GSBS Student Awarded American Heart Association Grant
GSBS student, Justin Guay was recently awarded the Founders Affiliate Predoctoral Fellowship by the American Heart Association to begin on January first. The title and the summary of the grant are as follows:
The Role of DAPK2 in Fibroblast Activation in Chronic Kidney Injury
Chronic kidney disease (CKD) is frequently associated with cardiovascular disease and is of particular concern to heart disease, transplant, and diabetic patients. Preliminary studies identify Death Associated Protein Kinase 2 (DAPK2) as a mediator of cell death in the renal interstitial fibroblasts that accumulate in fibrosis associated with experimental CKD, and an enhancer of matrix deposition in an induced CKD model. Following acute nephrotoxic injury, DAPK2 mediates death of these cells, but plays other roles during chronic nephrotoxic exposure. We hypothesize that this enhances the matrix deposition and resultant fibrosis that occur during chronic injury. We propose DAPK2 as a candidate modulator of tubulointerstitial fibrosis associated with CKD, and propose experiments to critically test this hypothesis.
In a series of in vitro experiments we will determine whether DAPK2 is a component of the TGF-beta mediated fibroblast activation pathway , and if DAPK2 functions through non-canonical TGF-beta pathways; In disease model studies using wild type and Dapk2 null mice, we will further define the role of Dapk2 in enhancing renal fibrosis. By understanding the mechanisms that regulate interstitial fibroblast death and activation, we will be able to offer new avenues for therapeutic research that will protect human patients from chronic kidney disease.