belinsky, S.A., Grimes, M.J., Casas, E., Stidley, C.A., Franklin, W.A., Bocklage, T.J., Johnson, D.A., and Schiller, J.H. Predicting gene promoter methylation in lung tumors by evaluating sputum and serum.
British J. Cancer. 96: 1278-1283, 2007.
11. Brock, M. V., C. M. Hooker, E. Ota-Machida, Y. Han, M. Guo, S. Ames, S. Gl öckner, S. Piantadosi, E.
Gabrielson, G. Pridham, K. Pelosky, S. A. Belinsky, S. C. Yang, S. B. Baylin and J. G. Herman: DNA methylation markers and early recurrence in stage I lung cancer. N. Engl. J. Med. 358 : 1118-1128,
2008.
12. Leng, S., C. A. Stidley, R. Willink, A. Bernauer, K. Do, M. A. Picchi, X. Sheng, M. A. Frasco, D.
Van Den Berg, F. D. Gilliland, C. Zima, R. E. Crowell and S. A. Belinsky: Double-strand break damage and associated DNA repair genes predispose smokers to gene methylation. Cancer Res. 68 : 3049-
3056, 2008. PMCID: PMC2483467
13. Tessema, M., R. Willink, K. Do, Y. Y. Yu, W. Yu, E. O. Machida, M. Brock, L. Van Neste, C. A. Stidley,
S. B. Baylin and S. A. Belinsky: Promoter methylation of genes in and around the candidate lung cancer susceptibility locus 6q23-25 . Cancer Res.
68 : 1707-1714, 2008.
14. Pulling, L. C., M. J. Grimes, L. A. Damiani, D. E. Juri, K. Do, C. S. Tellez and S. A. Belinsky: Dual promoter regulation of death-associated protein kinase gene leads to differentially silenced transcripts by methylation in cancer. Carcinogenesis 30 : 2023-2030, 2009.
15. Tessema, M., Y. Y. Yu, C. A. Stidley, E. O. Machida, K. E. Schuebel, S. B. Baylin and S. A. Belinsky:
Concomitant promoter methylation of multiple genes in lung adenocarcinomas from current, former and never smokers. Carcinogenesis 30 : 1132-1138, 2009.
16. Stidley, C. A., M. A. Picchi, S. Leng, R. Willink, R. E. Crowell, K. G. Flores, H. Kang, T. Byers, F. D.
Gilliland and S. A. Belinsky: Multivitamins, folate, and green vegetables protect against gene promoter methylation in the aerodigestive tract of smokers. Cancer Res. 70(2) : 568-574, 2010.
17. Tessema, M., Klinge, D.M., Yingling, C.M., Do, K., Van Neste, L., and Belinsky, S.A. Re-expression of the CXCL14 chemokine, a common target for epigenetic silencing in lung cancer induces tumor necrosis. Oncogene 29 :5159-5170, 2010.
18. Belinsky, S.A., Grimes, M.J., Picchi, M.A., Mitchell, H.D., Stidley, C.A., Tellez, C.S., Tesfaigzi, Y.,
Carter, M.M., Casero, R.A., Baylin, S.B., Reed, M.D., and March, T.H.
Combination therapy with vidaza

and entinostat suppresses tumor growth and reprograms the epigenome in an orthotopic lung cancer model. Cancer Res. 71:454-462, 2011.
19. Tellez, C. S., Juri, D.E., Do, K., Bernauer, A., Thomas, C., Damiani, L.A., Tessema, M., Leng, S., and
Belinsky, S.A. Carcinogen exposure induces EMT through epigenetic silencing of miR-205 and miR-200 family and promotes s Leng, S., C. A. Stidley, R. P. Willink, Y. Liu, M. A. Picchi, C. K. Edlund, D. Van
Den Berg, Y. Tesfaigzi, R. E. Crowell, F. D. Gilliland and S.A. Belinsky: Sequence variation in DNA replication and apoptosis genes affects promoter hypermethylation in sputum from lung cancer-free smokers. Cancer Res. 72 : 707-715, 2012.
20. Leng, S., K. Do, C. M. Yingling, M. A. Picchi, H. J. Wolf, T. C. Kennedy, W. J. Feser, A. E. Baron, W. A.
Franklin, M. V. Brock, J. G. Herman, S. B. Baylin, T. Byers, C. A. Stidley and S.A. Belinsky: Defining a gene promoter methylation signature in sputum for lung cancer risk assessment. Clin. Cancer Res.,
18 :3387-95, 2012.
D. Research Support.
Ongoing Research Support
2-P50-CA-58184 Baylin (PI)
NIH/SPORE (through Johns Hopkins)
6/1/01 – 11/30/13
Defining the Sensitivity of Methylation Biomarkers for Establishing Lung Cancer Risk and for Use in Intervention
Trials
This project will evaluate the ability of gene promoter hypermethylation as a biomarker to predict lung cancer risk.
Role: Co-Investigator of SPORE; Principal Investigator of this project
CA37403-18
NIH (subcontract through ECOG)
Comis (PI) 6/1/01 – 5/31/13
ECOG CCOP Research Base
To provide oversight for the selenium repository.
Role: Principal Investigator on subcontract
RO1-CA95568-06
NIH
Belinsky (PI) 2/1/03 – 1/31/14
Biomarkers to Assess Selenium Chemoprevention from NSCLC
To determine whether gene promoter hypermethylation detected in biological fluids can serve as a molecular marker system to predict the efficacy of selenium as a chemopreventive agent for NSCLC.
Role: Principal Investigator
RO1-CA97356-06 Belinsky (PI)
NIH
Factors for Epigenetic Silencing of Lung Cancer Genes
7/1/10 – 5/31/15
To conduct population-based studies of cancer-free male and female smokers to evaluate interrelationships between clinical risk factors, germ-line, and somatic changes for their contribution to lung cancer development.
Role: Principal Investigator
R01-ES015262-01 Belinsky (PI)
NIH
Genetic and Epigenetic Biomarkers for SCC of the Lung
7/1/08 – 6/30/13
To conduct laboratory studies to identify the effect of reduced expression of genes in DNA repair pathways on the induction of gene methylation and transformation of immortalized bronchial epithelial cells and the association of sequence variation in DNA repair genes to SCC in radon-exposed uranium miners.
Role: Principal Investigator
R01 HL107873-01 Belinsky/Tesfaigzi (PIs)
NIH
Epigenetic Changes Link COPD and Lung Cancer
9/8/11 – 9/7/15
To conduct laboratory and population-based studies to identify epigenetically silenced genes within the methylome that distinguish adenocarcinoma patients with and without COPD and to assess their utility as biomarkers for risk assessment in smokers with COPD.

Role: Co-Principal Investigator
DE-SC0001173 Scott (PI)
Department of Energy
Biological Bases for Radiation Adaptive Responses in the Lung
7/15/09 – 3/14/14
The overall object of this proposal is to elucidate the biological bases for low-dose, low-LET-radiation-induced adaptive responses in the lung and use the knowledge gained to produce an improved systems-based, risk model for lung cancer.
Role: Project Director (Multiple Project Proposal)
Completed Research Support
BOA #501-23-00 Crowell (PI)
VA Merit
Molecular Markers of Respiratory Carcinogenesis in Sputum
12/1/99 – 11/30/04
This project will establish a cohort of cigarette smokers with chronic airflow obstruction and determine the reproducibility of detecting genetic aberrations in sputum from these subjects.
Role: Co-Investigator
1-RO1-CA88937 Schiller (PI)
NIH (subcontract through Univ. Wisconsin)
7/1/01 – 6/30/05
CCNU in NSCLC Patients with Methylation of the MGMT Gene
The objective of this project is to test the hypothesis that patients with advanced NSCLC and aberrant MGMT methylation will be sensitive to the nitrosourea CCNU.
Role: Co-Investigator; Principal Investigator of subcontract
1-RO1-CA089551-01 Belinsky (PI) 6/1/01 – 5/31/07
NIH/NCI
Gene Methylation and Therapeutic Response in Lung Cancer
The goal of these studies is to determine whether specific genes inactivated by promoter hypermethylation can be detected in sputum and/or plasma for cancer diagnosis. In addition, the predictive value for survival in persons with advanced non-small cell lung cancer who are positive for these methylation changes will be determined.
Role: Principal Investigator
RO1-CA95568-01 Supplement
NIH
Belinsky (PI) 5/1/04 – 1/31/08
Biomarkers to Assess Selenium Chemoprevention from NSCLC
To conduct cell culture and animal studies evaluating the ability of selenium combination with inhibitors of histone deacetylase to inhibit cell growth and lung tumor prevention.
Role: Principal Investigator
R01-ES008801-06 Belinsky (PI)
NIH
Tumor Suppressor Gene Methylation in Lung Adenocarcinoma
2/1/06 – 12/31/10
To conduct laboratory studies to identify gene methylation profiles in adenocarcinoma from smokers and never smokers and to identify important factors involved in transcriptional silencing through effects on the cytosine and histone code.
Role: Principal Investigator
RO1-CA95568 ARA Competitive Supplement Belinsky (PI)
NIH
9/1/09 – 10/31/11
Biomarkers to Assess Selenium Chemoprevention from NSCLC
To assess the effect of a demethylating agent and a histone deacetylase inhibitor on lung tumor growth and reprogramming of the epigenome in a nude rat orthotopic model.
Role: Principal Investigator