Rosenbaum Lab
Principal Investigator: Daniel Rosenbaum
Institution: The University of Texas Southwestern Medical Center (Dallas, TX)
Primary Subfield: Neuroscience
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
Project Summary/Abstract The goal of this project is to use atomic structures of the activated human D2 dopamine receptor (DRD2) to develop potent small molecule positive allosteric modulators (PAMs) of this G protein-coupled receptor (GPCR) as biological tools and future therapeutic lead compounds. Dopamine activation of DRD2 regulates movement, reward and cognition among other physiological functions, and attenuation of dopamine signaling through this receptor is an important contributor to Parkinson’s disease (PD) which affects approximately 10 million people worldwide. Current therapeutics targeting DRD2 include orthosteric agonists that mimic dopamine for PD, however dopamine replacement therapy is unable to fully restore the natural spatiotemporal patterns of dopamine signaling in the brain, leading to loss of efficacy over time and other side effects. A complementary approach to targeting the orthosteric pocket of DRD2 is using a positive allosteric modulator (PAM) to act synergistically with endogenous dopamine to restore physiologically appropriate dopamine signaling. Despite the central importance of DRD2 signaling and the potential therapeutic benefits of positive allost…
Active NIH Awards
- 1R01NS143214-01A1: Structure-guided discovery of positive allosteric modulators for the D2 dopamine receptor (2026)
- 5R35GM136387-07: Structural mechanisms of Scap/SREBP signaling in membrane homeostasis (2026)
- 2R35GM136387-06: Structural mechanisms of Scap/SREBP signaling in membrane homeostasis (2025)
- 5R35GM136387-05: Membrane signaling protein modulation by lipids and drugs (2024)
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