Positions

Overview

  • I started my research career at Tsinghua University in Dr. Yongbin Yan's and Dr. Haimeng Zhou’s research group as a master student. During my masters degree I used FT-infrared and other spectroscopic methods to study protein unfolding and aggregation of RNAse A. In 2006 I joined the PhD program at the University of North Carolina (Chapel Hill) in the Department of Biochemistry and Biophysics. My work focused on protein dynamics probed by NMR relaxation, under supervision of Dr. Andrew Lee.

    I obtained my PhD in 2011 and began my postdoctoral training in Dr. Traci Hall’s group at National Institute of Environmental Health Sciences. My research focused on structural and functional studies of RNA-binding proteins. This postdoc training not only extended my training to crystallography and RNA biology, but also gave me an opportunity to make use of my expertise in NMR dynamics (acquired during my PhD studies). I joined the UAB Chemistry Department as an Assistant Professor in 2016.

    My lab will build on research projects developed during my postdoctoral training, focusing on the structure and function of intrinsically disordered proteins. Furthermore, the integration of crystallography, NMR, and other spectroscopic methods greatly widens my research scope and enables me characterize both protein structure and dynamics.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2018 Application of tyrosine-tryptophan fluorescence resonance energy transfer in monitoring protein size changes 2018
    2017 U7 snRNP is recruited to histone pre-mRNA in a FLASH-dependent manner by two separate regions of the stem-loop binding protein 2017
    2017 Structural analysis reveals the flexible C-terminus of Nop15 undergoes rearrangement to recognize a pre-ribosomal RNA folding intermediate 2017
    2016 Nop9 is a PUF-like protein that prevents premature cleavage to correctly process pre-18S rRNA 2016
    2016 The molecular basis for ANE syndrome revealed by the large ribosomal subunit processome interactome 2016
    2014 Molecular mechanisms for the regulation of histone mRNA stem-loop-binding protein by phosphorylation 2014
    2013 Supertertiary structure of the MAGUK core from PSD-95 2013
    2011 Phosphorylation of a PDZ domain extension modulates binding affinity and interdomain interactions in postsynaptic density-95 (PSD-95) protein, a membrane-associated guanylate kinase (MAGUK). 2011
    2010 Crystallographic and nuclear magnetic resonance evaluation of the impact of peptide binding to the second PDZ domain of protein tyrosine phosphatase 1E. 2010
    2009 Hidden dynamic allostery in a PDZ domain. 2009
    2008 Hydrophobic core mutations in CI2 globally perturb fast side-chain dynamics similarly without regard to position 2008
    2008 Oligomerization and aggregation of bovine pancreatic ribonuclease A: Backbone hydration probed by infrared band-shift 2008
    2008 Reshaping the folding energy landscape of human carbonic anhydrase II by a single point genetic mutation Pro237His. 2008
    2006 Assisting the reactivation of guanidine hydrochloride-denatured aminoacylase by hydroxypropyl cyclodextrins. 2006
    2006 Oligomerization and aggregation of bovine pancreatic ribonuclease A: characteristic events observed by FTIR spectroscopy. 2006
    2006 Sequential events in ribonuclease A thermal unfolding characterized by two-dimensional infrared correlation spectroscopy. 2006
    2005 Conformational change in the C-terminal domain is responsible for the initiation of creatine kinase thermal aggregation. 2005
    2005 Probing conformational changes of proteins by quantitative second-derivative infrared spectroscopy. 2005

    Research Overview

  • Over 30 percent of the human genome encodes intrinsically disordered protein regions. These disordered regions can co-occur with neighboring folded domains or make up intrinsically disordered proteins alone. Despite being unstructured, intrinsically disordered regions are essential for cell survival and exert regulatory functions by encoding phosphorylation sites. However, the full impact of these regulatory mechanisms on cellular function is still largely unknown. This gap in knowledge is, in part, due to the dynamic nature of these disordered regions that make them difficult to study. Furthermore, dramatic conformational changes, as exemplified frequently by binding-induced protein folding, may also hinder studies seeking to understand the regulatory mechanisms associated with these post-translational modifications.

    My lab seeks to understand the regulation of cellular processes through phosphorylation of intrinsically disordered regions of proteins. Because disordered regions regulated by phosphorylation are abundant in RNA-binding, my lab focuses on two excellent examples in histone mRNA stem-loop binding protein and Serine/Arginine rich splicing factors. Phosphorylation plays vital roles in both of these systems. The goal of our research is to understand how phosphorylation of disordered regions found in these proteins provides functional regulation of this class of proteins at the structural level. In addition, we also seek to determine how defects in phosphorylation of these regions result in cell death or carcinogenesis. Towards these goals, we use an array of biophysical approaches including Nuclear Magnetic Resonance, crystallography and small-angle x-ray scattering. This diverse array of techniques will allow us to characterize both the dynamic and structural aspects of disordered regions. These biophysical observations will then be assessed for their functional consequences using in vivo techniques. The culmination of our research efforts will result in a complete understanding (structural and functional) of how phosphorylation of intrinsically disordered regions of protein regulate cellular processes.

    Keywords - Biochemistry, Regulation of Intrinsically Disordered Proteins, RNA-binding Protein Dynamics and Structure, NMR, Crystallography
  • Education And Training

  • Doctor of Philosophy in Biochemistry and Molecular Biology, University of North Carolina System : Chapel Hill 2011
  • Full Name

  • Jun Zhang