Jackson Lab
Congenital Urinary Tract Obstruction (UTO) is the leading cause of pediatric chronic kidney disease (CKD). Apart from surgery to relieve the UTO, there are no specific medical interventions that prevent or limit progressive kidney injury. Furthermore, adults with a history of childhood UTO are at increased CKD risk. Thus, there is an unmet clinical need for therapies that can protect the kidney and preserve long-term kidney function.
The Jackson Lab uses congenital and acquired UTO models to investigate the kidney’s response to obstruction. They discovered renoprotective bladder-like remodeling in the kidney’s urothelium during congenital and acquired UTO. Specifically, UTO triggers renal urothelium remodeling characterized by increased uroplakin (Upk) expression. Since UPK is critical to forming a compliant and watertight, barrier in the bladder urothelium, increased renal UPK represents an ideal functional adaptation during UTO. Indeed, kidney dysfunction and mortality are accelerated in UPK-deficient mice with congenital UTO. Therefore, discerning the signaling pathways that promote UPK expression form the foundation for innovative UTO therapies.
Our Projects
The Jackson Lab uses the Megabladder mouse to model congenital UTO. These mice possess a bladder specific smooth muscle defect and manifest a functional UTO. They use unilateral ureteral obstruction (surgical occlusion of the ureter) to model acquired UTO. Additionally, the Jackson Lab uses cutting-edge organoid models to investigate renal urothelium development and remodeling. They genetically and pharmacologically manipulate the urothelium to enhance its renoprotective properties. Their findings form the foundation for the development of novel therapies aimed at protecting the obstructed kidney and mitigating obstructive kidney disease.
Featured Publications
Ongoing Research Support
| Funding | Research | Role |
| K01-DK-126991 | Defining the renal urothelium progenitor and its regulation during development and repair |
Principal Investigator |
| R01-DK-125469 |
Novel roles for urothelium during urinary tract obstruction |
co-Investigator |
| R01-DK-127589 |
Prune Belly Syndrome: Mechanisms of Filamin A Mutations | co-Investigator |
| R01-DK-128088 |
Insulin Signaling Activates Urothelial Defenses to Reduce Urinary Tract Infection Susceptibility |
co-Investigator |
| T35-DK-129192 |
Student Urinary Tract Program in Education and Research (SUPER) Summer Training Program |
Collaborator |
| R25-DK-126639 |
Nephrology and Urology Workforce Pipeline |
Collaborator |
| K08 ES-034821 |
Bladders and biomes: Environmental compounds as modifiers of microbiomes, metabolomes, and urothelium |
Collaborator |
| Intramural |
Toward a Therapeutic Intervention for Urinary Tract Obstruction - An investigation of Pparg signaling in renal urothelium |
Mentor |
| Intramural |
Urothelial Mechanoreceptors in Urinary Tract Obstruction - An investigation of Piezo1 in renal urothelium remodeling |
Mentor |
Join Our Team!
The Jackson Lab is growing. If you are interested in joining our team as a gap year trainee, research intern, research assistant, etc., please send a cover letter and a CV/Resume to Ashley.Jackson@NationwideChildrens.org.
