Jizhong Cheng Lab

Cardiovascular disease remains the leading cause of death in patients with chronic kidney disease. A major contributor is vascular calcification, a highly regulated biological process characterized by pathological mineral deposition within the arterial wall. Rather than representing passive calcium accumulation, vascular calcification results from active cellular reprogramming in which vascular smooth muscle cells (VSMCs) acquire osteoblast-like characteristics. Although several calcification inhibitors have been identified, the mechanisms through which endothelial cells regulate VSMC calcification remain largely unknown. Our laboratory identified a previously unrecognized protective role for endothelial Jagged1 signaling during CKD-induced vascular calcification. We investigate whether enhancing Jagged1 signaling in endothelial cells preserves endothelial mitochondrial function, maintains production of calcification inhibitors, activates Notch3 signaling in vascular smooth muscle cells, and ultimately prevents CKD-induced vascular calcification. Our long-term objective is to develop therapies that prevent vascular calcification by restoring endothelial function and preserving healthy communication between endothelial cells and vascular smooth muscle cells.

A functional arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, yet nearly half of AVFs fail to mature adequately for long-term use. Despite numerous clinical studies, effective therapies that improve AVF maturation remain unavailable. Our laboratory investigates how chronic kidney disease alters communication between skeletal muscle and the vasculature to influence AVF remodeling and failure. We discovered a novel connection between skeletal muscle wasting and vascular remodeling during CKD. We hypothesize that inhibition of myostatin or YAP1/TAZ signaling suppresses vascular inflammation, fibrosis, and maladaptive remodeling, thereby improving AVF maturation and long-term function. Our goal is to develop targeted therapies that improve vascular access durability for patients receiving hemodialysis by interrupting pathological signaling in the vasculature.