The Yocum Lab is interested in understanding the role that “peripheral” GABAA receptors play in immune and lung physiology. Though best known for its role in central nervous system inhibitory neurotransmission (hence its importance in anesthetic pharmacology), the GABAA receptor is expressed in several non-neuronal cell types, including multiple immune cell subtypes and airway smooth muscle. the Lab demonstrated that manipulation of this receptor’s activity has functional consequences at the level of the immune cell and whole organism in a murine lung inflammation model. The lab is seeking to manipulate these effects for therapeutic advantage. This work is done in collaboration with medicinal chemists at the University of Wisconsin-Milwaukee, who have designed subunit-selective GABAA receptor modulators that do not cross the blood-brain barrier after systemic administration, eliminating the potential for sedative side effects.
In particular, the lab is interested in the effects that GABAA receptor activation has on immune cell calcium signaling. Utilizing a unique and powerful tool known as precision-cut lung slice calcium imaging, the Yocum laboratory is able to image the calcium dynamics of immune cells in situ in “living” lung tissue using a custom-designed confocal microscope. This allows the research team to maintain much of the complex environment of in vivo immune cell activation while simultaneous examining the effects of GABAA receptor modulation on immune cell calcium oscillations, a key determinant of cellular activation and function. These studies are done in collaboration with Dr. Jose Perez-Zoghbi, also a member of the Department of Anesthesiology. This work has been funded by the Foundation for Anesthesia Education and Research (FAER), the Stony Wold-Herbert Fund, and the National Institutes of Health.