Molecular and Cellular Mechanisms underlying
Brain Development and Degeneration
Axon development and brain wiring. Directed cell motility is fundamental for many developmental events including neural development,
and it underlies many pathological events such as cancer-cell metastasis. We investigate directed cell motility in nerve cells, aiming to understand how developing axons
extend and navigate to reach their specific target cells to form synaptic connections. We focus on the spatiotemporal signaling and cytoskeletal events that enable the motile tip
of developing axons, the growth cone, to respond to environmental cues to reach their specific targets.
- Li et al (2022): Signal amplification in growth cone gradient sensing by a double negative feed backloop among PTEN, PI(3,4,5)3, and actomyosin. Mol Cell Neurosci. DOI:10.1016/j.mcn.2022.103772.
- Pollitt et al (2020): LIM and SH3 protein 1 localizes to the leading edge of protruding lamellipodia and regulates axon development. Mol Biol Cell. DOI:10.1091/mbc.E20-06-0366.
- Lee et al (2013): Dynamic localization of G-actin during membrane protrusion in neuronal motility. Curr Biol. DOI:10.1016/j.cub.2013.04.057.
Synapse formation and plasticity. Synapses represent the basic unit of neuronal communications and are composed of paired pre- and post-synaptic terminals.
Synapses are plastic and undergo short- and long-term modifications during development, as well as during learning and memory. We investigate the cytoskeletal regulation of
synaptic structure, function, modification, and disruption.
- Myers et al (2022): Actin capping protein regulates postsynaptic spine development through CPI-motif interactions. Front Mol Neurosci. DOI: 10.3389/fnmol.2022.1020949.
- Omotade et al (2018): Tropomodulin Isoform-Specific Regulation of Dendrite Development and Synapse Formation. J Neurosci. DOI: 10.1523/JNEUROSCI.3325-17.2018.
- Lei et al (2017): Phosphoinositide-dependent enrichment of actin monomers in dendritic spines regulates synapse development and plasticity. J Cell Biol. DOI: 10.1083/jcb.201612042.
Brain injury and neurodegeneration. Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson disease (PD), Huntington’s disease (HD),
and Frontotemporal lobar dementia (FTD), involve progressive disruption of brain function and subsequent neuronal loss that are more prevalent in aged populations. Physical insults
to the head, even those mild ones, can set in motion latent pathologic processes that later emerge to cause neurodegenerative conditions. We use a novel Drosophila
mild head injury model to investigate how early exposure to mild head trauma can lead to long-term deficits and brain degeneration. This research program employes innovative approaches,
inclding AI-empowered quantitative analyses, to interogate the mechanisms underlying the sex difference and age dependence in neurodegeneration.
- Behnke et al (2021): Repetitive Mild Head Trauma Induces Activity Mediated Lifelong Brain Deficits in a Novel Drosophila Model. Scientific Reports. DOI: 10.1038/s41598-021-89121-7.
- Behnke et al (2021): A protocol to detect neurodegeneration in Drosophila melanogaster whole-brain mounts using advanced microscopy. STAR protocols. DOI: 10.1038/s41598-021-89121-7.