My research interests are to elucidate the cellular and molecular mechanisms by which environmental carcinogens cause lung cancer and to identify markers for the diagnosis, prognosis and treatment of this disease. We investigate genetic and epigenetic changes in oncogenes and tumor suppressor genes in specimens obtained from lung cancer patients and individuals at high risk for developing lung cancer. In addition, we apply new mouse models to investigate pathways of tobacco smoke carcinogen-mediated lung tumorigenesis. We would like to understand how airway epithelial cells are involved in the initiation and progression of lung tumors, and how they are influenced by environmental factors that increase lung cancer risk and how they respond to therapies.
Undergraduate
1974-1976 Louis Pasteur University Diploma of General Studies
Strasbourg, France Nature and Life Sciences
1976-1977 Louis Pasteur University Bachelor of Sciences
Strasbourg, France Structural and Metabolic
Chemistry and Organic Chemistry
1977-1978 Louis Pasteur University Master's Degree
Strasbourg, France Microbiology, Physico-Chemical
and Molecular Biology
1978-1979 Louis Pasteur University Diploma of Advanced Study
Strasbourg, France Biochemistry and Molecular Biology
Graduate
1979-1982 Louis Pasteur University University Doctorate
Strasbourg, France Biochemistry and Molecular Biology
1982-1986 Louis Pasteur University Doctorate of Sciences
Strasbourg, France Biochemistry and Molecular Biology
Post Graduate
1986-1988 Massachusetts Institute of Postdoctoral Fellow Technology, Cambridge Molecular Toxicology
MA 02139
Membership in professional and scientific societies
- Environmental Mutagen Society
- American Association for Cancer Research
- Society of Toxicology
Teaching:
Previously taught courses:
EOH 2371 Cellular and Molecular Toxicology 2 credits
EOH 2303 Applications of Molecular Methods to Toxicology
(Lab. Class)
Group teaching (ongoing)
EOH 2310 Molecular Fundamentals: Cell cycle control, apoptosis and cancer
(student presentation)
Keohavong, P., Lan, Q., Gao W. (2018) Mutat. Res., 829-830: 70-74. doi: 10.1016/j.mrgentox.2018.03.010. Epub 2018 Mar 30
Gao, W.M., Zhu, D., Keohavong, P. (2017) Sequence-dependent cleavage of mismatched DNA by Ban I restriction endonuclease. J Mol Recognit., Oct; 30 (10). doi: 10.1002/jmr.2638. Pub 2017 May 4.
Gao, W.M.,Jin, J., Yin, J., Land S., Gaither-Davis, A, Christie, N., Luketich, J.D., Siegfried, J., Keohavong, P. (2017) KRAS and TP53 mutations in bronchoscopy samples from former lung cancer patients. Mol. Carcinogenesis, 56: 381-388.
Gao W, Lu C, Chen L, Keohavong P. Overexpression of CRM1 (2015): A Characteristic Feature in a Transformed Phenotype of Lung Carcinogenesis and a Molecular Target for Lung Cancer Adjuvant Therapy. J Thorac Oncol. 2015;10(5):815-825
Shvedova AA, Yanamala N, Kisin ER, Tkach AV, Murray AR, Hubbs A, Chirila MM, Keohavong P, Sycheva LP, Kagan VE, Castranova V. Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons. Am J Physiol Lung Cell Mol Physiol. 2014;306(2):L170. PPMID: 24213921. PMCID:PMC3920208.Stabile LP, Rothstein ME, Cunningham DE, Land SR, Dacic S, Keohavong P, Siegfried JM. Prevention of tobacco carcinogen-induced lung cancer in female mice using antiestrogens. Carcinogenesis. 2012 Nov;33(11):2181-9. PMID:22859269. PMCID:PMC3584962.
Keohavong P, Kahkonen B, Kinchington E, Yin J, Jin J, Liu X, Siegfried JM, DI YP. K-ras mutations in lung tumors from NNK-treated mice with lipopolysaccharide-elicited lung inflammation. Anticancer research. 2011 Sep;31(9):2877-82. PMID:21868532.
Shvedova AA, Kisin E, Murray AR, Johnson VJ, Gorelik O, Arepalli S, Hubbs AF, Mercer RR, Keohavong P, Sussman N, Jin J, Yin J, Stone S, Chen BT, Deye G, Maynard A, Castranova V, Baron PA, Kagan VE. Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice:
inflammation, fibrosis, oxidative stress, and mutagenesis. American journal of physiology. Lung cellular and molecular physiology. 2008 Oct;295(4):L552-65. PMID:18658273. PMCID:PMC2575941.
Stabile LP, Rothstein ME, Keohavong P, Jin J, Yin J, Land SR, Dacic S, Luong TM, Kim KJ, Dulak AM, Siegfried JM. Therapeutic targeting of human hepatocyte growth factor with a single neutralizing
monoclonal antibody reduces lung tumorigenesis. Molecular cancer therapeutics. 2008 Jul;7(7):1913-22. PMID:18645002. PMCID:PMC2556508.
Liu Y, Gao W, Siegfried JM, Weissfeld JL, Luketich JD, Keohavong P. Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers. BMC cancer. 2007;7:74. PMID:17477876. PMCID:PMC1877812.
Gao WM, Romkes M, Siegfried JM, Luketich JD, Keohavong P. Polymorphisms in DNA repair genes XPD and XRCC1 and p53 mutations in lung carcinomas of never-smokers. Molecular carcinogenesis. 2006 Nov;45(11):828-32. PMID:16865671.
Zhang W, Stabile LP, Keohavong P, Romkes M, Grandis JR, Traynor AM, Siegfried JM. Mutation and polymorphism in the EGFR-TK domain associated with lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2006 Sep;1(7):635-47. PMID:17409930.
Liu Y, Lan Q, Siegfried JM, Luketich JD, Keohavong P. Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients. Neoplasia (New York, N.Y.). 2006 Jan;8(1):46-51. PMID:16533425. PMCID:PMC1584289.
Keohavong P, Xi L, Day RD, Zhang L, Grant SG, Day BW, Ness RB, Bigbee WL. HPRT gene alterations in umbilical cord blood T-lymphocytes in newborns of mothers exposed to tobacco smoke during pregnancy. Mutation research. 2005 May 2;572(1-2):156-66. PMID:15790499.
Keohavong P, Lan Q, Gao WM, Zheng KC, Mady HH, Melhem MF, Mumford JL. Detection of p53 and K-ras mutations in sputum of individuals exposed to smoky coal emissions in Xuan Wei County, China. Carcinogenesis. 2005 Feb;26(2):303-8. PMID:15564291.
Lan Q, Mumford JL, Shen M, Demarini DM, Bonner MR, He X, Yeager M, Welch R, Chanock S, Tian L, Chapman RS, Zheng T, Keohavong P, Caporaso N, Rothman N. Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions. Carcinogenesis. 2004 Nov;25(11):2177-81. PMID:15284179.
Gao WM, Romkes M, Siegfried JM, Luketich JD, Keohavong P. No association between the XPD 312, 751, or XRCC1 399 polymorphisms and K-ras gene mutation in smoking non-small-cell lung cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2004 Apr;13(4):673-5. PMID:15066937.
Gao WM, Romkes M, Day RD, Siegfried JM, Luketich JD, Mady HH, Melhem MF, Keohavong P. Association of the DNA repair gene XPD Asp312Asn polymorphism with p53 gene mutations in tobacco-related non-small cell lung cancer. Carcinogenesis. 2003 Oct;24(10):1671-6. PMID:12844488.
Gao WM, Mady HH, Yu GY, Siegfried JM, Luketich JD, Melhem MF, Keohavong P. 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 histologic types. Lung cancer (Amsterdam, Netherlands). 2003 May;40(2):141-50. PMID:12711114.
DeMarini DM, Landi S, Tian D, Hanley NM, Li X, Hu F, Roop BC, Mass MJ, Keohavong P, Gao W, Olivier M, Hainaut P, Mumford JL. Lung tumor KRAS and TP53 mutations in nonsmokers reflect exposure to PAH-rich coal combustion emissions. Cancer research. 2001 Sep 15;61(18):6679-81. PMID:11559534.
Keohavong P, Mady HH, Gao WM, Siegfried JM, Luketich JD, Melhem MF. Topographic analysis of K- ras mutations in histologically normal lung tissues and tumors of lung cancer patients. British journal of cancer. 2001 Jul 20;85(2):235-41. PMID:11461083. PMCID:PMC2364035.
Gealy R, Zhang L, Siegfried JM, Luketich JD, Keohavong P. Comparison of mutations in the p53 and K-ras genes in lung carcinomas from smoking and nonsmoking women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 1999 Apr;8(4 Pt 1):297-302.
PMID:10207632.
Zhu D, Keohavong P, Finkelstein SD, Swalsky P, Bakker A, Weissfeld J, Srivastava S, Whiteside TL. K-ras gene mutations in normal colorectal tissues from K-ras mutation-positive colorectal cancer patients. Cancer research. 1997 Jun 15;57(12):2485-92. PMID:9192830.
Keohavong P, Zhu D, Melacrinos AC, DeMichele MA, Weyant RJ, Luketich JD, Testa JR, Fedder M, Siegfried JM. Detection of low-fraction K-ras mutations in primary lung tumors using a sensitive method. International journal of cancer. 1997 Apr 22;74(2):162-70. PMID:9133449.
Przygodzki RM, Finkelstein SD, Keohavong P, Zhu D, Bakker A, Swalsky PA, Soini Y, Ishak KG, Bennett WP. Sporadic and Thorotrast-induced angiosarcomas of the liver manifest frequent and multiple point mutations in K-ras-2. Laboratory investigation; a journal of technical methods and pathology. 1997 Jan;76(1):153-9. PMID:9010458.
Keohavong P, DeMichele MA, Melacrinos AC, Landreneau RJ, Weyant RJ, Siegfried JM. Detection of K-ras mutations in lung carcinomas: relationship to prognosis. Clinical cancer research : an official journal of the American Association for Cancer Research. 1996 Feb;2(2):411-8. PMID:9816185.
Keohavong P, Thilly WG. Mutational spectrometry: a general approach for hot-spot point mutations in selectable genes. Proceedings of the National Academy of Sciences of the United States of
America. 1992 May 15;89(10):4623-7. PMID:1584799. PMCID:PMC49135.
Keohavong P, Thilly WG. Fidelity of DNA polymerases in DNA amplification. Proceedings of the National Academy of Sciences of the United States of America. 1989 Dec;86(23):9253-7. PMID:2594764. PMCID:PMC298472.
Cariello NF, Scott JK, Kat AG, Thilly WG, Keohavong P. Resolution of a missense mutant in human genomic DNA by denaturing gradient gel electrophoresis and direct sequencing using in vitro DNA amplification: HPRT Munich. American journal of human genetics. 1988 May;42(5):726-34. PMID:3358423. PMCID:PMC1715170.
Schmitt P, Gattoni R, Keohavong P, Stévenin J. Alternative splicing of E1A transcripts of adenovirus requires appropriate ionic conditions in vitro. Cell. 1987 Jul 3;50(1):31-9. PMID:2954651.
Keohavong P, Gattoni R, Schmitt P, Stévenin J. The different intron 2 species excised in vivo from the E2A pre-mRNA of adenovirus-2: an approach to analyze alternative splicing. Nucleic acids research. 1986 Jul 11;14(13):5207-27. PMID:3737399. PMCID:PMC311536.
Gattoni R, Keohavong P, Stévenin J. Splicing of the E2A premessenger RNA of adenovirus serotype 2. Multiple pathways in spite of excision of the entire large intron. Journal of molecular biology. 1986 Feb 5;187(3):379-97. PMID:3009832.
Stévenin J, Gattoni R, Keohavong P, Jacob M. Mild nuclease treatment as a probe for a non-random distribution of adenovirus-specific RNA sequences and of cellular RNA in nuclear
ribonucleoprotein fibrils. Journal of molecular biology. 1982 Mar 5;155(3):185-205. PMID:6281447.
Keohavong P, Gattoni R, LeMoullec JM, Jacob M, Stévenin J. The orderly splicing of the first three leaders of the adenovirus-2 major late transcript. Nucleic acids research. 1982 Feb 25;10(4):1215-29. PMID:6175954. PMCID:PMC320520.
