个人简介

Ph.D., Massachusetts Institute of Technology, 2006 Pfizer Postdoctoral Fellow, The Scripps Research Institute (La Jolla), 2006 - 2010

研究领域

Chemical Biology and Biochemistry

Our research program applies chemical probes and mass spectrometry-based proteomics to investigate and perturb protein activities in complex proteomes. In particular, we focus on understanding the role of cysteine-mediated protein activities in cancer and degenerative diseases associated with aging. These activities comprise proteases, oxidoreductases and metabolic enzymes that rely on cysteine residues for catalysis and regulation. Functional cysteine residues demonstrate heightened reactivity relative to non-functional cysteines, and are sensitive to a myriad of oxidative protein modifications that serve to regulate protein activity in vivo. In cancer and age-related degenerative diseases, the cellular redox homeostasis is severely disrupted and the resulting oxidative stress can have dramatic consequences on cysteine-mediated protein activities. Through a multidisciplinary approach that encompasses aspects of synthetic chemistry, cell biology, proteomics and mass spectrometry, we will investigate the dysregulation of cysteine-mediated protein activities to identify therapeutic targets and small-molecule drug-leads for the diagnosis and treatment of diseases such as cancer.

近期论文

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Wei Y., Stec B., Redfield A.G., Weerapana E., Roberts M.F. Phospholipid binding sites of PTEN: Exploring the mechanism of PIP2 activation. J. Biol. Chem., 2015, in press. Bak D.W., Weerapana E. Cysteine-mediated redox signalling in the mitochondria. (Review) Molecular Biosystems, 2015, in press. Shannon D.A., Weerapana E. Covalent protein modification: the current landscape of residue-specific electrophiles. (Review) Current Opinion in Chemical Biology, 2015, 24, 18-26. Special issue on "Omics". Couvertier S.M., Zhou Y., Weerapana E. Chemical-Proteomic Strategies to Investigate Cysteine Posttranslational Modifications. (Review) Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2014, 1844, 2315-30. Tamburini, F., Kelly T., Weerapana E.*, Byers J.* Paper to Plastics: An interdisciplinary summer outreach project in sustainability. J. Chem. Ed., 2014, 91, 1574-79. Pace, N. J., Weerapana, E. Zinc-binding cysteines: diverse functions and structural motifs. (Review) Biomolecules, 2014, 4, 419-34. Special issue on "Metal-binding Proteins". Zhuang, J., Kuo, C.H., Chou, L.Y., Liu, D.Y., Weerapana, E.*, Tsung, C.K.* Optimized metal-organic-framework nanospheres for drug delivery: evaluation of small-molecule encapsulation. ACS Nano, 2014, 8, 2812-9. Shannon, D.A., Banerjee, R., Webster, E.R., Bak, D.W., Wang, C., Weerapana, E. Investigating the Proteome Reactivity and Selectivity of Aryl Halides J. Am. Chem. Soc., 2014, 136, 3330-3. Martell, J., Weerapana, E. Applications of copper-catalyzed click chemistry in activity-based protein profiling. (Review) Molecules, 2014, 19, 1378-93. Special Issue on "Bioorthogonal Chemistry" Wang, C., Weerapana, E., Blewett, M.M., Cravatt, B.F. A chemoproteomic platform to quantitatively map targets of lipid-derived electrophiles. Nature Methods, 2014, 11, 79-85. Couvertier, S. M., Weerapana, E. Cysteine-reactive chemical probes based on a modular 4-amino-piperidine scaffold. MedChemComm, 2014, 5, 358-62. Pace, N.J., Weerapana, E. A competitive chemical-proteomic platform to identify zinc-binding cysteines. ACS Chemical Biology, 2014, 9, 651-6. Shannon D.A., Weerapana, E. Orphan PTMs: Rare, yet functionally important modifications of cysteine. (Review) Biopolymers, 2014, 101, 156-64. Special issue on �The Next Frontier of Posttranslational Modifications Schwaid, A.G.#, Shannon, D.A.#, Ma, J., Slavoff, S.A., Levin, J.Z., Weerapana, E.*, Saghatelian, A.* Chemoproteomic discovery of cysteine-containing human short open reading frames. J. Am. Chem. Soc., 2013, 135, 16750-3. Child, M.A., Hall C.I., Beck, J.R., Ofori, L.O., Albrow,V.E., Garland, M., Bowyer, P.W., Bradley,P.J., Powers, J.C., Boothroyd, J.C., Weerapana, E., Bogyo, M. Small-molecule inhibition of a depalmitoylase enhances Toxoplasma host-cell invasion. Nat. Chem. Biol., 2013, 9, 651-6. Lee, B.C., P�terfi, Z., Hoffmann, F.W., Moore, R.E., Kaya, A., Avanesov, A., Tarrago, L., Zhou, Y., Weerapana, E., Fomenko, D.E., Hoffmann, P.R., Gladyshev, V.N. MsrB1 and MICALs Regulate Actin Assembly and Macrophage Function via Reversible Stereoselective Methionine Oxidation. Molecular Cell, 2013, 51, 397-404. Qian, Y., Martell, J., Pace N.J., Ballard, E.T., Johnson, D.S.*, Weerapana, E*. An isotopically tagged azobenzene-based cleavable linker for quantitative proteomics. ChemBioChem, 2013, 14, 1410-1414. Banerjee, R., Brown, D.R., Weerapana, E. Recent Developments in the Synthesis of Bioactive 2,4,6-Trisubstituted-1,3,5-Triazines. (Review) Synlett, 2013, 24, 1599-1605. Gu C., Shannon D.A., Colby T., Wang Z., Shabab M., Kumari S., Villamor J.G., McLaughlin C.J., Weerapana E., Kaiser M., Cravatt B.F., van der Hoorn R.A.L. Chemical Proteomics with Sulfonyl Fluoride Probes Reveals Selective Labeling of Functional Tyrosines in Glutathione Transferases. Chemistry & Biology, 2013, 20, 541-548. Deng X., Weerapana E., Ulanovskaya O., Sun F., Liang H., Ji Q., Ye Y., Fu Y., Zhou L., Li J., Zhang H., Wang C., Alvarez S., Hicks L.M., Lan L., Wu M., Cravatt B.F., He C. Proteome-wide Quantification and Characterization of Oxidation-Sensitive Cysteines in Pathogenic Bacteria. Cell Host Microbe, 2013, 13, 358-70.