Frank Park, PhD
*CV in .pdf
Research:
The Park lab is focused on elucidating the basic mechanisms involved in epithelial cell repair/expansion in distinct mouse and rat models of kidney disease in the hopes of identifying new therapeutic interventions for these diseases. Renal epithelial cells are constantly challenged with biological insults, such as chemical toxicity or ischemic injury. Depending on the severity of the injury, epithelial cells are capable of initiating and progressing through a highly organized repair process in which epithelial cell undergo partial de-differentiation, cell migration and proliferation to re-form functional nephrons. In the context of genetic mutations like those observed in polycystic kidney disease (PKD), the cystic epithelial cells are considered to be in a state of “futile” repair. The cystic gene mutations associated with this disease are believed to activate repair processes in such a manner that the initiating signal cannot be “turned off” leading to epithelial cell expansion, cyst formation and abnormal tissue architecture.
At this time, the goal of our lab is to identify factors that are involved in the process of normal epithelial cell repair. It is our belief that these factors that modulate repair mechanisms in the renal epithelial cell may be inappropriately expressed or functioning in a model of irresponsible repair, which will be PKD in our studies. Currently, we are focusing on a group of receptor-independent regulators of G-protein signaling known as Activator of G-protein signaling (AGS) in distinct models of renal injury and/or damage.
G-protein signaling modulators. G-protein mediated signal transduction is a highly regulated and complex process. It was long believed that G-protein subunit activation/inactivation was exclusively controlled by cell surface or G-protein coupled receptors (GPCRs). In the past 15 years, however, there are emerging new discoveries that G-protein activity can be regulated through non-receptor mediated mechanisms. One such group of receptor-independent G-protein regulators is AGS proteins as described above. In recent studies from our lab, we have focused on one of the AGS protein, specifically G-protein signaling modulator 1 (GPSM1) also known as Activator of G-protein signaling 3 (AGS3), as a critical regulator of epithelial cell repair. Our lab has demonstrated elevated protein expression of GPSM1/AGS3 in murine kidney lysates following acute kidney injury (Regner et al., FASEB J., 2011) or from kidneys with genetic mutations associated with ARPKD or ADPKD (Nadella et al., JASN, 2010). Functionally, genetic loss of GPSM1/AGS3 resulted in significant impairment of renal epithelial cell recovery following bilateral ischemia-reperfusion injury (IRI) (Regner et al., FASEB J., 2011). We are currently exploring the role of a genetic knock-out of Gpsm1 in mice models of ADPKD to determine its effects on cystogenesis.
It is our hypothesis that GPSM1 acts as a protein that modulates epithelial cell repair. In the absence of any genetic defects, renal epithelial cells are capable of full recovery following injury, which appears to be partly attributed to the induction of GPSM1. In pathological situations in which genetic mutations promote incomplete repair, i.e., ADPKD, abnormally high GPSM1 expression cannot overcome the loss of other primary gene products leading to “futile” repair by the cystic epithelial cell.
Degrees:
BS - McGill University, Montreal, QC, 1989-1993
PhD - Medical College of Wisconsin, Milwaukee, WI 1993-1998
Postdoctoral:
Stanford University, Stanford, CA, 1998-2001