Research Projects

RESEARCH PROJECTS

Roles of trophic factors on synapse formation

The simple model system of the Lymnaea brain provides a unique opportunity for investigating molecules or cellular events at a resolution of single neurons (e.g. single cell qPCR). Electrophysiological measurement and quantities of synapses between single pre- and post-synaptic neurons (soma-soma synapses) can be easily achieved using intracellular recording techniques. This model, along with other modern neuroscience techniques such as calcium imaging, immunocytochemistry, confocal microscopy, and molecular techniques, will allows us to investigate 1) how trophic factors (e.g. NGF, BDNF, EGF etc) regulate the development of synaptic specificity patterns (electrical versus chemical, excitatory versus inhibitory, cholinergic versus dopaminergic etc), 2) the precise acting sites of trophic factors (presynaptic versus postsynaptic), and 3) their molecular targets and cellular pathways (genes, proteins, organelles, or signaling cascades etc)

Intrinsic and extrinsic factors that regulate neurite outgrowth and regeneration

The lab specifically focuses on 1) the neuronal regenerative capability in young and aged animals, (2) the roles of cytoskeletal components (e.g. microtubules, microfilaments, neurofilaments), and (3) the genetic and environmental factors that affect dynamic processes of cytoskeletal assembly, disassembly, and stabilization during neuronal outgrowth and regeneration. The objective is to identify intrinsic and/or extrinsic factors that are important for neurite outgrowth and regeneration.

Environmental stressors on animal development and behaviors

Biochemical or neuronal mechanisms of feeding, respiratory, reproductive, learning and memory behaviors are also explored in the laboratory using Lymnaea stagnalis. These include the impact of changes in pH, temperature, oxygen levels, toxins, predators etc. in both embryonic development and adult animal behaviors.

 

Environmental factors and large neuronal network assembly and function in cultured rat neurons

The lab explores the neuronal and synaptic influence of a variety of environmental factors in the central nervous system. These include clinical medicines, recreational drugs and environmental pollutants on brain development and function. Specifically, we will study how environment factors impact rat cortical or hippocampal 1) cell viability, 2) neurite outgrowth, 3) cytoskeletal components (Tutulin, F-actin), 4) mitochondrial integrity and function, 5) synaptic proteins, and 6) circuitry development etc.

Effects of hyperglycemia on neuronal metabolism and autophagy in murine cortex

Hyperglycemia, or elevated blood glucose, is a major characteristic of type II diabetes, a condition that affects over 300 million people worldwide. Hyperglycemia specifically has been shown to contribute to the development of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Common to these conditions is impaired regulation of autophagy, a cellular self-degradation process that clears out excess protein aggregates and damaged organelles like mitochondria. Our lab has found evidence indicating that the neurotrophic factor progranulin may help alleviate neurodegeneration due to hyperglycemia, but the pathway(s) that it works through are unknown.

This project is exploring the role of two kinases (proteins involved in phosphorylation): ERK1/2 and GSK3β in progranulin's mechanism of action. We are investigating this in cell cultures (in vitro) and tissue samples (ex vivo) of mice that will be treated with high glucose and progranulin. Our experiments include western blotting, immunofluorescence imaging, electrophyiological testing, and microplate assays to measure neuronal autophagy, metabolism, function, and health.