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A-Lien  Lu-Chang

A-Lien Lu-Chang Ph.D.

Academic Title: Professor
Primary Appointment: Biochemistry and Molecular Biology
Location: Biomedical Research Facility, Room 337
Phone: (410) 706-4356
Fax: (410) 706-1787
Lab: (410) 706-4355

Personal History:


1971: B. S., Botany, National Taiwan University, Taiwan
1973: M. S., Plant Physiology, National Taiwan University, Taiwan
1980: Ph.D., Biochemistry, University of North Carolina at Chapel Hill.

Post Graduate Education

1980-1984: Postdoctoral Fellow, Duke University, Durham, North Carolina

Employment History

1973-1974: Research Assistant, National Taiwan University, Department of Botany.
1974-1976: Teaching Assistant and Laboratory Instructor, National Taiwan University, Department of Botany.
1980-1984: Research Associate, Duke University, Department of Biochemistry.
1984-1990: Assistant Professor, University of Maryland, Baltimore, Department of Biological Chemistry.
1990-1997: Associate Professor, University of Maryland, Baltimore, Department of Biological Chemistry.
1997-present: Professor, University of Maryland, Baltimore, Department of Biological Chemistry.
1988-present: Faculty member of Molecular and Cell Biology Graduate Program, University of Maryland at Baltimore.
1990-present: Member, University of Maryland Greenebaum Cancer Center

Research Interests:

Current interests in my laboratory are DNA repair, protein-DNA interactions, protein-protein interactions, and carcinogenesis. Defects in DNA repair can lead to genome instability, a hallmark of cancer. We are studying lesion-specific DNA glycosylases involved in the base excision repair (BER) pathway recognizing a large variety of spontaneous and induced DNA lesions. Bacterial MutY and eukaryotic MYH are adenine glycosylases which remove adenines from A/G, A/8-oxoG, and A/C mismatches. 8-oxoG is the abundant and highly mutagenic oxidative damage to DNA, so MutY corrects the errors that result from the DNA replication. Bacterial mutY and yeast MYH mutants have a mutator phenotype. Germline mutations in the human MYH gene are associated with autosomal recessive colorectal adenomatous polyposis. NEIL1 and OGG1 glycosylases are involved in the repair of DNA lesions derived from oxidative damage. The CpG dinucleotide is highly susceptible to mutation, contributing approximately 30% of germline mutations. Human TDG and MBD4 (Med1) play a central role in the cellular defense against deamination and the toxicity of methylating agents. Human TDG also removes the cytotoxic anti-cancer agent 5-fluouracil as well as exocyclic bases induced by environmental pollutants. The important of TDG and MBD4 has been demonstrated that TDG knockout mice are embryonic lethal and Mbd4 knockout mouse cells failed to undergo cell cycle arrest and apoptosis after stress treatments.

Our recent findings show that MYH is directly linked to DNA replication via proliferating cell nuclear antigen (PCNA) and replication protein A (RPA), to mismatch repair via hMSH6, to BER pathway via AP endonuclease (APE1), and to cell cycle checkpoint control via Hus1/Rad1/Rad9 (the 9-1-1 complex). The MYH glycosylase activity is stimulated by MSH2/MSH6, APE1, and the 9-1-1 complex. We have also shown that the 9-1-1 complex interacts with and stimulates TDG, MBD4, NEIL1, and OGG1 glycosylases as well as MSH2/MSH6 mismatch repair enzyme. Our finding of the interactions of the 9-1-1 complex with DNA repair enzymes support a model that damage recognition proteins are adaptors for checkpoint sensor proteins to activate damage response. Mammalian cell cycle checkpoints have been recognized as key tumor-suppressor mediators that prevent the accumulation of mutation that drives carcinogenesis. It has been shown that targeted deletion of many murine checkpoint genes, including Hus1, Rad9, and Rad17, resulted in embryonic lethality. Our recent findings indicate a new role of the 9-1-1 complex. At the lesion sites, the complex not only serves as a damage sensor to activate checkpoint control but is also a component of BER, and may act as a platform for the different factors involved in BER.

Through the study of the mechanism of DNA mismatch repair, our understanding of cancer, aging, and genetic diseases can be advanced. Such knowledge may have implications for treating human disease and cancer because DNA glycosylases can confer tumor cells with increased resistance to anticancer drugs that target DNA. Thus, DNA glycosylases and checkpoint proteins are potentially attractive targets for cellular sensitization to anticancer drugs.

Laboratory Personnel:

  • Dau-Yin Chang, Assistant Professor
  • Powen Chang, Post Doctoral Fellow
  • Xin Guan, Post Doctoral Fellow
  • Gouli Shi, Post Doctoral Fellow
  • Min Gao, Laboratory Technician
  • Nai-Yun Hsu, Laboratory Technician
  • Haibo Bai, Graduate Student


Bai, H., Grist, S., Suthers, G., Wilson, T. M., & Lu, A-L. Functional characterization of human MutY homolog (hMYH) missense mutation (R231L) that is linked with hMYH-associated polyposis. Cancer Lett. 250: 74-81. 2007.

Bai, H. & Lu, A-L. Physical and functional interaction between Escherichia coli MutY glycosylase and mismatch repair protein MutS. J. Bacteriol. 189: 902-910. 2007.

Guan, X., Bai, H., Shi, G., Theriot, C. A., Hazra, T. K., Mitra, S., & Lu, A-L. The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase. Nucleic Acids Res. 35: 2463-2472. 2007.

Guan, X., Madabushi, A., Chang, D.-Y., Fitzgerald, M. E., Shi, G., Drohat, A. C., & Lu, A-L. The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates DNA repair enzyme TDG glycosylase. Nucleic Acids Res. 35, 6207-6218. 2007.

Lu, A-L., Bai, H., Shi, G., & Chang D.Y. MutY and MutY homologs (MYH) in genome maintenance. Front. Biosci. 11, 3062-3080. (2006).

Shi, G., Chang, D.-Y., Cheng, C. C., Guan, X., Venclovas, C. & Lu, A-L. Physical and functional interactions between MutY glycosylase homoloque (MYH) and checkpoint proteins Rad9-Rad1-Hus1. Biochem J. 400: 53-62. 2006.

Bai, H., Jones, S., Guan, X., Wilson, T. M., Sampson, J. R., Cheadle, J. P., & Lu, A-L. Functional characterization of two human MutY homolog (hMYH) missense mutations (R227W and V232F) that lie within the putative hMSH6 binding domain and are associated with hMYH polyposis. Nucl. Acids. Res. 33: 597-604. 2005.

Gu, Y. S., Parker, A., Wilson, T. M., Bai, H., Chang, D.-Y., & Lu, A-L. Human MutY homolog (hMYH), a DNA glycosylase involved in base excision repair, physically and functionally interacts with mismatch repair proteins hMSH2/hMSH6. J. Biol. Chem. 277: 11135-11142. 2002.

Chang, D.-Y., & Lu, A-L. Functional interaction of MutY homolog (MYH) with proliferating cell nuclear antigen (PCNA) in fission yeast, Schizosaccharomyces pombe. J. Biol. Chem. 277: 11853-11858. 2002.

Lu, A-L. & Wright P. M. Characterization of an Escherichia coli mutant MutY with a cysteine to alanine mutation at the iron-sulfur cluster domain. Biochemistry 42: 3742-3750. 2003.

Li, L. & Lu, A-L. The C-terminal domain of Escherichia coli MutY is involved in DNA binding and glycosylase activities. Nucl. Acids. Res. 31: 3038-3049. 2003.