Positions

Overview

  • As our understanding on the cell deepens, we appreciate more and more the sophisticated orchestration of cellular processes, where exchanges of protein components, addition and removal of posttranslational modifications take place in a highly ordered, dynamic manner. Since modern mass spectrometry excels in both characterization of protein complexes and elucidation of posttranslational modifications, we see a great opportunity to use and develop mass spectrometric techniques to shed light on those complex, dynamic cellular processes. In particular, we are interested in the molecular recognition among proteins in protein assemblies, the nature and function of posttranslational modifications in chromatin.

    Most cellular processes are carried out by protein assemblies, where strong protein interactions constitute stable architecture of the assemblies to ensure efficiency; while weak protein interactions regulate transient function of the assemblies to achieve plasticity. Conceivably, the molecular recognition among proteins dictates the organization, function and modulation of protein assemblies. We are interested in structural characterization of protein assemblies with an integrated chemical cross-linking and mass spectrometric approach. Chemical cross-linking of protein assemblies, followed by mass spectrometric identification of the cross-linked species provides valuable spatial constrains that can be used in conjunction with computational modeling to reveal surfaces involved in protein interactions. Since chemical cross-linking can covalently ‘lock’ various conformers in the conformational equilibrium of protein assemblies, we have used this approach to elucidate the structural dynamics of protein complexes. In addition, we are interested in developing mass spectrometric techniques to facilitate sensitive detection and confident identification of the cross-linked species. Thus far, we have developed tools and strategies that have proved robust for most binary complexes we have attempted. Equipped with these tools, we are expanding to the structural characterization of multi-subunit protein assemblies, a challenging domain yet to be tackled by this promising, integrative approach.

    The largest macromolecular assembly inside the cell might be chromatin, though little is known about its spatial organization. The function of structure alterations in chromatin is prominently manifested during the development of multi-cellular organisms, in which a variety of phenotypes are achieved from a singular genotype. As an epigenetic regulation mechanism, posttranslational modification of chromatin proteins can either recruit or exclude the binding of effector proteins to indirectly, or directly modulate chromatin structure. The ability for sensitive detection and specific structural elucidation, as well as the compatibility with upstream biochemical purification has made mass spectrometry ideal for the characterization of posttranslational modifications. We have developed a biochemical technique for rapid, one-step purification of large quantities of low abundance histone vairants and histone-associated proteins. Using this technique, we have elucidated multiple novel histone modifications. We are also interested in using comparative quantification during mass spectrometric analysis to elucidate dynamic changes in chromatin modifications. Quantitative profiling of chromatin modifications can serves as a starting point to study their function. Using a label-free quantitation strategy, we have revealed a significant increase in histone acetylation after UV irradiation, in concert with chromatin de-condensation and chromatin remodeling.
  • Publications

    Academic Article

    Year Title
    2019 Dynamic pigmentary and structural coloration within cephalopod chromatophore organs.Nature Communications.  10:1004. 2019
    2019 Comparative Phosphoproteomic Profiling of Type III Adenylyl Cyclase Knockout and Control, Male, and Female Mice.Frontiers in Cellular Neuroscience.  13:34. 2019
    2018 Chemical cross-linking in the structural analysis of protein assemblies.Methods Neuroprotocols.  144:53-63. 2018
    2017 An unfolded protein-induced conformational switch activates mammalian IRE1.eLife.  6:e30700. 2017
    2017 Genomic, transcriptomic, and proteomic approaches towards understanding the molecular mechanisms of salt tolerance in Frankia strains isolated from Casuarina trees.BMC Genomics.  18:633. 2017
    2017 An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5.Stem Cell Reports.  8:1488-1496. 2017
    2016 The epichaperome is an integrated chaperome network that facilitates tumour survival.Nature Nature: New biology.  538:397-401. 2016
    2016 Contributions of Phenoxazone-Based Pigments to the Structure and Function of Nanostructured Granules in Squid Chromatophores.Langmuir.  32:3754-3759. 2016
    2015 Molecular responses of Frankia sp. strain QA3 to naphthalene.Canadian Journal of Microbiology.  61:281-292. 2015
    2014 Molecular architecture of photoreceptor phosphodiesterase elucidated by chemical cross-linking and integrative modeling.Journal of Molecular Biology.  426:3713-3728. 2014
    2014 Copper tolerance in Frankia sp. strain EuI1c involves surface binding and copper transport.Applied Microbiology and Biotechnology.  98:8005-8015. 2014
    2014 Elucidating the mechanism of substrate recognition by the bacterial Hsp90 molecular chaperone.Journal of Molecular Biology.  426:2393-2404. 2014
    2013 Hdac6 regulates Tip60-p400 function in stem cells.eLife.  2:e01557. 2013
    2013 Probing the Structure of Photoreceptor Phosphodiesterase (PDE6) and Its Interactions with Transducin by Cross-linking and Molecular ModelingFASEB Journal.  27. 2013
    2013 Proteomic Identification of Preferential Interactions between PDE6 and its Inhibitory SubunitFASEB Journal.  27. 2013
    2013 Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5.Cell.  152:276-289. 2013
    2012 An orphan kinesin in trypanosomes cooperates with a kinetoplastid-specific kinesin to maintain cell morphology by regulating subpellicular microtubules.Journal of Cell Science.  125:4126-4136. 2012
    2012 Transcription factor binding to a DNA zip code controls interchromosomal clustering at the nuclear periphery.Developmental Cell.  22:1234-1246. 2012
    2011 Quantitative mass spectrometry reveals the epigenome as a target of arsenic.Chemico-Biological Interactions.  192:113-117. 2011
    2011 Identification of cyclophilin-40-interacting proteins reveals potential cellular function of cyclophilin-40.Analytical Biochemistry.  410:257-265. 2011
    2010 Finding chimeras: a bioinformatics strategy for identification of cross-linked peptides.Molecular and Cellular Proteomics.  9:25-31. 2010
    2010 The real Jurassic Park: the isolation of proteins from microorganisms preserved in amber inclusions for 40 million yearsExpert Review of Proteomics.  7:22. 2010
    2009 Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure.Toxicology and Applied Pharmacology.  241:294-302. 2009
    2009 The zinc finger protein Zn72D and DEAD box helicase Belle interact and control maleless mRNA and protein levels.BMC Molecular Biology.  10:33. 2009
    2008 Identification of a novel chromosomal passenger complex and its unique localization during cytokinesis in Trypanosoma brucei.PLoS ONE.  3:e2354. 2008
    2008 Histone acetylation and chromatin remodeling are required for UV-B-dependent transcriptional activation of regulated genes in maize.Plant Cell.  20:827-842. 2008
    2008 Human Proteinpedia enables sharing of human protein data.Nature Biotechnology.  26:164-167. 2008
    2007 Pkh-kinases control eisosome assembly and organization.EMBO Journal.  26:4946-4955. 2007
    2007 Hip is a pro-survival substrate of granzyme B.Journal of Biological Chemistry.  282:27865-27874. 2007
    2007 The site-specific installation of methyl-lysine analogs into recombinant histones.Cell.  128:1003-1012. 2007
    2006 Isotope-coded and affinity-tagged cross-linking (ICATXL): an efficient strategy to probe protein interaction surfaces.Journal of the American Chemical Society.  128:10362-10363. 2006
    2006 Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94.Protein Science.  15:1260-1269. 2006
    2006 Mapping post-translational modifications of the histone variant MacroH2A1 using tandem mass spectrometry.Molecular and Cellular Proteomics.  5:194-203. 2006
    2004 Unraveling the interface of signal recognition particle and its receptor by using chemical cross-linking and tandem mass spectrometry.Proceedings of the National Academy of Sciences of the United States of America.  101:16454-16459. 2004
    2002 Efficient Cs2CO3-promoted solution and solid phase synthesis of carbonates and carbamates in the presence of TBAITetrahedron.  58:3329-3347. 2002
    1999 Alkyl Carbonates: Efficient Three Component Coupling of Aliphatic Alcohols, CO(2), and Alkyl Halides in the Presence of Cs(2)CO(3).Journal of Organic Chemistry.  64:4578-4579. 1999
    1999 Identification of tyrosine sulfation in Conus pennaceus conotoxins alpha-PnIA and alpha-PnIB: further investigation of labile sulfo- and phosphopeptides by electrospray, matrix-assisted laser desorption/ionization (MALDI) and atmospheric pressure MALDI mass spectrometry.Journal of Mass Spectrometry.  34:447-454. 1999
    1999 Cesium promoted O-alkylation of alcohols for the efficient ether synthesisTetrahedron Letters.  40:1843-1846. 1999
    1999 Cs2CO3 promoted O-alkylation of alcohols for the preparation of mixed alkyl carbonatesTetrahedron Letters.  40:1847-1850. 1999
    Sample Preparation in Biological Mass Spectrometry

    Chapter

    Year Title
    2011 Revisiting Jurassic Park: The Isolation of Proteins from Amber Encapsulated Organisms Millions of Years Old.  925-938. 2011

    Teaching Activities

  • Doctoral Thesis Taught course 2019
  • General Biochemistry Taught course 2019
  • Principles of Biochemistry II Taught course 2019
  • Principles of Biochemistry II Taught course 2019
  • Rsrch Exp/MCBS Taught course 2019
  • Persp Biochem/Mole&Cell Bio Taught course 2018
  • Protein Structure & Function Taught course 2018
  • Rsrch Exp/MCBS Taught course 2018
  • Doctoral Research Taught course 2018
  • Doctoral Research Taught course 2018
  • Doctoral Research Taught course 2018
  • Principles of Biochemistry II Taught course 2018
  • Principles of Biochemistry II Taught course 2018
  • Rsrch Exp/MCBS Taught course 2017 - 2018
  • Doctoral Research Taught course 2017
  • Persp Biochem/Mole&Cell Bio Taught course 2017
  • Protein Structure & Function Taught course 2017
  • Rsrch Exp/MCBS Taught course 2017
  • Doctoral Research Taught course 2017
  • Doctoral Research Taught course 2017
  • Principles of Biochemistry II Taught course 2017
  • Principles of Biochemistry II Taught course 2017
  • Rsrch Exp/MCBS Taught course 2017
  • Doctoral Research Taught course 2016
  • Opport/Biochem/Molec/Cell Biol Taught course 2016
  • Doctoral Research Taught course 2016
  • Principles of Biochemistry II Taught course 2016
  • Principles of Biochemistry II Taught course 2016
  • Rsrch Exp/MCBS Taught course 2016
  • Adv Rsrch Exp/MCBS Taught course 2015
  • Doctoral Research Taught course 2015
  • Doctoral Research Taught course 2015
  • General Biochemistry Taught course 2015
  • General Biochemistry Taught course 2015
  • Opport/Biochem/Molec/Cell Biol Taught course 2014
  • Proteomics for Biol Discovery Taught course 2014
  • Doctoral Research Taught course 2014
  • General Biochemistry Taught course 2014
  • General Biochemistry Taught course 2014
  • Education And Training

    Full Name

  • Feixia Chu