Nael Mccarty, Phd

Nael A. McCarty, PhD  Associate Professor  Cystic Fibrosis Scientist, Emory Center for Respiratory Health

Email: [email protected] Research office phone: Arriving in January 2008 Fax: 404-712-9712

Curriculum Vitae

Research Interests:

The primary focus of Dr. McCarty’s work is the molecular physiology of membrane proteins, especially ion channels and receptors that regulate them. Over the past thirteen years as an independent scientist, this work has predominantly centered upon the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is the locus of the primary defect in cystic fibrosis (CF). CFTR is a member of the ABC Transporter superfamily, which forms a Cl--selective ion channel in the membranes of many cell types of epithelial origin; CFTR also serves as the main pathway for transport of glutathione in the airway. The primary research goal of his lab is the development of a functional map of CFTR’s essential domains, to facilitate the design of novel therapies. They apply high-resolution electrophysiological approaches, combined with molecular biological techniques, to achieve this goal. Recent work includes the development of novel assays and reagents for determination of the structure and mechanism of both ion permeation and gating within the channel pore; we have the first evidence for changes in the physical shape of the channel pore associated with gating between open and closed states.

While at Georgia Institute of Technology, Dr. McCarty broadened his perspective beyond CFTR to include work on other ion channels relevant to airway epithelial cells and also on receptors that regulate many physiological processes, including ion channel activity. His lab has isolated a peptide toxin that inhibits CFTR: this is the first peptide toxin targeting a chloride channel of known molecular identity; this is also the first state-dependent inhibitor of CFTR. They also isolated a separate toxin active at the ClC-2 voltage-gated chloride channel, which is also expressed in epithelial cells of the airway. Hence, Dr. McCarty’s lab has pioneered the isolation and use of peptide inhibitors of chloride channels, a major accomplishment during his time at Georgia Tech. Finally, his lab is also interested in understanding G-protein coupled receptors (GPCRs), the targets of the vast majority of pharmaceuticals on the market. GPCRs have recently been shown to heterodimerize in many cell types. However, the functional consequences of heterodimerization are unknown. They are using novel approaches to determine how receptor function differs upon heterodimerization. Importantly, these activities encompass three of the seven research areas of emphasis targeted for growth at Emory: Epithelial Biology, Neuroscience, and Molecular Structure & Interactions. Dr. McCarty is also involved in several other collaborative projects at Georgia Tech and at Emory, as well as with long-term colleagues at the CF Center at UAB.

Ongoing projects in the McCarty lab at Emory include:

Project 1: Probing the dynamic nature of the CFTR chloride channel pore. Project 2: Isolation and characterization of a peptide toxin active at CFTR chloride channels. Project 3: Isolation and characterization of a peptide toxin active at ClC-2 chloride channels. Project 4: Determining the functional consequences of heterodimerization among cardiovascular-relevant G protein-coupled receptors (GPCRs). Project 5: Identification of chemoreceptors involved in chemical defense pathways. Project 6: The role of CFTR in regulating the airway microenvironment.