PROFESSIONAL EXPERIENCE
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 Description
Current interests in my laboratory are DNA mismatch repair, protein-DNA interactions, telomere-length regulation, and carcinogenesis. Mismatch repair is an error avoidance pathway devoted to enhancing the fidelity of DNA replication. Mutations in human repair genes could lead to genetic instability in cancer. We have studied a specific pathway in both prokaryotes and eukaryotes for repairing A/G, A/8-oxoG, and A/C mismatches. The E. coli MutY protein, the key enzyme involved in this pathway, has been shown to have both DNA glycosylase and 3' apurinic/apyrimidinic (AP) lyase activities. 8-oxoG is the major oxidative damage to DNA, so MutY corrects the errors that result from the replication of DNA containing oxidative damage. Repair mechanism by which the MutY recognizes its substrates is currently studied.

We have identified the homologs of E. coli MutY (MYH) in yeast, human HeLa and calf thymus nuclear extracts. Both human and calf systems share similar features with the E. coli mutY-dependent pathway. Mismatch repari mechanism in yeast and human systems will be studied. Yeast and human cDNA of MYH will be expressesd in E. coli and protein activities will be assayed. Yeast mutants defective in the MYH and the mutation rate will be measured. The linkage of MYH repair to cancer are currently pursued. Human lung cancer cells or patients will be screened for the mutation in hMYH gene and enzyme activities will be analyzed. A new reliable and sensitive method using covalent binding of MutY to heteroduplex DNA for detecting G:C to T:A mutations in disease and cancer diagnosis will be explored. Through the study of the mechanism of DDNA mismatch repair, our understanding of cancer, aging, and genetic disease can be advanced. We have detected and partially characterized a novel ribonucleoprotein enzyme, called endonuclease Y, from extracts of calf thymus and human cells. This enzyme, in the absence of Mg2+, cleaves guanine-rich duplex DNA sequences, including the vertebrate telomere sequence (5'TTAGGG3'), to generate products with 3' phosphate groups. Endonuclease Y may play a role in telomere-length regulation and cell senescence.

Selected Publications:
Lu, A-L., Lee C.-Y., Li, L., Li, X. H. Physical and functional interactions between Escherichia coli MutY and endonuclease VIII. Biochem J. in press.

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.