The primary products of the genome are large number of expressed proteins dubbed the proteome, which codifies molecular organization in cells and is a major domain of ongoing scientific inquiry. Our research centers on identifying and characterizing proteome interaction networks for the dopamine and nicotinic acetylcholine receptors in order to better understand the function and regulation of these receptor systems in various types of cells. Recent projects include:
Delineating the role of the nicotinic acetylcholine receptor in synaptic growth and nerve regeneration
Cholinergic neurotransmission plays an important role in brain and spinal cord development shaping synaptic plasticity and guiding regeneration. Various nicotinic receptors (nAChRs) are expressed early in the human brain and spinal cord participating in signals that shape neural connectivity and synaptic wiring. We are interested in the mechanism by which the α7 nACh regulates synaptogensis through its early expression in embryonic neurons of the cortex and hippocampus. This receptor appears genetically linked to various developmental brain disorders including schizophrenia. We have shown a role for α7-mediated calcium and G protein signaling in the regulation of cytoskeletal motility leading to neurite retraction at the growth cone. Outstanding questions remain on the role of the α7 receptor in shaping synaptogensis in the developing brain.
Spatio-temporal calcium signal for cytoskeletal growth
Calcium serves as dynamic regulator of biological signaling events within cells owing to its ability to differentially activate various secondary messenger and effector pathways. Spatial and temporal cytosolic calcium level fluctuations are known to encode information for signaling and cytoskeletal motility. However, it is unclear how calcium transients encode information for processes such as cytoskeletal remodeling during growth and migration. Using real-time calcium and cytoskeletal imaging we are examining interactions between these systems in the growth. In particular, we aim to explore how α7 nACh regulates cytoskeletal growth through calcium entry and store release in caclium microdomains where the receptor is expressed.
Identification and characterization of receptor interactomes
A long standing interest has been the delineation of receptor interactomes that underlie receptor signaling and function. While a number of approaches have been optimized for the isolation, purification, and proteomic characterization of receptor–protein interaction networks (interactomes) in cells, the capture of receptor interactomes and their dynamic properties in vivo remains a challenge. We are developing tools aimed at examining interactions of the nAChR from neural, neuroendocrine, as well as immune cells. An understanding of nAChR interactomes spearheads molecular biology by enabling the generation of new hypotheses and can lend insight into improving drug development .