Daniel B. Williams, Ph.D.
The focus of Dr. Wiliams' laboratory is on the role of hormones and other modulators in the CNS, focusing on the GABAA receptor. The GABAA receptor is part of the main inhibitory system in the CNS; modulation of the GABAA receptor could have effects in many behaviors and disorders including epilepsy, sleep, stress, and reward, including food intake and drug abuse. Emphasis is currently on a simultaneous inhibitory effect of insulin on GABAA receptors; an effect that could be especially important in food intake; and in the pancreas, in the control of glucagon secretion. We are looking at the subunit dependence of this insulin effect, and will investigate if related peptides such as glucagon and the IGF's have similar effects. Laboratory studies also include GABA-active steroids such as certain metabolites of progesterone and cortisol; we have found a mutation in a GABAA subunit that causes extreme sensitivity of the receptor for steroids. We will investigate if this residue could be one of the steroid binding sites, and if similar mutations in other subunits cause similar effects. Finally we will look at piperidine modulation of the GABAA receptor and whether modulation by piperidines could play a role in those ligands potential ability to treat cocaine addiction.