|Title||Assistant Professor with Secondary Appointment in Neuroscience|
Cells are composed of around 70% water with a plasma membrane also permeable to water. So keeping cell volume constant in response to osmotic challenges is fundamental to life. This is achieved in mammals by maintaining a stable blood plasma osmolarity (near 300 mOsm/L) and by possessing a variety of mechanisms that allow individual cells to monitor and recover their volume following osmotic swelling or shrinkage. Defective osmoregulation leads to various human disorders, including dehydration, hypertension, renal and neurological diseases. However, the identity of many key osmosensing molecules has been a long-standing mystery. Our goal is to elucidate the molecular mechanisms of mammalian osmotic regulation at both the cellular and whole body levels. To this end, we combine several techniques including high-throughput functional genomics, electrophysiology, mouse genetics, imaging, and biochemistry. For example, we recently performed a genome-wide RNAi screen and co-discovered SWELL1 (LRRC8A) as an essential component of the elusive Volume-Regulated Anion Channel (VRAC). VRAC is required for maintaining cell volume in response to osmotic swelling. Future studies can now address the function and regulation of the ubiquitously expressed VRAC channel in normal and disease states.