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Our lab is focused on dissecting the cellular and molecular principles underlying a variety of neuron-specific functions and pathologies
iPSC models of Parkinson’s Disease:
Current work focuses on understanding the misregulation of cell-type specific functions in neurodegenerative disorders such as Parkinson’s disease (PD). Using directed differentiation of patient-derived induced pluripotent stem cells (iPSCs), we model complex interactions between dopaminergic neurons, astrocytes and microglia carrying PD-related mutations. By employing cutting-edge microscopy techniques, we study how PD-related mutations affect organelle function and dynamics, as well as overall neuronal physiology. Furthermore, we use sequencing-based approaches to characterize the cell-type specific regulation of gene expression in PD, with the goal of identifying gene regulatory mechanisms that contribute to cellular malfunction in PD.
Dissecting the activity-dependent regulation of synaptic receptors:
We are also interested in how activity-dependent regulation of neurotransmitter receptors modulates synaptic plasticity. We have used CRISPR/Cas9 techniques to tag endogenous receptors in primary cultured neurons. We plan to use single particle tracking and other advanced microscopy techniques to examine the trafficking and recycling properties of endogenous receptors at synapses. Moreover, we will examine how changes in the subunit composition of these receptors also contributes to synaptic plasticity.
Elucidating the molecular principles underlying learning and memory in D. melanogaster:
In addition, we are investigating learning and memory formation in D. melanogaster. Although learning and memory have been extensively studied at the level of neuronal circuits in various organisms, the cellular and molecular events that underlie these processes are still poorly understood. To address this question, we set out to study gene expression dynamics that accompany learning and memory formation in adult flies. By combining fly behavior assays with novel next-generation sequencing based technologies, we are now able to systematically capture gene expression dynamics and regulatory networks in living organisms as they learn and respond to stimulus. Using this approach, we aim to 1) identify novel genes involved in learning and memory formation, and 2) discover novel gene regulatory mechanisms that contribute to memory formation.