My focus is on the basic molecular mechanisms involved in neuronal signaling. Specifically I study the pentameric ligand-gated ion channel (pLGIC) family of receptors and the relationship between their structure and function. My current projects revolve around the nicotinic acetylcholine receptor (nAChR) subfamily with specific focus on the alpha5 accessory subunit.
I completed my doctoral thesis at the University of California-San Diego under the supervision of Dr. Palmer Taylor who at the time was the dean of the school of Pharmacy. Although I obtained my degree through the department of Biochemistry and Chemistry with the co-supervision of Dr. Elizabeth Komives, my training spanned the themes of pharmacology, neuroscience, and biochemistry. In an effort to study the specificities of ligand binding and subsequent therapeutic development against neuro-degenerative diseases, I created a humanized template of the alpha7-nAChR extracellular domain during my doctoral work. This X-ray crystallographically resolved template was used in an in situ click-chemistry approach to fragment based drug design against the alpha7-nAChR receptor. Additionally in conjunction with Dr. John Yamauchi we adapted a previously developed G-protein muscarinic acetylcholine receptor cell-based neurotransmitter fluorescent engineered reporter (CNiFER) to the pLGIC family.
In my post-doctoral fellowship with Dr. Pierre-Jean Corringer in the department of Neuroscience my focus shifted to primarily a structural biological approach. I worked with glycine receptors, nAChRs, and prokaryotic pLGICs to study the mechanisms of activation. My specific works included: using an electrophysiological approach I studied the mechanism of proton-activation of the Gloeobacter violaceus ligand-gated ion channel (GLIC), studying lipid binding to the GLIC and a GLIC/glycine receptor chimera, and attempting to incorporate a glycine binding site in the GLIC. In collaboration with Dr. Pierre Lafaye and the laboratories of Pierre Fabre we created VHH nanobodies against specific nAChR extracellular domain sites. Finally in collaboration with Dr. Marc Delarue, I functionally described a new proteobacterial pLGIC found in an endosymbiont of Tevnia jerichonana, termed sTeLIC, which was structurally resolved by Dr. Haidai Hu.