January 05, 2024

Team Action for Scientific Solutions: Polycystic Kidney Disease Group

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In science, collaboration is about sharing information, resources, and ideas. The partnership allows faculty to combine their knowledge and resources to form new ideas that might not have been possible by working alone, which leads to better results for everyone involved.Bradley YoderBradley Yoder, Ph.D.

Several groups across the Heersink School of Medicine come together regularly to promote team science in their respective areas of expertise. The Office of Research for the Heersink School of Medicine highlights the work of these groups in its Team Action for Scientific Solutions (TASS) series.

The Heersink School of Medicine communications staff sat with Bradley Yoder, Ph.D., professor and chair of the Department of Cell, Developmental and Integrative Biology, to gain insight into the Polycystic Kidney Disease (PKD) Group.

Q: What is the PKD group?

The main objective of the PKD group is to develop and disseminate a wide array of resources to the PKD research community, including biomaterials, antibodies, DNA vectors, and animal and cell-based genetically engineered models. The goal is to accelerate the discovery rate in PKD, leading to better treatment and a cure.

Q: How did you become involved in this area?

I attended a Southeast Developmental Biology Meeting in the last year of my doctoral studies in 1993, where I attended a seminar by Dr. Rick Woychik. He described a new transgene insertion-induced mouse mutant that had pathologies in multiple tissues (extra toes, cleft palate, extra teeth, pancreatic abnormalities, sterility, blindness, etc.) but developed prominent cysts in the kidney and liver that resembled the recessive form of PKD. That was one of the first mouse models developed to study PKD. His group identified the gene, now called IFT88, responsible for the phenotypes but had yet to learn what the protein did. At the meeting, I arranged for a postdoctoral training position in his lab and moved to Knoxville, TN, to figure out its function. This objective was not fully realized until I accepted my assistant professor position at UAB. We found that IFT88 is an evolutionarily conserved intraflagellar transport protein (IFT) required for building and maintaining a small structure on cells called the cilium. The connection between the IFT88 mutant mouse and human PKD was finally realized when it was found that the proteins associated with PKD in humans, called polycystin-1 and polycystin-2, localize and function in the cilium.

Q: What prompted the development of this program?

The PKD research interest group originated nearly 20 years ago when Dr. Guay-Woodford gathered a group of 4-5 UAB faculty members with common research and clinical interests in cystic kidney-related disorders. Today, it has expanded to include multiple faculty and trainees across departments at UAB. It regularly meets to discuss recent findings and new research directions to better understand this disease.

With seed funding from the Department of Medicine, we organized the group to successfully compete to become one of the four original national NIH PKD Centers. The UAB center was unique because of our focus on the recessive form of PKD that mainly affects children rather than the dominant form of the disease that affects adults. We have renewed this center three times and are currently the longest standing NIH funded PKD center.

In the most recent renewal, the NIH restructured the centers from a P30/P50 mechanism into a U54 as a national consortium focusing on resource development for the PKD research community. The U54s are more of a collaborative arrangement with the NIH, which acts as a partner in determining the direction of the center. The three current centers are at UAB, the University of Maryland, and the University of Kansas Medical Center. We are collectively known as the Polycystic Kidney Disease Research Resource Consortium (PKD RRC). The University of Maryland serves as the coordinating site that oversees the consortium.

Q: What activities are offered in this program?

In addition to resource development and dissemination, the PKD RRC organizes patient resources, educational programs, a seminar series, an annual PKD symposium, mentorship activities for junior investigators, and a pilot and feasibility awards program to support early-stage investigators interested in PKD or for established investigators not currently working in PKD to transition toward PKD related research.

Q: What is innovative about this program?

The PKD RRC is providing PKD research with access to hard-to-obtain PKD patient materials, establishing rigorously controlled cell models to study PKD, including human induced pluripotent stem cells with patient PKD mutations, new mouse models engineered to mimic mutations identified in PKD patients, new antibodies and endogenously tagged polycystin proteins to detect the polycystin proteins in cells and in vivo in human and mammalian kidneys. The PKD RRC is open to suggestions or recommendations for new resource requests that are deemed to advance PKD research.