Institution: The Research Institute at Nationwide Children's Hospital
Grant: Norman Siegel Research Scholar Grant (2019)
Project Title: Therapeutic Urothelial Remodeling: A Novel Strategy to Limit Obstructive Kidney Injury
How would you sum up your research in one sentence?
My laboratory studies ways to preserve renal function in children with urinary tract obstruction.
Provide a brief overview of the research you will conduct with help from the grant.
As a pediatric nephrologist, I am frustrated by the lack of specific therapies for patients with congenital anomalies of the kidney and urinary tract, which account for the majority for childhood CKD and ESRD. During my fellowship training under the guidance of Dr. Kirk McHugh, we discovered that congenital obstruction leads to reorganization of a seldom-studied cell population: the renal urothelium. This remodeling results in increased production of Uroplakin (Upk) plaque, an essential protein network that promotes urothelial cell compliance and maintains the urine permeability barrier. This discovery led to the hypothesis that urothelial remodeling limits obstructive nephropathy by increasing Upk plaque deposition. This grant tests the hypothesis that signaling pathways implicated in urothelial cell proliferation and Upk synthesis can be harnessed therapeutically to promote Upk plaque production and attenuate obstructive kidney injury.
What inspired you to focus your research in this area?
When I was a fourth year medical student, I cared for a boy with respiratory failure and renal dysplasia due to severe urinary tract obstruction. The challenges of caring for such patients led me to choose nephrology and congenital urinary tract obstruction as my clinical research focus.
What impact do you hope your research will have on patients?
The ultimate goal of this research is to develop medical management strategies to stabilize kidney structure and preserve kidney function in the face of chronic obstruction. Ideally, such therapies will be administered during fetal development, when urinary tract obstruction compromises both kidney and lung development. Such medical interventions would serve as temporizing measures until definitive surgical intervention can occur, as adjuncts to surgical intervention, or - potentially - entirely in place of surgery altogether.
What are your short and long-term career goals?
The immediate goal of the grant is to establish that existing, FDA-approved drugs can be repurposed to safely and effectively promote urothelial remodeling in small animal models of urinary tract obstruction. The long-term goal of this research is to develop effective interventions that limit kidney injury as a consequence of urinary tract obstruction (UTO).
What has surprised you most about your career?
The ways in which encounters with patients can inspire and direct the work we do in the lab.
What are the major challenges facing nephrology research today?
We need to inspire the best and brightest young people to study the kidney. There is so much more to discover about this organ, and the tools to dissect mechanisms of kidney disease are more sophisticated now than ever.
In one sentence, please describe the importance of having grant funding available through the ASN Foundation.
I am so grateful for the opportunity to receive this Career Development Grant from the ASN Foundation. This funding enables my laboratory to perform a set of experiments that will test the hypothesis that therapeutic urothelial remodeling during UTO is feasible and effective as an approach to stabilize renal function and prevent renal injury.
Something you may not know about me is…
I enjoy mowing my lawn.
In my free time I like to…
Spend time traveling, exercising, and simply relaxing with my wife and four children.