A5055357978- Genetics, Aging, and Longevity in Model Organisms
- Neuropeptides and Animal Physiology
- Pharmacological Receptor Mechanisms and Effects
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- Vitamin C and Antioxidants Research
- Glycosylation and Glycoproteins Research
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Nanoparticles: synthesis and applications
- Nuclear Structure and Function
Yale University
2015-2020
Whitney Museum of American Art
2017
University of California, Los Angeles
2014
Allosteric modulators of G protein-coupled receptors (GPCRs) have a number potential advantages compared to agonists or antagonists that bind the orthosteric site receptor. These include for receptor selectivity, maintenance temporal and spatial fidelity signaling in vivo, ceiling effect allosteric cooperativity which may prevent overdose issues, engendering bias by differentially modulating distinct pathways. Here we describe discovery, synthesis, molecular pharmacology δ-opioid...
With the hope of discovering effective analgesics with fewer side effects, attention has recently shifted to allosteric modulators opioid receptors. In past two years, first chemotypes positive or silent (PAMs SAMs, respectively) μ- and δ-opioid receptor types have been reported in literature. During a structure-guided lead optimization campaign μ-PAMs BMS-986121 BMS-986122 as starting compounds, we discovered new chemotype that was confirmed display μ-PAM μ-SAM activity depending on...
The proteasome is an essential regulator of protein homeostasis. In yeast and many mammalian cells, proteasomes strongly concentrate in the nucleus. Sts1 from Saccharomyces cerevisiae linked to nuclear localization. Here, we show that contains a non-canonical bipartite localization signal (NLS) important for both itself proteasome. binds karyopherin-α import receptor (Srp1) stoichiometrically, this requires NLS. NLS viability, over-expressed with inactive interferes 26S import. Sts1-Srp1...