Purpose
The Harraz lab aims to elucidate the interplay between protein homeostasis and signal transduction to leverage for drug discovery in neuroscience.
Our research interrogates a novel selective autophagy pathway of membrane proteins and its effects on reward behavior and neurodegeneration.
Cells sense and react to their environment by changing the composition of plasma membrane proteins. Cell surface remodeling is essential for regulating the cells' interaction with the extracellular milieu. Learning how membrane-proteins are identified and eliminated is crucial for understanding cell and organismal homeostasis.
Our work uncovers a novel high-affinity receptor for cocaine and explores the role of autophagic proteostasis in substance use disorder.
We found that sub-nanomolar levels of cocaine induce autophagy in neurons. This effect on autophagy is three orders of magnitude more potent than cocaine-mediated inhibition of the dopamine transporter (DAT) activity. Our research shows that autophagic degradation of DAT primarily mediates the stimulant effect of cocaine (link to the paper). Using CRISPR/Cas9 generated mutant mice, we are interrogating the role of autophagy in the selective targeting of membrane proteins to regulate cell signaling, modulate behavior, and mediate neurotoxicity.
We identified the brain acid-soluble protein-1 (BASP1) as a novel high-affinity receptor for cocaine (Kd 7 nM) (link to the paper). Using BASP1 conditional knockout mice, the Harraz lab currently characterize BASP1 as a candidate receptor for cocaine.
Department of Psychiatry
University of Maryland School of Medicine
685 W Baltimore Street MSTF 934D
Baltimore, MD 21201
Contact Us
Email: mharraz@som.umaryland.edu
Office: (410) 706-3023
