Research Assistant Professor - Biochemistry, Macromolecular Chemistry, and Biophysical Chemistry
Research and/or Creative Works
Our group is interested in understanding the kinetics and fundamental molecular mechanisms that underlie the search for DNA damage by DNA repair enzymes. Because these search processes are highly dynamic and heterogeneous, we utilize single-molecule fluorescence microscopy techniques (time-resolved fluorescence microscopy, optical trap microscopy) to observe individual enzymes as they scan along DNA tightropes in real time. We are continually developing new single molecule methodology, and students in the laboratory have the opportunity to gain expertise in the areas of fluorescence imaging and optics, statistical analysis of single particle trajectories, methods for surface patterning, enzymology, creative DNA cloning and construction, enzyme structural analyses, and genome database mining. By applying these methods to the study of human cancer variants, we are also exploring how search deficiencies may contribute to carcinogenesis and other disease.
Lee AJ, Majumdar C, Kathe SD, Van Ostrand RP, Vickery HR, Averill AM, Nelson SR, Manlove AH, McCord MA, David SS. "Detection of OG:A Lesion Mispairs by MutY Relies on a Single His Residue and the 2-Amino Group of 8-Oxoguanine." J. Am. Chem. Soc, 2020, 142(31), 13283–13287
Drost M, Tiersma Y, Glubb D, Kathe S, van Hees S, Calleja F, Zonneveld JBM, Bouche KM, Ramlal RP, Thompson BA, Rasmussen LJ, Greenblatt MS, Lee AJ, Spurdle AB, Tavtigian SV, de Wind N. “Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch Syndrome.” Genetics in Medicine, 2020, 22, 847-856
Nelson SR, Kathe SD, Hilzinger TS, Averill AM, Warshaw DM, Wallace SS, Lee AJ “Single molecule glycosylase studies with engineered 8-oxoguanine DNA damage sites show functional defects of a MUTYH polyposis variant.” Nucleic Acids Res. 2019, 47(6), 3058-3071
Lee AJ, Warshaw DM, Wallace SS. “Insights into the Glycosylase Search for Damage from Single-molecule Fluorescence Microscopy (review).” DNA Rep. 2014, 20, 23-31.
Lee AJ, Asher WB, Ensign AA, Stern HA, Bren KL, Krauss TD. "Single-Molecule Analysis of Cytochrome C Folding by Monitoring the Lifetime of an Attached Fluorescent Probe.” J. Phys. Chem. Lett. 2013, 4, 2727-2733.
Lee AJ, Wang X, Carlson LJ, Smyder JA, Tu X, Zheng M, and Krauss TD. “Bright Fluorescence from Individual Single-Walled Carbon Nanotubes.” Nano Lett. 2011, 11, 1636-1640.
Lee AJ, Ensign AA, Bren KL, and Krauss TD. “Zinc Porphyrin as a Donor for FRET in Zn(II)cytochrome c.” J. Am. Chem. Soc. 2010, 132, 1752-1753.
Associations and Affiliations
Microbiology and Molecular Genetics (Primary Appointment)
Department of Chemistry (Secondary Appointment)
Cellular, Molecular, and Biomedical Sciences Program
Areas of Expertise and/or Research
Single molecule fluorescence microscopy. Molecular mechanisms of DNA repair. Single particle tracking. Dynamics of protein-DNA interactions.
- Ph.D. Chemistry — University of Wisconsin-Madison, 2007
- B.A. Chemistry — Northwestern University
- (802) 656-0816