Lu-Chang, A-Lien - University of Maryland-Baltimore - Department of Biochemistry and Molecular Biology

个人简介

Dr. Lu-Chang received her Bachelor and Master degrees from National Taiwan University and Ph. D. from the University of North Carolina – Chapel Hill. She then completed her post-doctoral work at Duke University in the Department of Biochemistry. In 1984, she joined the faculty of the University of Maryland Medical School as an assistant professor of Biochemistry & Molecular Biology. She was subsequently promoted to associate professor with tenure in 1990 and professor in 1997. Dr. Lu-Chang became a member of the Program in Oncology, University of Maryland Greenebaum Cancer Center in 1994. She holds one patent from the United States Patent Office, and has been continuously funded as a principal investigator since 1985.

研究领域

Dr. Lu-Chang is a member of the Molecular and Structural Biology Program within the University of Maryland Marlene and Stewart Greenebaum Cancer Center Program in Oncology. As such, she collaborates with both basic and clinical research investigators to identify candidate proteins that may serve as markers for malignancy and/or targets for new drugs. Dr. Lu-Chang’s research centers on the DNA repair, DNA damage response, and cancer biology. She has been studying DNA repair for over 30 years. Her lab is studying the interplays among DNA repair, DNA replication, cell cycle checkpoint, transcription, and chromatin remodeling. She has discovered the MutY base excision repair (BER) pathway in E. coli, fission yeast S. pombe, and mammalian cells. Her laboratory has shown that MutY glycosylase homolog (MYH) interacts with DNA replication enzymes (PCNA and RPA), mismatch repair enzymes (MSH2/MSH6), cell cycle checkpoint proteins (Rad9/Rad1/Hus1, the 9-1-1 complex) and an aging regulator (SIRT6). Figure 1 They have proposed that 9-1-1 serves as a platform to regulate BER repair (Fig. 1). These proteins are encoded by "care keeper" genes which maintain genomic stability. It has been shown that germline mutations in human MYH gene can lead to colorectal adenomatous polyposis (MYH-associated polyposis, MAP) while mutations in mismatch repair genes are associated with hereditary nonpolyposis colon cancer (HNPCC). Moreover, thymine DNA glycosylase(TDG), AP endonuclease (APE1), and 9-1-1 are essential for embryonic development.

近期论文

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Hwang, B. J., A. Madabushi, J. Jin, S.-Y. S. Lin, and A.-L. Lu. (2014). Histone/protein deacetylase SIRT1 is an aiticancer therapeutic target. Amer. J. Cancer Res. 4, 211-221. [PMID:24959376] Hwang, B. J., G. Shi, and A. L. Lu. (2014). Mammalian MutY homolog (MYH or MUTYH) protects cells from oxidative DNA damage. DNA Repair 13:10-21. [PMID: 24315136] Jin, J., B. J. Hwang, P. W. Chang, E. A. Toth, and A. L. Lu. (2014). Interaction of apurinic/apyrimidinic endonuclease 2 (Apn2) with Myh1 DNA glycosylase in fission yeast. DNA Repair 15:1-10. [PMID: 24559510] Luncsford, P. J., B. A. Manvilla, D. N. Patterson, S. S. Malik, J. Jin, B. J. Hwang, R. Gunther, S. Kalvakolanu, L. J. Lipinski, W. Yuan, W. Lu, A. C. Drohat, A.-L. Lu, and E. A. Toth. (2013). Coordination of MYH DNA glycosylase and APE1 endonuclease activities via physical interactions. DNA Repair 12:1043-1052. [PMID: 24209961] Madabushi, A., B. J. Hwang, J. Jin, and A. L. Lu. (2013). Histone deacetylase SIRT1 modulates and deacetylates DNA base excision repair enzyme thymine DNA glycosylase. Biochem. J. 456:89-98. [PMID: 23952905] Shi, G., D.-Y. Chang, C. C. Cheng, X. Guan, C. Venclovas and A-L. Lu (2006). Physical and functional interactions between MutY glycosylase homologue (MYH) and checkpoint proteins Rad9-Rad1-Hus1. Biochem J. 400: 53-62. [PMID:16879101] Guan, X., A. Madabushi, D.-Y. Chang, M. E. Fitzgerald, G. Shi, A. C. Drohat, and A-L. Lu (2007). The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates DNA repair enzyme TDG glycosylase. Nucleic Acids Res. 35, 6207-6218. [PMID:17855402] Guan, X., H. Bai, G. Shi, C. A. Theriot, T. K. Hazra, S. Mitra, and A-L. Lu (2007). The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase. Nucleic Acids Res., 35, 2463-2472. [PMID:17395641] Bai, H., A. Madabushi, X. Guan, and Lu, A-L. (2010). Interaction between human mismatch repair recognition proteins and checkpoint sensor Rad9-Rad1-Hus1. DNA Repair, 9, 478-487. [PMID:20188637] Bai, H., S. Grist, G. Suthers, T. M. Wilson and A-L. Lu (2006). Functional characterization of human MutY homolog (hMYH) missense mutation (R231L) that is linked with hMYH-associated polyposis. Cancer Lett. 250, 74-81. [PMID:17081686]