Principal Investigator/Program Director (Last, First, Middle):
Keohavong Phouthone
BIOGRAPHICAL SKETCH
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NAME
POSITION TITLE
Keohavong Phouthone
Associate Professor
eRA COMMONS USER NAME
pho1
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as
nursing, and include postdoctoral training.)
DEGREE
INSTITUTION AND LOCATION
(if
YEAR(s)
FIELD OF STUDY
applicable)
University Louis Pasteur, Strasbourg, France
M.S.
1979
Biochemistry
University Louis Pasteur, Strasbourg, France
Ph.D.
1986
Biochem./Molec.Biology
Massachusetts Institute of Technology
Post-doct.
1988
Molecular Toxicology
A. Positions and Honors.
Positions and Employment
1986-1988: Postdoctoral fellow, Massachusetts Institute of Technology, Cambridge, MA
1988-1991: Research Scientist, Massachusetts Institute of Technology, Cambridge, MA
1991-2000: Assistant Professor, Department of Environmental and Occupational Health, University of
Pittsburgh, Pittsburgh, PA
2001-Present: Associate Professor, Department of Environmental and Occupational Health, University of
Pittsburgh, Pittsburgh, PA
Other Experience and Professional Memberships
1987-Present: Member, Environmental Mutagen Society
1995-Present: Member, American Association for Cancer Research
1997-Present: Member, Society of Toxicology
2002-2004: Member, Advisory Board of the International Society for Preventive Oncology
2002-2004: Member, Grant Panel, FAMRI, American Institute of Biological Sciences
B. Selected peer-reviewed publications (in chronology order). (Publication selected from 52 peer-reviewed
publications)
1. Keohavong, P., and Thilly, W.G.: Mutational Spectrometry: A general approach to detect point mutations in
selectable genes Proc. Natl. Acad. Sci. USA. (1992), 89,4623-4627.
2. Cha, R.S., Zabl, H., Keohavong, P., and Thilly, W.G.: Mismatch Amplification Mutation Assay (MAMA):
Application to the c-H-ras Gene in Rat Mammary. PCR: Methods and Applications. (1992) 2: 14-20.
3. Shvedova, A.A., Kramarik, J.A., Keohavong, P., Chumakov, K.M. and Karol, M.H.: Use of anti-TNF-a
antiserum to investigate toxic alveolitis arising from cotton dust exposure in mice. Exp. Lung Res., (1994)
20: 297-315.
4. Keohavong, P., DeMichelle, M.A.A., Melacrinos, A.C., Landreneau, R.J., Weyant, R.J. and Siegfried, J.M.:
Detection of K-ras mutations in lung carcinomas: Relationship to prognosis. Clinical Cancer Research
(1996) 2: 411-418.
5. Przygodski, R.M., Finkelstein, S.D., Keohavong, P., Zhu, D., Bakker, A., Swalsky, P.A., Soini, Y., Ishak, K.G.
and Bennett, W.P. Sporadic and thorothrast-induced angiosarcomas of the liver manifest frequent and
multiple point mutations in K-ras-2. Lab. Investigation (1997). 76: 153-159.
6. Keohavong, P., Zhu, D., Whiteside, T.L., Swalsky, P., Bakker, A, Elder, E.M., Siegfried, J.M., Srivastava, S.
and Finkelstein, S.D. Detection of infrequent and multiple mutations in human tumors and tumor-adjacent
tissues. Anal. Biochem.(1997) 247: 394-403.
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Principal Investigator/Program Director (Last, First, Middle):
Keohavong Phouthone
7. Keohavong, P., Zhu, D., Melacrinos, A.C., DeMichelle, M.A.A., Weyant, R.J., Luketich, J.D., Testa, J.R.,
Fedder, M, and Siegfried, J.M. Detection of low fraction K-ras mutations in primary lung tumors using a
sensitive method. Int. J. Cancer (1997) 74: 162-170.
8. Zhu, D., Keohavong, P., Finkelstein, S. D., Swalska, P., Bakker, A., Weissfeld, J., Srivastava, S. and
Whiteside, T. L. K-ras mutations in normal colorectal tissues from K-ras mutation-positive colorectal cancer
patients (1997) Cancer Research, 57: 2485-2492.
9. Siegfried J.M., Gillespie, A.T., Mera, R., Casey, T.J., Keohavong, P. and Hunt J.D.Prognostic values of
specific K-ras mutations in lung adenocarcinomas. Cancer Epidemiology Biomarkers and Prevention
(1997) 6: 841-847.
10. Gealy, R., Zhang, L.F., Siegfried, J.M., Luketich, J.D. and Keohavong, P. Comparison of K-ras and p53
gene mutations in smoking and non-smoking women with lung cancer. Cancer Epidemiology Biomarkers
and Prevention, (1999) 8: 297-302.
11. DeMarini, D.M., Landi, S., Tian, D., Hanley, N.M., Li,X., Hu.F., Roop, B.C., Mass, M.J., Keohavong, P.,
Gao, W.M., Olivier, M., Hainaut, P. and Mumford, J.(2001) Lung tumor KRAS and TP53 mutations in
nosmokers reflects exposure to PAH-rich coal combustion emissions. Cancer Res., 61: 6679-6681.
12. Keohavong, P., Maddy, H.H., Gao, W-.M., Siegfried, J.M., Luketich, J.D., Melhem, M.D. (2001)
Topographic analysis of K-ras mutations in histologically normal lung tissues and tumors of lung cancer
patients. British Journal of Cancer, 85: 235-241.
13. Keohavong, P., Lan, G., Gao, W.M., DeMarini, D.M., Mass, J.M., Li, X.M., Roop, B.C., Weissfeld, J., Tian,
D., and Mumford, J.L. (2003). Mutations in the K-ras gene in lung carcinomas from nonsmoking women
exposed to unvented coal smoke in China. Lung Cancer, 41: 21-27.
14. Zhang, L.F., Gao W.M., Elders, E., Weissfeld, J., Whiteside, T., and Keohavong, P. (2003) Comparison of
K-ras gene mutations in tumor and sputum DNA of patients with lung cancer. Biomarkers, 8:156-161.
15. Gao, W.M., Mady, H., Yu, G.Y., Siegfried, J., Luketich, J.D., Melhem, M.F. and Keohavong, P.(2003)
Comparison of p53 mutations between adenocarcinoma and squamous cell carcinoma of the lung: Unique
spectra involving G to A transitions and G to T transversions in both types. Lung Cancer, 40:141-150.
16. Gao, W.M., Romkes, M., Day, R.D., Siegfried, J.M., Luketich, J.D., Mady, H.H., Melhem, M.F. and
Keohavong, P. (2003) Association of the DNA repair gene XPD Asp312Asn polymorphism with p53 gene
mutations in tobacco-related non-small-cell lung cancer. Carcinogenesis, 24: 1671-1676.
17. Keohavong, P., Gao, W-M., Zheng, K-C., Hussam, M., Qing, L., Mona, M., and Mumford, M. (2003)
Detection of K-ras and p53 Mutations in Sputum Samples of Lung Cancer Patients Using Laser Capture
Microdissection Microscope and Mutation Analysis. Anal. Biochem.,324: 92-99.
18. Gao, W.M., Romkes, M., Siegfried, J.M., Luketich, J.D. and Keohavong, P. (2004) No association between
the XPD Asp 312, 751, or XRCC1 399 polymorphisms and K-ras gene mutations in smoking non-small-cell
lung cancer. Cancer Epidemiol. Biomarkers & Prev., 13: 673-675.
19. Lan, Q., Mumford, J., Shen, M., DeMarini, D.M., Bonner, M.R., He, X., Yeager, M., Welch, R., Chanock, S.,
Tian, L., Chapman, R.S., Zheng, T., Keohavong, P., Caporaso, N., and Rothman, N. (2004) Oxidative
damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich
coal combustion emissions. Carcinogenesis, 25: 2177 - 2181.
20. Keohavong, P., Lan, Q., Gao, W-M., Zheng, K.C., Mady, H.H., Melhem, M.F. and Mumford, J.L. (2005).
Detection of p53 and K-ras mutations in sputum of individuals exposed to smoky coal emissions in Xuan
Wei county, China. Carcinogenesis, 26: 303-308.
21. Lan, Q., Shen, M., Berndt, S.I., Bonner, M.R., Heb, X., Yeager, M., Welch, R., Keohavong, P., Donahue,
M., Hainaut, P. and , Chanock, S. (2005). Smoky coal exposure, NBS1 polymorphisms, p53 protein
accumulation, and lung cancer risk in Xuan Wei, China. Lung Cancer, 49317-49323.
22. Liu, Y., Lan, Q., Siegfried, J.M., Luketich, J.D. and Keohavong, P. (2006) Aberrant promoter methylation of
p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients. Neoplasia, 8:
48-51.
23. Zhang, W., Stabile, L.P., Keohavong, P., Romkes, M., Grandis, J.R., Schiller, J.H., Traynor, A.M., and
Siegfried, J.M. (2006). Mutation of K-ras and p53 and polymorphism in the EGFR-TK Domain associated
with Lung Cancer. J. Thoracic Oncology, 1(7): 635-647.
24. Gao WM, Romkes M, Siegfried JM, Luketich JD, Keohavong P. (2006) Polymorphisms in DNA repair
genes XPD and XRCC1 and p53 mutations in lung carcinomas of never-smokers. Mol Carcinog., 45: 828832
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Principal Investigator/Program Director (Last, First, Middle):
Keohavong Phouthone
C. Research Support
Ongoing Research Support
RSG-99-161-04-CNE
Keohavong (PI)
01/01/04 - 12/31/07
American Cancer Society
K-ras and p53 mutations in bronchoscopy samples as biomarkers for Lung Cancer in former smokers
The major goal of this proposal is to test the hypothesis that K-ras and p53 mutations and microsatellite
instabilities occur frequently in bronchoscopy tissues and bronchoalveolar lavage samples obtained from
former lung cancer patients who no longer show evidence of lung cancer, and may provide biomarkers for the
diagnosis of lung cancer recurrence in these individuals.
Role: PI
2RO1 CA59834-06 B. Branch (PI)
07/01/01 - 6/30/05
NIH
Drug Metabolizing Enzymes and Risk Factors in Bladder Cancer
The major goal of this proposal is to apply knowledge of pharmacogenomic implications of gene expression of
individual drug metabolizing enzymes to assess their role as risk markers for bladder cancer.
Role: Co-Investigator
1RO1 CA90787-01 J. Yalowich (PI)
07/01/01 - 6/30/05
NIH
Mechanisms and prevention of etoposide-induced leukemia
The major goal of this proposal is to determine the precise mechanism(s) by which activation of VP-16 to free radic
enhances its DNA damaging activity specifically in genomic regions of the MLL gene known to contain breakpoint as
with t-AML.
Role: Co-Investigator
Completed Research Support
RPG-99-161-CNE
Keohavong (PI)
07/01/99 – 06/30/03
K-ras and p53 mutations as biomarkers for lung cancer
The goal of this study was to assess the role of K-ras and p53 mutations as biomarkers for lung cancer
diagnosis and prognosis by investigating these mutations in lung tumor and matched histologically-normal lung
tissues, sputum, and plasma obtained from lung cancer patients and individuals at high-risk for lung cancer.
Role: PI
R827151
Fabisiak (PI)
07/01/98 – 06/30/00
Environmental Protection Agency
Chemical mixture in Environmental Health
The major goal of this proposal was to elucidate the role of metallothioneins in protecting against or enhancing
oxidative stress upon exposure to transition metal/heavy metal mixtures or transition metal/nitric oxide
mixtures.
Role: Co-Investigator
1RO1 HD33016-01A1
Bigbee (PI)
08/01/1996 – 07/30/01
NIH
Lifestyle Factors Affecting Fetal Somatic Mutations
The major goal of this proposal was to determine whether maternal exposure to tobacco smoke and
socioeconomic status result in a detectably increased levels of mutant frequencies and specific spectra at the
HPRT gene locus.
Role: Co-Investigator
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Principal Investigator/Program Director (Last, First, Middle):
PHS 398/2590 (Rev. 09/04)
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Keohavong Phouthone
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