Zhang, Xin - The Pennsylvania State University

个人简介

Education Ph.D. Chemistry, California Institute of Technology, 2010 M.S. Chemistry, Dalian Institute of Chemical Physics, the Chinese Academy of Sciences, 2004 B.S. Chemistry, University of Science and Technology of China, 2001 Honors and Awards CAPA Distinguished Junior Faculty Award, 2020 NSF CAREER, 2020 NIGMS-MIRA, 2019 Pew Biomedical Scholar, 2019 The Scialog Fellow, 2018 The Sloan Research Fellowship, 2018 The Lloyd and Dottie Huck Early Career Award, 2015-16 The Burroughs Wellcome Fund Career Award at the Scientific Interface, 2014-19 American Chemical Society National Award – Nobel Laureate Signature Award for Graduate Education in Chemistry, 2012 The Damon Runyon Cancer Research Fellowship Award, 2011 (declined) The Helen Hay Whitney Fellowship Award, 2011-14 (selected as a Howard Hughes Medical Institute Fellow) Springer Thesis Award, 2010 Herbert Newby McCoy Award of Caltech, 2010 Chinese Government Award for Outstanding Self-financed Students Abroad, 2009 The Ulric B. and Evelyn L. Bray Endowment Fellowship, 2006-08 Distinguished Thesis Award in Liaoning Province, China, 2005 The Liu Yonglin Award, 2000

研究领域

The main focus is protein misfolding and aggregation that occur in stressed cells with deficient proteostasis. These molecular events have been associated with a variety of diseases that are termed as protein misfolding diseases. Protein aggregation is a multiple step process that involves misfolded soluble and insoluble aggregates. It is unclear which of these conformations could lead to cytotoxicity that is associated with diseases. To tackle this question, our lab develops innovative chemical methodologies that allow the community to visualize and differentiate, in live cells and organisms, the many conformations through the process of protein aggregation. We combine expertise from synthetic chemistry, in vitro biochemistry and cell biology. The ultimate goal is not only to provide a tool set for the community, but also to define (in live cells) biochemical nature of species in protein aggregation and their mechanism of action in disease initiation and progression. Currently, we attempt to address the following questions: 1) How can we detect and differentiate various conformational species during protein aggregation in live cells and organisms? 2) How can we quantify proteostasis deficiency during cellular stress? 3) How can we detect and understand misfolding and aggregation of intrinsically-disordered proteins, represented by a class of RNA-binding proteins (RBPs) that harbor prion-like domains, in membrane-less organelles? 4) How can we develop small molecules that could prevent misfolding and aggregation, if any, of RBPs in membrane-less organelles?

近期论文

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S. Ye, H. Zhang, J. Fei, C. Wolstenholme and X. Zhang*, “A general strategy to control viscosity sensitivity of molecular rotor-based fluorophores”, Angew. Chem. Int. Ed., in press. C.H. Wolstenholme, H. Hu, S. Ye, B.E. Funk‡, D. Jain‡, C.-H. Hsiung, G. Ning, Y. Liu*, X. Li* and X. Zhang*, “AggFluor: Fluorogenic toolbox enables direct visualization of the multi-step protein aggregation process in live cells”, J. Am. Chem. Soc., 142 (2020), 17515–17523.(highlighted by JACS Spotlights, Protein Aggregation: It’s a Process) C.A. Hoelzel and X. Zhang*, “Visualizing and manipulating biological processes using Halo-Tag and SNAP-Tag technologies“, ChemBioChem, 21 (2020), 1935-1946. K.H. Jung and X. Zhang*, “Fluorogenic detection of protein aggregates in live cells using the AggTag method“, Meth. Enzymol., 639 (2020), 1-22. C.A. Hoelzel, H. Hu, C.H. Wolstenholme, B.A. Karim‡, K.T. Munson, K. Jung, Y. Liu, H.P. Yennawar, J.B. Asbury, X. Li* and X. Zhang*, “A general strategy to enhance donor-acceptor molecules using solvent-excluding substituents“, Angew. Chem. Int. Ed., 59 (2020), 4785-4792. S.H. Kim, Y. Liu, C. Hoelzel, X. Zhang* and T.-H. Lee*, “Super-resolution optical lithography with DNA“, Nano Letter, 19 (2019), 6035-6042. Featured by Nat. Chem., Super-resolution writing. K.H. Jung, S.F. Kim‡, Y. Liu and X. Zhang*, “A fluorogenic AggTag method based on Halo- and SNAP-tag to simultaneously detect the aggregation of two proteins in live cells“, ChemBioChem, 20 (2019), 1078-1087. Part of the ChemBioTalents Special Issue. K.H. Jung, M. Fares, L.S. Grainger, C.H. Wolstenholme, A. Hou‡, Y. Liu and X. Zhang*, “A SNAP-tag fluorogenic probe mimicking the chromophore of the red fluorescent protein Kaede“, Org. Biomol. Chem., 17 (2019), 1906-1915. Part of the New Talent Special Issue. Y. Liu, M. Fares and X. Zhang*, “Monitoring proteome stress in live cells using HaloTag-based fluorogenic sensor”, Methods Mol. Biol., 1873 (2019), 171-182. M. Fares and X. Zhang*, “Quantification of cellular proteostasis in live cells using the AgHalo sensors“, Curr. Protoc. Chem. Biol., 2018:e58. H. Hu, C.H. Wolstenholme, X. Zhang* and X.S. Li*, “Inverted solvatochromic stokes shift in GFP-like chromophores with extended conjugation“, Chin. J. Chem. Phys., 31 (2018), 599-607. Y. Liu, K. Miao‡, Y. Li, M. Fares, S. Chen‡ and X. Zhang* “A HaloTag-based multi-color fluorogenic sensor visualizes and quantifies proteome stress in live cells using solvatochromic and molecular rotor-based fluorophores“, Biochemistry, 57 (2018), 4663-4674. Part of the Special Issue on Discovering New Tools. B.I. Leach, X. Zhang, J.W. Kelly, H.J. Dyson and P.E. Wright*, “NMR measurements reveal the structural basis of transthyretin destabilization by pathogenic mutations“, Biochemistry, 57 (2018), 4421-4430. Y. Liu, C.H. Wolstenholme, G. Carter, H. Liu, H. Hu, L.S. Grainger, K. Miao‡, M. Fares, C.A. Hoelzel, H. Yennawar, G. Ning, M. Du, L. Bai, X. Li and X. Zhang*, “Modulation of fluorescent protein chromophores to detect protein aggregation with turn-on fluorescence“, J. Am. Chem. Soc., 140 (2018), 7381-7384. A. Pedley, G. Karras, X. Zhang, S. Lindquist and S. Benkovic*, “The role of HSP90 in the regulation of de novo purine biosynthesis“, Biochemistry, 57 (2018), 3217-3221. X. Li, T. Wang, P. Duan, M. Baldini, H. Huang, B. Chen, S. Juhl, D. Koeplinger, V. Crespi, K. Schmidt-Rohr, R. Hoffmann, N. Alem, M. Guthrie, X. Zhang and J. Badding*, “Carbon nitride nanothread crystals derived from pyridine”, J. Am. Chem. Soc., 140 (2018), 4969-4972. Y. Liu and X. Zhang*, “Heat shock protein reports on proteome stress”, Biotechnology J, 13 (2018), 1800039.3. M. Fares, Y. Li, Y. Liu, K. Miao‡, Z. Gao‡, Y. Zhai‡ and X. Zhang*, “A molecular rotor-based Halo-tag ligand enables a fluorogenic proteome stress sensor to detect protein misfolding in mildly stressed proteome“, Bioconjutate Chem., 29 (2018), 215-224.2. Y. Liu, M. Fares, N. P. Dunham, Z. Gao‡, K. Miao‡, X. Jiang, S. S. Bollinger‡, A. K. Boal and X. Zhang*, “AgHalo: A facile fluorogenic sensor to detect drug induced proteome stress“, Angew. Chem. Int. Ed., 56 (2017), 8672-8676. Y. Liu, K. Miao‡, N.P. Dunham, H. Liu, M. Fares, X. Li, A.B. Boal and X. Zhang*, “The cation-π interaction enables a Halo-Tag fluorogenic probe for fast no-wash live cell imaging and gel-free protein quantification“, Biochemistry, 56 (2017), 1585-1595, (ACS Editor’s Choice). Featured by Viewpoint in Biochemistry.