Mochel lab will utilize canine, feline kidney organoids to advance knowledge of CKD 

Dr. Jon P. Mochel

Dr. Jon P. Mochel has been appointed the Diane L. Wynocker Professor for Advancing Canine Kidney Disease Research in the University of Georgia College of Veterinary Medicine. Mochel, director of the Precision One Health Initiative, leads a team of scientists developing novel research models using lab-grown mini organs, called organoids. 

The Mochel lab grew a canine kidney organoid about four years ago and recently established what they believe to be the first feline kidney organoid model in the world. Although organoids are simplified versions of the actual organs and tissues they’re derived from, they give researchers a cellular level view of the development and progression of diseases. They also make it possible to test the efficacy of drug candidates proposed as treatments prior to clinical trials. 

The lab’s CKD research has two main components. “The first is to better understand what are the drivers of chronic kidney disease pathogenesis, how it actually changes over different stages and becomes irreversible,” Mochel said. 

“The main clinical need remains unmet: as of today, there is no FDA-labeled drug approved to treat or slow the progression of chronic kidney disease (CKD) itself in dogs or cats in the U.S.” 

The lab’s advances with organoids dovetailed with donor Wynocker’s desire to encourage research into canine kidney disease at UGA, which led to the endowed professorship. 

“It is my hope, that by establishing this professorship with Dr. Mochel at the helm, we can utilize additional resources to broaden the scope of chronic kidney disease research,” Wynocker said. “We must explore all possibilities to make progress in treating this disease.” 

One donation leads to others 

Wynocker lost three Shetland Sheepdogs – Lambert, Timmer and Piper – to CKD. She became interested in the college’s research on the topic after Piper died and her veterinary practice made a donation to UGA VetMed in memory of Piper. That donation inspired her to make her own contribution, creating the Lambert, Timmer and Piper Wynocker-Beckwith CKD Research Fund. The fund is currently supporting studies led by Dr. Bianca Lourenço and Dr. Jane Hua-Chen Huang in the Department of Small Animal Surgery. 

Two of Diane L. Wynocker’s beloved shelties.

Kidney disease is a common ailment in dogs, but unlike humans and even cats, dogs do not have a kidney transplant option. The disease can be detected in cats in the early stages and typically progresses slowly. But CKD in dogs is past the point of treatment by the time it’s diagnosed. 

“Right now, we maintain a dog’s life to a certain extent, however, let’s try and do something where we can catch it earlier and have a better prognosis,” Wynocker said. 

A journalist with a healthy curiosity about the mechanics of the lab’s research, Wynocker is a unique benefactor beyond her personal experience with canine CKD. “She wants to look under the hood and see what we’re doing, which is really exciting for us,” Mochel said. “She can be part of the journey with us.” 

Laying the groundwork

Christopher Zdyrski, PhD

The “us” in the lab is Christopher Zdyrski, PhD, lab director, and Hannah Nicholson, a graduate student who grew the feline kidney organoids. Zdyrski laid the groundwork for the study four years ago when he grew canine kidney organoids during his PhD. That specimen was placed in cold storage while the lab sought research funding. It was retrieved from cold storage last year when the lab was endowed for pharmaceutical studies. 

Nicholson’s initial focus is on studying the canine and feline organoids and identifying the components of the mini organs growing in the lab’s culture dishes. Sequencing is also being done to definitively identify the cells in the dish. 

“Better understanding the composition of the organoids in this early stage of the project is going to kind of catapult everything else. If we’re only mimicking a certain part of the kidney, then our targets are going to be associated with that part. So, I hope that we will have a better understanding of the disease as a whole at the tissue level,” she said.

Hannah Nicholson

Projecting an image of a canine organoid on her computer screen, Nicholson described her findings so far, pointing to both epithelial cells in the organoids and fibroblasts (crucial cells in the kidney that are also key in the development of CKD), which were present because the sample was grown from tissue in a dog with CKD.

One helps the other 

Chronic kidney disease is marked by gradual loss of kidney function over time. In humans, it can be caused by diabetes, high blood pressure, heart disease, or heredity. In both cats and dogs, CKD is commonly diagnosed in older animals and is frequently detected at moderate-to-advanced stages because early disease is often clinically silent. In cats, the underlying etiology is commonly not identified and chronic tubulointerstitial disease predominates, whereas in dogs CKD reflects a more heterogeneous set of primary renal disorders (e.g., glomerular, tubulointerstitial, congenital/hereditary, or inflammatory/infectious disease). Prognosis varies substantially by IRIS stage and key modifiers such as proteinuria and hypertension; reported survival times in cats are often longer than in dogs in some cohorts, but outcomes are strongly phenotype- and stage-dependent. 

While CKD pathogenesis and progression differ in each species, understanding one will further the understanding of the other. 

“We’re not treating canine and feline CKD organoids as two separate projects,” Zdyrski said. “Instead, we’re building a comparative pipeline where each species informs the other, shared mechanisms can be identified, and species-specific biology is tested explicitly. Progress in one model helps de-risk and accelerate the other.” 

Nicholson said she’s hopeful the project will lead to the discovery of biomarkers or druggable targets that allow detection and treatment of the disease earlier, thereby extending the lives of canine and feline patients.  

“Because that’s really the crux of it all: if we can’t intervene early on, it’s really hard to do so late in the disease progression.”

The Mochel Lab, from left: Christopher Zdyrski, Dr. Aleksandra Pawlak, Dr. Jon Mochel, Hannah Nicholson, Michael Catucci and Luc Lefevre