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Research Projects

We study pathogenic mechanisms to find cures for kidney diseases

Renal cysts in polycystic kidney disease (PKD) are surrounded by a hypoxic and nutrient-poor microenvironment due to gradual loss of blood vessels and capillaries. How then do the cysts keep growing? Is altered metabolism enough to support cyst epithelial cell proliferation?

We observed large numbers of myofibroblasts that appeared to crowd around the cysts and wondered if they serve a direct role in supporting cyst growth. Our studies showed that cyst epithelial cells in PKD kidneys can stimulate accumulation of myofibroblasts in their microenvironment. We identified a YAP and CCN2 dependent interaction pathway as one of the mechanisms by which cyst epithelial cells simulate myofibroblast accumulation.

research diagram including drawings of mice and cells

What function could myofibroblasts be serving the cysts?  

To test this, we depleted myofibroblasts, which significantly reduced cyst growth in PKD mouse kidneys. Our in vitro and in vivo studies also showed that myofibroblasts directly promote cyst epithelial cell proliferation and cyst growth in PKD kidneys. Thus, myofibroblasts support cyst growth and reducing their numbers could be a novel therapeutic strategy to treat PKD. In a project funded by an NIH R01 grant, we further explore the mechanism by which cyst epithelium and myofibroblasts interact and identify targets to inhibit this vicious cycle.

Read article regarding this project in the Kidney Institute's newsletter.

graphics and cell findings including the text Myofibroblast Depletion Reduces Renal Cyst Growth and Fibrosis in Autosomal Dominant Polycystic Kidney Disease

This new project tests the hypothesis that disruption of the circadian clock stimulates early and accelerated disease progression in ADPKD kidneys. The studies will address an important question of whether circadian disruption by environmental factors or gene modifications drive renal cystogenesis in ADPKD and provide clinical guidance for PKD patients to avoid chronodisruptors. 

drawing of Tubular Epithelial CellAKI is characterized by abrupt loss of kidney function caused by injury to the renal tubules. We study the mechanisms underlying the complex pathophysiology of AKI involving injury and repair and aim to develop effective therapies to accelerate renal tubular regeneration after AKI and prevent fibrosis and AKI to chronic kidney disease transition. Our current studies are focused on examining how renal interstitial myofibroblasts affect tubular epithelial regeneration after AKI.

We have identified a pathogenic role of vasopressin type-2 receptor (V2R) signaling in RCC, and repurposed the V2R antagonist and FDA approved drug Tolvaptan as a therapy for RCC.   Oncogene 2020, PMID: 31616061

US Patent No. 11,110,098. Methods and Medicaments for the Treatment of Renal Cell Carcinoma.

Ongoing studies test the hypothesis that V2R mediated cell signaling in RCC tumor cells, acting via HIF1α and CCL20 stimulate secretion of factors that regulate cancer associated fibroblasts and tumor growth.

Internal Medicine

University of Kansas Medical Center
Internal Medicine
Nephrology & Hypertension Division
Mailstop 3018
3901 Rainbow Boulevard
Kansas City, KS 66160

Nephrology Fellowship
Transplant Fellowship

General Questions:
913-588-4852
Fellowship:
nephfellowship@kumc.edu