Published October 3, 2019
Researcher: Yong Yu, Ph.D. | St. John’s University
PKD Foundation (PKDF): How did you first get involved in PKD research?
Yong: When I was working as a postdoc in Dr. Jian Yang’s lab at Columbia University, I was trying to crystallize protein fragments from a group of proteins called transient receptor potential (TRP) ion channels to solve their molecular structures. One protein fragment gave me beautiful crystals, and we were able to solve its structure. The protein fragment turned out to be the C-terminal coiled-coil domain of the polycystin-2 (PC2) protein which forms a trimer. The subsequent fundings led to our discovery showing that the polycystin-1/polycystin-2 (PC1/PC2) complex has a unique 1 (PC1): 3 (PC2) subunit stoichiometry and led to the start of my own journal in PKD research.
PKDF: What are you working on?
Yong: Currently, the PKD research in our lab is focusing on understanding the molecular mechanism of the assembly, function, and regulation of the polycystin proteins PC1 and PC2 (the protein products of PKD1 and PKD2 genes that are mutated in ADPKD) and their function defects caused by pathogenic mutations. The long-term goals of our lab are to understand the biological functions of these proteins and their crosstalk with other functional partners in the cell and to determine PKD pathogenic pathways when they are mutated.
PKDF: What would you like the patient community to know about your research?
Yong: Although the link between the mutations in PKD1 and PKD2 and ADPKD was established more than two decades ago, the molecular function of these proteins and why their malfunction leads to cyst formation in the kidney are still largely unknown, mainly due to the lack of a reliable functional assay. Recently, our lab developed a series of gain-of-function (GOF) mutants of the PC2 protein. These mutations lock the protein at a constitutively activated conformation and allow us to functionally study the PC1/PC2 complex channel by directly recording their ion channel activity. Our results show that both PC1 and PC2 proteins work tightly together to form the functional channel complex, which plays essential roles in conducting ions, including Ca2+, across the cell membrane. This role may be essential for keeping the normal development of the kidney and preventing cyst formation.
PKDF: Do you have a personal connection to PKD?
Yong: One undergraduate student who worked in my lab has PKD. He was diagnosed when he served in the U.S. Air Force. He came to St. John’s University to study physics after finishing his military service. After working in my lab for two years, he went to the University of Pennsylvania to pursue his Ph.D. degree in biophysics.
PKDF: What excites you most about this research?
Yong: In the lab, we are trying to understand how proteins function as molecular machines. We use equipment and apply techniques to detect their structures and monitor their activities, even in single-molecule level with the patch-clamp method. The recent advances in structural biology and single-molecule imaging allow us to see them in action directly. All of these are very exciting but knowing that understanding how these tiny molecules work can help us to understand the disease and potentially help patients makes me most excited in doing this research.
PKDF: What are some of your personal interests outside of research?
Yong: I enjoy a lot of other things outside of the lab, such as photography, hiking, traveling, reading, and visiting museums. In day-to-day life, I spend most of my free time during the weekends with my family.
PKDF: Anything else you’d like to share?
Yong: I met a lot of PKD patients and their family members during last year’s PKD Connect Conference organized by PKD Foundation. I was deeply touched by their enthusiastic support of our research and their eagerness to see more progress in developing new treatments. PKD research, just like research on many other diseases, is not easy. However, with many years of hard work from the whole PKD research community, we have arrived at the right place at an exciting time for this field. I believe we will be able to see more and more important breakthroughs in the near future, which will hopefully lead to a cure for PKD.
PKD Foundation is the largest private funder of PKD research in the U.S. Since 1982, we’ve invested close to $50 million in more than 1,300 research, clinical and scientific grants, fellowships and scientific meetings. Each year, The Foundation identifies and supports the work of scientists and researchers from around the world who look for ways to treat and eventually cure PKD.
Our vision is to end PKD. Donations help fund necessary research that leads to more effective treatments and ultimately a cure for PKD.