Chen, Yu - University of South Florida - Morsani College of Medicine

个人简介

Education 1993-1997 B.S., Biochemistry and Molecular Biology Peking University, Beijing, China. 1997-2002 Ph.D., Biochemistry and Molecular Biology University of Chicago, Dept. of Biochemistry and Molecular Biology Advisor: Dr. Phoebe A. Rice Experience 2003 Postdoctoral Fellow University of Chicago, Dept. of Biochemistry and Molecular Biology Advisor: Dr. Phoebe A. Rice 2003-2009 Postdoctoral Fellow University of California, San Francisco, Dept. of Pharmaceutical Chemistry Advisor: Dr. Brian K. Shoichet 2009-2015 Assistant Professor University of South Florida, Dept. of Molecular Medicine 2010-present Member H. Lee. Moffitt Cancer Center and Research Institute 2015-present Associate Professor University of South Florida, Dept. of Molecular Medicine 2016-present Associate Professor University of South Florida, Dept. of Internal Medicine 2016-present Associate Professor University of South Florida, Dept. of Cell Biology, Microbiology and Molecular Biology Honors and Awards 2015 Robert J. Grasso Award for Outstanding Dedication to Graduate Education, USF 2015 Excellence in Innovation Award, USF

研究领域

The Chen lab (http://www.thechenlab.com) focuses on structure-based drug design against proteins involved in infectious diseases and cancer. We utilize a multi-disciplinary approach, combining biochemistry, structural biology and computational chemistry, to investigate the function and inhibition of enzymes related to bacterial cell wall synthesis, the biological process targeted by antibiotics such as penicillin. We also study human signal transduction proteins in collaboration with other laboratories. Our research goals include: Studying molecular interactions at atomic and ultimately subatomic scale through ultra-high resolution X-ray crystallography; Developing fragment-based molecular docking for drug discovery; Identifying novel inhibitors as potential drug leads and chemical probes for proteins of biomedical importance.

近期论文

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Lewandowski, E.M., Szczupak, Ł., Kowalczyk, A., Mendoza, G., Arruebo, M., Jacobs, L.M.C., Stączek, P., Chen, Y., Kowalski, K. (2020) Metallocenyl 7-ACA Conjugates: Antibacterial Activity Studies and Atomic-Resolution X-ray Crystal Structure with CTX-M β-Lactamase. ChemBioChem. In press Hecker, S.J., Reddy, K.R., Lomovskaya, O., Griffith, D.C., Rubio-Aparicio, D., Nelson, K., Tsivkovski, R., Sun, D., Sabet, M., Tarazi, Z., Parkinson, J., Totrov, M., Boyer, S.H., Glinka, T.W., Pemberton, O.A., Chen, Y., Dudley, M.N. (2020) Discovery of Cyclic Boronic Acid QPX7728, an Ultra-broad-spectrum Inhibitor of Serine and Metallo Beta-lactamases. J. Med. Chem. In press. O’Flynn, B.G., Lewandowski, E.M., Prins, K.C., Suarez, G., McCaskey, A.N., Rios-Guzman, N.M., Anderson, R.L., Shepherd, B.A., Gelis, I., Leahy, J.W., Chen, Y., Merkler, D.J. (2020) Characterization of Arylalkylamine N-Acyltransferase from Tribolium castaneum: An Investigation into a Potential Next-Generation Insecticide Target. ACS Chem. Biol. 15(2):513-23 Pemberton, O.A., Noor, R.E., Kumar M.V., V., Sanishvili, R., Kemp. M.T., Kearns, F.L., Woodcock, H.L., Gelis, I., Chen, Y. (2020) Mechanism of proton transfer in class A β-lactamase catalysis and inhibition by avibactam. Proc. Natl. Acad. Sci. 117(11):5818-25 Pennington, J.M., Kemp, M., McGarry, L., Chen, Y., Stroupe, M.E. (2020) Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site. Nat. Commun. 11(1):864 Akhtar, A., Pemberton, O.A., Chen, Y. (2020) Structural basis for substrate specificity and carbapenemase activity of OXA-48 Class D β-lactamase. ACS Infect Dis. 6(2):261-271 Sacco, M.D., Kroeck, K.G., Kemp, M.T., Zhang, X., Andrews, L.D., Chen, Y. (2019) Influence of the α-methoxy group on the reaction of temocillin with Pseudomonas aeruginosa PBP3 and CTX-M-14 β-lactamase. Antimicrob. Agents Chemother. 64(1): e01473-19. Kim, M.Y., Na, I., Kim, J.S., Son, S.H., Choi, S., Lee, S.E., Kim, J.H., Jang, K., Alterovitz, G., Chen, Y., van der Vaart, A., Won, H., Uversky, V.N., Kim, C.G. (2019) Rational discovery of antimetastatic agents targeting the intrinsically disordered region of MBD2. Sci. Adv. 5(11): eaav9810. Kroeck, K.G., Sacco, M.D., Smith, E.W., Zhang, X., Shoun, D., Akhtar, A., Darch, S.E., Cohen, F., Andrews, L.D., Knox, J.E., Chen, Y. (2019) Discovery of dual-activity small-molecule ligands of Pseudomonas aeruginosa LpxA and LpxD using SPR and X-ray crystallography. Sci. Rep. 9(1):15450. Woo, J.A., Castaño, M., Goss, A., Kim, D., Lewandowski, E.M., Chen, Y., Liggett, S.B. (2019) Differential long-term regulation of TAS2R14 by structurally distinct agonists. FASEB J. 33(11):12213-25. Pemberton, O.A., Jaishankar, P., Akhtar, A., Adams, J.L., Shaw, L.N., Renslo, A.R., Chen, Y. (2019) Heteroaryl phosphonates as non-covalent inhibitors of both serine and metallo-carbapenemases. J. Med. Chem. 62(18):8480-96. DeFrees, K., Kemp, M. Trent, ElHilali-Pollard, X., Zhang, X., Mohamed, M., Chen, Y., Renslo, A. R. (2019) An Empirical Study of Amide–Heteroarene π-Stacking Interactions Using Reversible Inhibitors of a Bacterial Serine Hydrolase. Org. Chem. Front. 6, 1749-1756. Torelli, N.J., Akhtar, A., DeFrees, K., Jaishankar, P., Pemberton, O.A., Zhang, X., Johnson, C., Renslo, A.R., Chen Y. (2019) Active-Site Druggability of Carbapenemases and Broad-Spectrum Inhibitor Discovery. ACS Infect Dis. 5(6):1013-1021. Pemberton, O.A., Zhang, X., Nichols, D.A., DeFrees, K., Jaishankar, P., Bonnet, R., Adams, J., Shaw, L.N., Renslo, A.R., Chen, Y. (2018) Antibacterial Spectrum of a Tetrazole-Based Reversible Inhibitor of Serine β-Lactamases. Antimicrob. Agents Chemother. 62(8): e02563-17. Lewandowski, E.M., Lethbridge, K.G., Sanishvili, R., Skiba, J., Kowalski, K., Chen, Y. (2018) Mechanisms of proton relay and product release by Class A β-lactamase at ultrahigh resolution. FEBS J. 285(1):87-100. Dempsey, D.R., Nichols, D.A., Battistini, M.R., Pemberton, O., Ospina, S.R., Zhang, X., Carpenter, A.M., O’Flynn, B.G., Leahy, J.W., Kanwar, A., Lewandowski, E.M., Chen, Y.*, Merkler, D.J.*. (2017) Structural and Mechanistic Analysis of Drosophila melanogaster Agmatine N-Acetyltransferase, an Enzyme that Catalyzes the Formation of N-Acetylagmatine. Sci Rep. 7(1):13432. (*co-corresponding author) Pemberton, O.A., Zhang, X., Chen, Y. (2017) Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2). J. Med. Chem. 60(8):3525-30. Lewandowski, E.M., Szczupak, L., Wong, S., Skiba, J., Guśpiel, A., Solecka, J., Vrcek, V., Kowalski, K., Chen, Y. (2017). Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase. Organometallics. 36(9):1673-76. Smith, E.W., Lewandowski, E.M., Moussouras, N.A., Kroeck, K.G., Volkman, B.F., Veldkamp, C.T., Chen, Y. (2016) Crystallographic structure of truncated CCL21 and putative sulfotyrosine-binding site. Biochemistry. 55(40):5746-53. Smith, E.W., Nevins, A.M., Qiao, Z., Liu, Y., Getschman, A.E., Vankayala, S.L., Kemp, M.T., Peterson, F.C., Li, R., Volkman, B.F., Chen, Y. (2016) Structure-Based Identification of Novel Ligands Targeting Multiple Sites within a Chemokine-G-Protein-Coupled-Receptor Interface. J. Med. Chem. 59(9):4342-51. Smith, E.W., Zhang, X., Behzadi, C., Andrews, L.D., Cohen, F., Chen, Y. (2015) Structures of Pseudomonas aeruginosa LpxA reveal basis for substrate selectivity. Biochemistry. 54(38):5937-48.