Zezong Gu, MD, PhD
Degrees: PhD, Cell Biology and Neuroscience, University of Texas Medical Branch (UTMB) at Galveston, TX; MD, Tianjin Medical University, Tianjin, China
Additional study: Postdoctoral Associate, Postdoctoral Fellow, Burnham Institute for Medical Research, La Jolla, CA
Academic appointments: Assistant Professor of neuroanatomy and neuroscience; Adjunct Assistant Professor, Burnham Institute for Medical Research, La Jolla, CA
Research description: Research interests in Gu Laboratory focus on understanding the molecular mechanisms of redox modulation, particularly the roles of nitrosative and/or oxidative stress in cell signal transduction machinery and the impact to neurological diseases. Reactive nitrogen/oxygen species (RNS/ROS) play diverse roles in regulating biological processes ranging from development to disease. Dr. Gu and his colleagues discovered that RNS/ROS-induced nitrosative and oxidative stress alters functions of both extracellular and intracellular key molecules in neurodegenerative disorders, including matrix metalloproteinases for their aberrant proteolytic activity to neuronal cell death in stroke and retinal neurodegeneration, and parkin, a ubiquitin E3 ligase linked to misfolded protein aggregates in the sporadic form of Parkinson’s disease.
Current research activities in the laboratory involves (1) therapeutic potential of mechanism-based inhibition of matrix metalloproteinases in stroke and retinal neurodegeneration; (2) molecular imaging of proteolysis in cells and in animals in vivo; (3) mass spectrometry (MS)-based analysis of sub-proteome for cysteine thiol posttranslational modifications (PTM) and molecular modeling for PTM-induced conformational changes; and (4) the molecular mechanisms of redox modulation of proteins and their down-stream signal transduction pathways that lead to dysfunctional ubiquitination, aggregation of misfolded proteins, aberrant proteolysis and neuronal cell death in neurodegenerative disorders. Ultimately, the findings may lead to identify potential therapeutic targets to intervene aberrant proteolysis, dysfunctional protein degradation, and neuron injury and death in neurodegenerative disorders.
Gu Laboratory has established and/or adopted various model systems, such as cell-free protein interaction, cell lines and/or primary neuronal cultures, and in vivo animal models representative of cerebral ischemic stroke, Parkinson’s and Alzheimer’s disease, and retinal degeneration. Multi-disciplinary approaches used in the laboratory include microsurgery, pharmacology, in vivo genetics, protein biochemistry, molecular and cell biology, immunocytochemistry, confocal/deconvolution microscopy with capacity for 3D and time-lapse imaging, molecular structure modeling, and comprehensive mass spectrometry strategies. These experimental approaches allow us to conduct translational research and investigate the mechanisms underlying protein aggregation and degradation, aberrant proteolysis, as well as neuronal cell injury nad death by environmental risk factors like oxidative/nitrosative stress.