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 brain and immune cells. Ongoing 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 through the regulation of synaptic plasticity and regeneration. Various nicotinic receptors (nAChRs) are expressed early in the human nervous system and signal to 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 function is important because studies suggest that genetic modification to the α7 nACh can contribute to important developmental brain disorders including schizophrenia and autism. Our work reveals that α7-mediated calcium and G protein signaling is in important in neural development through an ability to directly regulate cytoskeleton at the growth cone. Outstanding questions remain on the role of the α7 receptor in shaping synapse formation in specific regions of the developing brain.
Spatial and temporal aspects of calcium signaling during growth
Calcium serves as dynamic regulator of biological signaling events within cells owing to its ability to differentially activate various secondary messenger pathways. Spatial and temporal cytosolic calcium level fluctuations encode information that drives cytoskeletal motility. It is still unclear however how such information in conveyed by the nature of the calcium transient signal. Using real-time calcium and cytoskeletal imaging in growing neural cells we are examining interactions between cytosolic calcium and actin and tubulin growth. In particular, we explore how the calcium activating properties of the α7 nACh regulates cytoskeletal growth through calcium entry and store release in calcium microdomains.
Identification and characterization of receptor interactomes
A long standing interest has been the delineation of receptor interactomes that underlie receptor signaling, function, and can enable the generation of new hypotheses for drug development .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 experimental and computational tools aimed at the study of receptor interactomes in neural, endocrine, and immune cells.