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Young-Sam Lee, PhD



  • Associate Professor

College Unit(s)

Biography and Education


B.S., Seoul National University, Korea M.S., Seoul National University, Korea M.S., Indiana University, Bloomington Ph.D., University of Chicago Postdoctoral; Harvard University


Abnormal metabolism is frequently associated with various human diseases, including cancer, diabetes, and neurodegenerative diseases, among others. Abnormal metabolism is not only a consequence of these diseases but also an essential feature necessary for the progression of diseases. However, it is still unclear how abnormal metabolism contributes to various diseases. We hypothesize that abnormal metabolism, at least in parts, contributes to human diseases by generating false metabolic signals. The goal of my laboratory is to identify metabolic signalings contributing to human diseases. For this purpose, we identified several protein-metabolite interactions initiating metabolic signaling cascades. We study metabolic signaling in human diseases using a combination of (1) protein biochemistry, (2) biophysical analysis of protein-metabolite interactions, (3) mass spectrometric identification of novel protein-metabolite interactions, (4) characterization of the signaling in cultured mammalian cells, (5) developing small molecule regulators of metabolic signaling, and (6) small animal experiments.

Selected Publications

Park JS, Gabel AM, Kassir P, Kang L, Chowdhary PK, Osei-Ntansah A, Tran ND, Viswanathan S, Canales B, Ding P, Lee YS, Brewster R. (2022) N-myc downstream regulated gene 1 (ndrg1) functions as a molecular switch for cellular adaptation to hypoxia. eLife. DOI: 10.7554/eLife.74031.

Connor B, Titialii-Torres K, Rockenhaus AE, Passamonte S, Morris AC, Lee YS* (2022) Biliverdin regulates NR2E3 and zebrafish retinal photoreceptor development. Sci. Rep. DOI: 10.1038/s41598-022-11502-3.

Shon H, Matveeva EA, Jull EC, Hu Y, Coupet TA, Lee YS*. (2022) Evience supporting substrate channeling between domains of human PAICS: a time-course analysis of 13C-bicarbonate incorporation. Biochemistry 61(7):575-582 [PMID:35285625] [PMC8988938]

Lee JH, Mosher EP, Lee YS, Bumpus NN, Berger JM. (2022) Control of topoisomerase II activity and chemotherapeutic inhibition by TCA cycle metabolites. Cell Chem Biol 29(3): 476-489 [PMID: 34529934]

Yan M, Chakravarthy S, Tokuda JM, Pollack L, Bowman GD*, & Lee YS* (2016) Succinyl-5-aminoimidazole-4-carboxamide-1-ribosse 5′-Phosphate (SAICAR) activates pyruvate kinase isoform M2 (PKM2) in its dimeric form. Biochemistry 55(33) 4731-4736 [PMID: 27481063]

Kim J, Xiao H, Koh J, Wang Y, Bonanno JB, Thomas K, Babbitt PC, Brown S, Lee YS, & Almo SC. (2015) Determinants of the ComB carboxymethyl transferase utilized for selective tRNA wobble modification. Nucleic Acids Research 43(9), 4602-4613 [PMCID: PMC4482062]

Keller KE, Doctor ZM, Dwyer ZW, & Lee YS*. (2014) SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells. Molecular Cell 53(5), 700-709. [PubMed] [PMC] [Journal].

Kim J, Xiao H, Bonanno JB, Kalyanaraman C, Brown S, Tang X, Patskovsky Y, Babbitt PC, Jacobson MP, Lee YS, & Almo SC. (2013) Structure-guided discovery of the metabolite carboxy-SAM that modulates tRNA function. Nature 498, 123-126. [PMC3895326].

Keller KE, Tan IS, & Lee YS*. (2012) SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions. Science 338, 1069-1072. [PubMed] [PMC] [Journal].

Lee YS, Huang K, Quiocho FA, & O’Shea EK. (2008) Molecular basis of cyclin-CKD-CKI regulation by reversible binding of an inositol pyrophosphate. Nature Chemical Biology 4, 25-32 [PMC2367112]. 

Lee YS, Mulugu S, York JD, & O’Shea EK. (2007) Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphate. Science 316, 109-112 [PMC2211727]. 

Lee YS, Bergson P, He WS, Mrksich M, and Tang WJ. (2004) Discovery of a small molecule that inhibits the interaction of anthrax edema factor with its cellular activator: calmodulin. Chemistry & Biology 11, 1139-1146 

Guo Q, Shen YQ, Lee YS, Gibbs CS, Mrksich M, and Tang WJ. (2005) Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin. EMBO J. 24, 3190-3201 [PMC1224690]

Soelaiman S, Wei BQ, Bergson P, Lee YS, Shen Y, Mrksich M, Shoichet BK, and Tang WJ. (2003) Structure-based inhibitor discovery against adenylyl cyclase toxins from pathogenic bacteria that cause anthrax and whooping cough. J. Biol. Chem. 278, 25990-25997 [PMID: 12676933]

Shen Y, Lee YS, Soelaiman S, Bergson P, Lu D, Chen A, Beckingham K, Grabarek Z, Mrksich M, and Tang WJ. (2002) Physological calcium concentrations regulate calmodulin binding and catalysis of adenylyl cyclase exotoxins. EMBO J. 21, 6721-6732 [PMC139101]

Lee YS and Mrksich M. (2002) Protein chips: from concepts to practice. Trends Biotechnol. 20, S14-S18 [PMID: 12570154]

Hodneland CD, Lee YS, Min DH, and Mrksich M. (2002) Selective immobilization of proteins to self-assembled monolayers presenting active-site directed capture ligands. Proc. Natl. Acad. Sci. USA 99, 5048-5052 [PMC122719].

Lee YS, Gurnon DG, Hollenbeck JJ, and Oakley MG. (2001) Selection of a high-affinity DNA pool for a bZip protein with an out-of-phase alignment of the basic region relative to the leucine zipper. Bioorg. Med. Chem. Lett. 9, 2335-2339 [PMID: 11553473]

Suh J, Lee Y, and Han S. (2000) Activation and stabilization of chymotrypsin in microdomain of poly (ethylene-imine) derivatives. Bioorg. Med. Chem. 8, 1331-1336 [PMID: 9871761]


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