Molecular organization, dynamics, and functions of synaptic supramolecular assemblies at the nanoscale under near-native conditions

I am an assistant professor at Vanderbilt University, where I work in the Department of Cell and Developmental
Biology, the Vanderbilt Brain Institute, and the Center for Structural Biology. My research program focuses on
the molecular organization, dynamics, and functions of synaptic supramolecular assemblies at the nanoscale
under near-native conditions. With a broad background in structural biology and molecular neuroscience, I
have specific training and expertise in synaptic transmission and cellular structure biology, particularly in
cryogenic electron tomography (cryo-ET). My graduate and postdoctoral research has resulted in numerous
high-impact publications. As a postdoctoral fellow, I tackled a thirty-year-old challenge and successfully
revealed the interactions and assembly of the pre-synaptic vesicle fusion machinery for neurotransmitter
release. My work on multi-protein assemblies among the SNARE complex, a small regulatory factor complexin,
and the calcium sensor Syt1 is considered a milestone in the field. I started my independent laboratory at
Vanderbilt University in January 2020. Since arriving at Vanderbilt, I have made great strides in the face of
unprecedented disruption caused by the COVID-19 pandemic, including lab shutdown, limited research
capacity, as well as delay in shipping and installation of key equipment (Titan Krios TEM, FIB-SEM, and cryo-
CLEM). After four years of delving into a new research direction (in situ cryo-ET) at Vanderbilt, I have
established my own unique system and platform for in situ cryo-ET. Taking advantage of this technology and
platform, my laboratory successfully discovered that postsynaptic proteins are organized into subsynaptic basic
unit – we called PSD nanoblocks. These nanoblocks are heterogeneous in size, assembly and distribution,
which likely underlies the dynamic nature of PSD to modulate synaptic strength. This finding provides a more
comprehensive understanding of synaptic ultrastructure and suggests a potential mechanism for PSD
nanoblocks to regulate synaptic strength. Additionally, we collaborated with the Skaar laboratory to reveal the
molecular mechanism of membrane-bound ferrosome organelles containing non-crystalline iron phosphate
biominerals in the human pathogen Clostridioides difficile using cryo-ET. We also made significant strides in
the development of novel labeling techniques for 3D cryo-electron microscopy.