Moon-Shong Tang, PhD

For the past forty years I have been working on finding the mechanisms of how the two most important environmental agents – tobacco smoke and sunlight – induce carcinogenesis.  My focus has been in identifying the nature of the DNA damage induced by these carcinogens, the DNA damage distribution in the p53 tumor suppressor gene and ras oncogenes, and the relationship between DNA damage and mutations.  In collaboration with Dr. Gerd Pfeifer, Beckman Institute at City of Hope,  we have developed UvrABC incision and ligation-mediated PCR to map DNA damage at sequence level which enables us to achieve these goals. 

For the past ten years my research has been on determining the health effect of electronic-cigarette aerosols (ECA), nicotine and cotinine.  We have found that E-cig, nicotine and cotinine induce two carcinogenic effects: induction of g-OH-propano-dG and O⁶-methyl-dG and inhibition of DNA repair in mice and human cells.   Most significantly, we have found that ECA induces lung adenocarcinoma (LUAD) in mice.  

We also found that nicotine and cotinine ehanace SARS-CoV-2 infection via different paths, and ECA causes lung injury. 

We are current deciphering the mutation signature and cancer driver genes in E-cig-induced ULAD.  It takes two decades for a tobacco smoker to develop lung cancer.  E-cig becomes popular less than twenty years.  Therefore, we expect that E-cig related lung cancer will emerge in the coming decade.  We anticipate our findings will serve as a paradigm for E-cig related lung cancer in humans and the information will be important for managing this new disease. 

We have found that ECA also induce mainly bladder urothelial hyperplasia in mice.  These results indicate that E-cig is not a complete bladder carcinogen.  In collaboration with Dr. Xue-Ru Wu, Urology Department, we are currently determining the role of p53 and H-ras mutations, chromosome deletions, and urothelial wounds in E-cig-induced bladder carcinogenesis.

Relevant Publications

1. Denissenko, M.F., Pao, A., Tang*, M.-s. and Pfeifer*, G.P.  Preferential formation of benzo[a]pyrene adduct at lung cancer mutation hotspots in p53. Science, 274: 430-432, 1996. (* Corresponding authors)
2. Feng, Z., Hu, W., HU, Y. and Tang, M.-s. Acrolein Is A Major Cigarette-Related Lung Cancer Agent. Preferential Binding at p53 Mutational Hotspots and 

inhibition of DNA Repair. Proc. Natl. Acad. Sci. USA, 103, 15404-15409, 2006

1. Hsiang-Tsui Wang, Bongkun Choi, and Moon-shong Tang.   Melanocytes are deficient in repair of oxidative DNA damage and UV-induced photoproducts. Proc.             Natl. Acad. Sci. USA, 107, 180-185, 2010.
2. Lee HW, Park SH, Weng MW, Wang HT, Huang WC, Lepor H, Wu XR, Chen LC, Tang MS. E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. Proc Natl Acad Sci U S A,115:E1560-E1569, 2018.
3. Tang MS, Wu XR, Lee HW, Xia Y, Deng FM, Moreira AL, Chen LC, Huang WC, Lepor L. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc Natl Acad Sci U S A. 116:21727-21731, 2019.
4. Peng G, Xi Y, Bellini C, Pham K, Zhuang ZW, Yan Q, Jia M, Wang G, Lu L, Tang MS, Zhao H, Wang H. Nicotine dose-dependent epigenomic-wide DNA methylation changes in the mice with long-term electronic cigarette exposure. Am J Cancer Res. 2022 Aug 15;12(8):3679-3692. PMID: 36119846; PMCID: PMC9442002.
5. M.M. Marques, et al., Carcinogenicity of acrolein, crotonaldehyde, and arecoline, .Lancet Oncol. 22 (1) (2021) 19–20, doi:10.1016/S1470-2045(20)30727-0.

Grant support

1. P01CA165980   Molecular Tumorigenesis of Bladder Cancer.
2. Lung Cancer Discovery Award from American Lung Association.  Title: E-cigarette smoke induced lung carcinogenesis.