Microfluidic device to monitor cellular proteostasis in rodent serum

In collaboration with Dr. Nicole Morgan (NIBIB), we are developing a device to monitor changes in cellular proteostasis as a consequence of exposure to blood constituents. Our initial work is to demonstrate feasibility of growing reporter cell lines in rodent serum and testing responses to chemical induction of altered proteostasis.   Students working on the project will be exposed to microfluids, cell culture, bioluminescent reporters and various biochemical assays.

Our research group, the Cellular Stress and Inflammation (CSI) Section at the National Institute on Drug Abuse (NIDA) Intramural Research Program (IRP), studies how substances of abuse cause cellular dysfunction. Towards this goal, we use molecular, cellular, pharmacological, transgenic and bioinformatic approaches to investigate the disruption of endoplasmic reticulum (ER) homeostasis in the context of substance use disorder and neurodegeneration. By examining mechanisms of cellular dysfunction, we seek to identify gene- and drug-based therapies for human disease. Our primary focus is understanding the contributions of ER stress and ER calcium dysregulation to neuronal dysfunction caused by exposure to addictive substances and neurodegenerative diseases. Specifically, our lab discovered that ER resident proteins are secreted into the extracellular space following depletion of ER calcium in a process we termed “exodosis.” This redistribution of ER resident proteins causes neuronal dysfunction and contributes to neuroinflammation and cell death.  We are actively studying exodosis as a therapeutic target and readout of human disease states.