My research is focused on ionotropic neurotransmitter receptors, the receptors responsible for the rapid postsynaptic response in nerve and muscle. These receptors are large oligomeric membrane proteins with subunits surrounding an ion channel that opens when neurotransmitters bind to the receptor. There are two different families of ionotropic neurotransmitter receptors. One family includes nicotinic acetylcholine receptors (AChRs), GABA and glycine receptors, and the other family are glutamate receptors, both NMDA- and AMPA-type glutamate receptors. The overall goal of my research is to understand how nerve and muscle build these receptors and traffic them specifically to and from synapses. These events regulate the number, density and function of the receptors at synapses, which helps define synaptic strength. The same events underlie learning and memory formation, and when they fail, can contribute to a number of diseases including Alzheimer’s disease, Huntington’s Disease, Myasthenia Gravis and Myasthenic Syndromes.
There are several projects ongoing in my lab characterizing the basic cell biology of these receptors, which include receptor assembly, trafficking and clustering. Assembly refers to the processes that transform newly synthesized subunits into functional receptors usually in the endoplasmic reticulum. Trafficking refers to the processes that transport the receptors to and from different location in cells and targets them to these locations. Clustering is the process that packs and maintains the receptors in regions of high density such as synapses. Recently, we have developed new techniques for assaying the protein post-translation modification known as palmitoylation. This work has led to several collaborations in which we are helping to characterize the palmitoylation of a number of different proteins. I also am collaborating with Dr. Paul Selvin (University of Illinois) developing fluorescent single-molecule methods to characterize neurotransmitter receptor subunit composition, stoichiometry and the diffusion/trafficking of these receptors.
Yale University
New Haven, CT
Postdoctoral Fellow - Physiology & Neuroscience
1992
Cornell University Graduate School of Medical Sciences
New York, NY
Ph.D. - Physiology & Biophysics
1986
University College, University of Toronto
Toronto, Canada
B.Sc. - Physics & Zoology
1978
RNA-based translation activators for targeted gene upregulation.
RNA-based translation activators for targeted gene upregulation. Nat Commun. 2023 10 26; 14(1):6827.
PMID: 37884512
Evaluation of an Image-Derived Input Function for Kinetic Modeling of Nicotinic Acetylcholine Receptor-Binding PET Ligands in Mice.
Evaluation of an Image-Derived Input Function for Kinetic Modeling of Nicotinic Acetylcholine Receptor-Binding PET Ligands in Mice. Int J Mol Sci. 2023 Oct 24; 24(21).
PMID: 37958495
Trapping of Nicotinic Acetylcholine Receptor Ligands Assayed by In Vitro Cellular Studies and In Vivo PET Imaging.
Trapping of Nicotinic Acetylcholine Receptor Ligands Assayed by In Vitro Cellular Studies and In Vivo PET Imaging. J Neurosci. 2023 01 04; 43(1):2-13.
PMID: 36028313
Deploying a Single-Energy O-Ring Linac as the Sole Treatment Machine in a Community Setting: A Feasibility Study.
Deploying a Single-Energy O-Ring Linac as the Sole Treatment Machine in a Community Setting: A Feasibility Study. Int J Radiat Oncol Biol Phys. 2021 Nov 01; 111(3S):e514.
PMID: 34701634
Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome.
Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome. Elife. 2021 09 21; 10.
PMID: 34545811
ESCargo: a regulatable fluorescent secretory cargo for diverse model organisms.
ESCargo: a regulatable fluorescent secretory cargo for diverse model organisms. Mol Biol Cell. 2020 12 15; 31(26):2892-2903.
PMID: 33112725
Editorial: Role of Protein Palmitoylation in Synaptic Plasticity and Neuronal Differentiation.
Editorial: Role of Protein Palmitoylation in Synaptic Plasticity and Neuronal Differentiation. Front Synaptic Neurosci. 2020; 12:27.
PMID: 32754027
Development of fluorescence imaging probes for nicotinic acetylcholine a4ß2* receptors.
Development of fluorescence imaging probes for nicotinic acetylcholine a4ß2* receptors. Bioorg Med Chem Lett. 2018 02 01; 28(3):371-377.
PMID: 29277457
Correction: Super-resolution imaging of synaptic and Extra-synaptic AMPA receptors with different-sized fluorescent probes.
Correction: Super-resolution imaging of synaptic and Extra-synaptic AMPA receptors with different-sized fluorescent probes. Elife. 2017 11 08; 6.
PMID: 29116041
Super-resolution imaging of synaptic and Extra-synaptic AMPA receptors with different-sized fluorescent probes.
Super-resolution imaging of synaptic and Extra-synaptic AMPA receptors with different-sized fluorescent probes. Elife. 2017 07 27; 6.
PMID: 28749340