Cellular mechanisms of neuronal dysfunction

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

Abstract

We identified a novel phenomenon in cell biology by which decreases in endoplasmic reticulum calcium levels leads to the secretion of resident proteins of the ER lumen. We also show that the cell upregulates KDEL receptor expression to attenuate the loss of these proteins. We coined the term Exodosis to refer to the loss of ER resident proteins in response to ER calcium depletion. This work is published in Cell Reports. We found several neuronal activators (methamphetamine, glutamate, DREADDs) that can positively regulate the CMV promoter which is commonly used in viral vectors for neuroscience studies and gene therapy applications in humans. This work is published in Molecular Therapy Methods in Clinical Develpment. We developed a novel set of transgenic tools for performing cell-specific genome editing in the adult rat brain. This work is published in Neuron. Using C elegans as a model, we examined the worm ortholog to human MANF and discovered that MANF acts as a negative regulator of an ER stress response and innate immune response in worms. The work is published in the European Journal of Cell Biology. In collaboration with Lorenzo Leggio (NIAAA/NIDA), we developed a ghrelin receptor knockout rat to aid in the understanding of ghrelin signaling and substance abuse. This work is published in the International Journal of Obesity