Gelatin maleimide microgels for hematopoietic progenitor cell encapsulation.

Hematopoietic stem cells (HSCs) are the apical cells of the hematopoietic system, giving rise to cells of the blood and lymph lineages. HSCs reside primarily within bone marrow niches that contain matrix and cell-derived signals that help inform stem cell fate. Aspects of the bone marrow microenvironment have been captured in vitro by encapsulating cells within hydrogel matrices that mimic native mechanical and biochemical properties.

CB allosteric modulators and their therapeutic potential in CNS disorders.

CB is the most abundant GPCR found in the mammalian brain. It has garnered considerable attention as a potential therapeutic drug target. CB is involved in a wide range of physiological and psychiatric processes and has the potential to be targeted in a wide range of disease states.

A novel allosteric modulator of the cannabinoid CB receptor ameliorates hyperdopaminergia endophenotypes in rodent models.

The endocannabinoid system (eCBs) encompasses the endocannabinoids, their synthetic and degradative enzymes, and cannabinoid (CB) receptors. The eCBs mediates inhibition of neurotransmitter release and acts as a major homeostatic system. Many aspects of the eCBs are altered in a number of psychiatric disorders including schizophrenia, which is characterized by dysregulation of dopaminergic signaling.

Behavioral Effects of a Potential Novel TAAR1 Antagonist.

The trace amine associated receptor 1 (TAAR1) is a G-protein coupled receptor expressed in the monoaminergic regions of the brain, and represents a potential novel therapeutic target for the treatment of neurological disorders. While selective agonists for TAAR1 have been successfully identified, only one high affinity TAAR1 antagonist has been described thus far. We previously identified four potential low potency TAAR1 antagonists through an screen on a TAAR1 homology model.

Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells.

A number of pathological conditions have been linked to mutations in the dopamine transporter gene, including hereditary dopamine transporter deficiency syndrome (DTDS). DTDS is a rare condition that is caused by autosomal recessive loss-of-function mutations in the dopamine transporter (DAT), which often affects transporter trafficking and folding. We examined the possibility of using pharmacological chaperones of DAT to rescue DTDS mutations.

In-vivo pharmacology of Trace-Amine Associated Receptor 1.

Trace-amines (TAs) are endogenous amines that are implicated in several physiological processes including modulation of aminergic neurotransmission. These compounds exert their effect by activating a class of G protein-coupled receptors termed Trace-Amine Associated Receptors (TAARs), where TAAR1 is the only human receptor that has been shown to bind endogenous TAs. Most of the studies have focused on studying the role of TAAR1 on modulation of the dopamine transmission.

A β-lactamase based assay to measure surface expression of membrane proteins.

Measurement of cell surface expression is an essential part of studying membrane proteins. Traditional techniques for measuring surface expression depend on the availability of appropriate radioligands or antibodies towards extracellular epitopes of a protein of interest. The current protocol outlines the use of an assay to monitor surface expression of membrane proteins tagged with a bacterial β-lactamase in mammalian cell lines.

A novel assay for measurement of membrane-protein surface expression using a β-lactamase.

The trafficking of membrane proteins is dynamic and contributes to the homeostatic control of their cell surface localization and their function in signal transduction. Therefore, it is important to have sensitive techniques that allow measurement of surface expression. The current assays for such measurement are time consuming and low throughput.

Measurement of G protein-coupled receptor surface expression.

The quantity of G protein-coupled receptors (GPCRs) expressed on the cell surface is an important factor regulating receptor signaling. Maturation, internalization, recycling and degradation together determine the net amount of receptor surface expression. Understanding every aspect of the receptor lifecycle will facilitate the development of therapeutic applications.