I am a biochemical neuropharmacologist, whose expertise is on cannabinoid receptor signal transduction. I am noted for my discovery of the CB1 receptor for cannabinoid agonists, development of the radioligand binding assay for the cannabinoid receptors that led to their identification, and development of antibodies that have been made available to researchers world-wide. I have worked with academic and private sector chemists in characterization of the structure-activity relationships of cannabinoid receptor agonists and my investigation of ligand-biased G protein activation has received editorial commentary.
The Howlett Lab investigates signaling via cyclic AMP, inositol triphosphate, Ca2+, NO, cGMP, and kinases using rodent brain and cultured cell models, biochemical and histochemical methods, pharmacological probes, and stable over-expression and knock-down of proteins. Recent studies are directed at our understanding of protein interactions that modulate the CB1 receptor by allosteric interaction, particularly targeting G protein isoforms, ß-arrestins and CRIP1a (cannabinoid receptor interacting protein 1a). My lab has developed antibodies that select for various sites on the protein that can identify functional domains, and over-expression and siRNA knock-down strategies for elucidated the regulatory mechanisms. As a result, we now know that CRIP1a alters CB1 preference for Gi/o subtypes, promoting the association with Gi1 and Gi2, but reducing the association with Gi3 and Go. In addition, CRIP1a and ß-arrestin compete for binding to sites involved in internalization evoked by cannabinoid agonists as well as cellular signaling pathways. Students working on this project will move the field forward in our understanding of cannabinoid receptor regulation of neuronal properties, which is particularly important as this selectivity is critical to emerging new cannabinoid medicines.
Educational Program Involvement
Integrative Physiology and Pharmacology PhD
Program Research Interest: Drug and Alcohol Abuse, Cardiovascular Physiology and Hypertension, Regenerative Medicine, Neuro- and Behavioral Pharmacology, Cancer Therapeutics Endocrinology, Diabetes, and Metabolism Lifespan Physiology.
Graduate Programs in Neuroscience
Program Research Interest: Addiction and Substance Abuse, Behavioral and Systems Neurobiology, Development and Plasticity, Molecular Neurobiology, Neurological Disease and Aging, Neuropharmacology, Sensory Neurobiology
Molecular Medicine and Translational Science PhD
Program Research Interest: Analytical approaches to molecular and cellular synthesis, structure and function, Genetics and gene regulation, Cell communications, Organ systems, Pathophysiology