Dr. Free received his B.S. from Capital University in Biology and Chemistry and his Ph.D. from The Ohio State University in Pharmacology, where he studied the characterization and regulation of neuronal nicotinic receptors with Dr. Dennis McKay.
Dr. Free came to the NIH for a postdoctoral fellowship in the Molecular Neuropharmacology Section with Dr. David Sibley to investigate the regulation and proteomics dopamine receptor trafficking and was appointed as a research fellow in 2009. Dr. Free was appointed as an NINDS staff scientist in 2011 and his work focuses on the identification and optimization of dopamine receptor chemical probes and therapeutics, and the use of those compounds both as clinical candidates and probes to study molecular interactions and signaling of dopamine receptors.
In April, 2022, Dr. Free joined the NINDS Office of the Scientific Director (OSD) as Assistant Director of Science Operations Support. In this capacity, Dr. Free:
- Oversees policy, planning, and operations of NINDS and shared/collaborative core facilities
- Serves as an ex-Officio member for key NINDS advisory committees.
- Supports operational and strategic space planning and tracking, physical emergency management and facilities activities, and lab renovations/shutdown planning.
- Interfaces with data storage facilities and IT operations.
- Oversees the equipment reallocation processes, equipment calls, research collaboration calls/awards.
- Serves as internal resource/liaison for employees, trainees and CIVIL, functioning as an internal resource to explain options and facilitate support.
- Provides scientific leadership of the Personnel Transition Unit (PTU), a program designed to reassign well performing federal employees deemed displaced due to departure/retirement of a PI or restructuring (i.e., lab closure, consolidation, downsizing, etc.).
The Molecular Neuropharmacology Section is focused on the identification and optimization of dopamine receptor chemical probes and therapeutics, and the use of those compounds to study molecular interactions and signaling of dopamine receptors. We have been successful in identifying a number of different unique compounds with pharmacological characteristics not previously identified. My primary interests fall under two broad categories: dopamine receptor compounds that elicit functionally selective actions; meaning that they stimulate, or inhibit, one signaling pathway, but not others, and the subsequent underpinnings of how this functional selectivity works; and secondly, the identification of compounds that show exceptional receptor subtype selectivity, meaning that they act on one dopamine receptor subtype without affecting other subtypes.
To this end we are currently engaged in several primary projects including 1) Discovery and characterization of a G-protein signaling-biased agonist of the D2 dopamine receptor which has led to an understanding of the allosteric control of GPCR biased signaling via a micro-switch in the extracellular ligand binding site. Further we are examining the importance of GRK2 in mediating this bias signaling. 2) Discovery, optimization, and development of receptor subtype-selective antagonists, partial agonists, agonists, and positive allosteric modulators of the dopamine receptors as therapeutic leads. A number of compounds are being pushed through lead compound optimization and development studies. 3) Investigations into the mechanisms of D2R dopamine receptor inhibition by anti-cancer imipridone compounds.