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Lei Li, Ph.D.

  

Education

  • B.S., Peking University, 1996 
  • M.S., Peking University, 1999 
  • Ph.D., Johns Hopkins University, 2005
  • Postdoctoral Fellow, University of Michigan, 2005-09

Courses Taught / Teaching

  • C696 "Special Topics in Protein Structure & Function " (Fall)
  • C430 "Inorganic Chemistry" (Spring)
  • C435 "Inorganic Chemistry Laboratory" (Spring)

Research

Mechanistic studies of DNA repair enzyme spore photoproduct lyase (SPL)

Endospore-forming bacteria are responsible for a number of serious diseases in humans, including anthrax and botulism. Infectious endospores are extremely resistant to a number of harsh environments. Their unusual tolerance to high-dose UV irradiation arises from the action of spore photoproduct lyase (SPL) - a metalloenzyme that repairs the "spore photoproduct" dithymine DNA lesion. SPL uses a 5'-deoxyadenosyl (5'-dA) radical, formed from reductive cleavage of S-adenosylmethionine (SAM), to initiate lesion repair, but little else is known about its mechanism. The objectives of the project are: (1) To understand the photochemistry of thymine damage. We will employ thymine and its analogs to explore the influence on the reaction rates/yields. (2) To identify critical SPL-substrate interactions. We will evaluate SP repair in different DNA local environments. (3) To reveal the detailed reaction mechanism. We will measure the deuterium isotope effect to shed light on the reaction energy surface, examine reaction reversibility, and probe the radical intermediates with various mechanism-based inhibitors. (4) To understand the radical initiation reaction in SPL. We will determine the redox potential of the unique [Fe4S4] cluster, coupled with key amino acids mutagenesis studies.

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Publications & Professional Activities

Setlow, P. & Li, L. "Photochemistry and Photobiology of the spore photoproduct, a fifty year journey", Photochem. Photobio., 2015, 1263-1290. (Invited review, selected as cover story and featured article)

Jian, Y.; Lin, G.; Chomicz, L.; & Li, L. "Reactivity of Damaged Pyrimidines: Formation of a Schiff base intermediate at the glycosidic bond of saturated dihydrouridine", J. Am. Chem. Soc. 2015, 3318-3329.

Jian, Y.; Ames, D. M.; Ouyang, H.; & Li, L. "Photochemical reactions of microcrystalline thymidine", Org. Lett. 2015, 824-827.

Yang, L. & Li, L., "The spore photoproduct lyase: the known, the controversial and the unknown" (Invited minireview), J. Biol. Chem. 2015, 4003-4009.

Lin, G.; Jian, Y.; Ouyang, H.; & Li, L. "An unexpected deamination reaction after hydrolysis of the pyrimidine (6-4) pyrimidone photoproduct", Org. Lett., 2014, 16(19), 5076-5079.

Lin, G.; Jian, Y.; Dria, K. J.; Long, E. C.; & Li, L. "Reactivity of Damaged Pyrimidines: DNA Cleavage via Hemiaminal Formation at the C4 Positions of the Saturated Thymine of Spore Photoproduct and Dihydrouridine", J. Am. Chem. Soc., 2014, 136, 12938-12946.

Ames, DM, Lin,G. Jian, Y., Cadet, J., & Li, L., "Unusually large deuterium discrimination during spore photoproduct formation", J. Org. Chem. 2014, 79 (11), 4843-4851. (chosen as a featured article by editor)

Singh I.; Lian, Y.; Li, L.; Georgiadis, M.M. "The structure of an authentic spore photoproduct lesion in DNA suggests a basis for recognition", Acta. Crystallogr. D. Biol. Crystallogr., 2014, 752-759.

 Yang, L.; Nelson, R. S.; Benjdia A.; Lin, G.; Telser, J.; Stoll, S.; Schlichting I.; & Li, L. "A radical transfer pathway in the spore photoproduct lyase", Biochemistry, 2013, 3041-3050. (recommended by Faculty of 1000 Prime)

Lin, G. & Li, L. "Oxidation and reduction of the 5-(2'-deoxyuridinyl)methyl radical", Angew. Chem. Int. Ed., 2013, 5594-5598.

G. Lin and L. Li "Elucidation of spore-photoproduct formation by isotope labeling" Angewandte Chemie, Int. Ed. Engl. 2010, 9926-9929. (chosen as a "Hot Paper" by the editors).

Professional Affiliations

  • Member, The American Chemical Society

Honors, Awards and Grants

  • NSF Career Award 2015-2020
  • NIH Pathway to Independence Award (K99/R00) 2008-2013