Lu Chen

My research program aims to understand the cellular and molecular mechanisms that underlie synapse function during behavior in the developing and mature brain, and how synapse function is altered in neurodevelopmental disorders. Within this broad research area, I am specifically interested in the following three overall themes.
1. Investigate the synaptic signaling mechanisms regulating homeostatic synaptic plasticity, the role of postsynaptic protein translation in this control, and how these signaling mechanisms are compromised in neurodevelopmental disorders. Toward this goal, we combine molecular, biochemical, electrophysiological, and cell biological approaches to examine retinoic acid signaling pathways that mediate activity-dependent regulation of synaptic function, both globally at a whole cell level or locally with each synapse as an independent computational unit of the neuron. We also explore how genetic mutations implicated in neurodevelopmental disorders alter homeostatic synaptic plasticity in both mouse models and human neurons derived from patient iPS cells.
2. Investigate interactions between retinoic acid-mediated homeostatic synaptic plasticity and other forms of long-lasting synaptic changes (e.g. Hebbian plasticity), how this interaction impacts learning and memory formation at behavioral levels, and how defective homeostatic synaptic plasticity underlies cognitive deficits in neurodevelopmental disorders. Our investigation of molecular mechanisms underlying homeostatic synaptic plasticity provides unique molecular tools with which we could begin to manipulate homeostatic plasticity specifically and examine its impact on Hebbian plasticity. We use both behavioral assays and slice electrophysiology as our functional readouts. Moreover, we developed protocols to investigate memory recall accuracy using activity-dependent genetic labeling in behaving animals, thus further exploring the mechanisms of memory encoding (or lack thereof in the case of disease models) at neural network levels.
3. Investigate synaptic and circuit changes in spinal dorsal horn in peripheral nerve injury-induced neuropathic pain models. We extend our investigations of synaptic plasticity mechanisms from the brain circuits to spinal dorsal horn circuits because we believe some of the most fundamental molecular mechanisms underlying experience-dependent synaptic modifications are shared between similar types of synapses in different regions of the CNS. Indeed, our recent work on synaptic changes driving nerve injury-induced spinal disinhibition supports this notion. The current application builds upon ample preliminary data and applies knowledge generated from our studies in the brain circuits to explore spinal circuits. 
To achieve these goals, we combine expertise spanning molecular and cellular biology, protein biochemistry, stem cell biology, slice electrophysiology, in vivo imaging and MEA recordings, and behavioral assays.