Name: Qinzhe Wang, PhD

Institution: The University of Utah

Grant: 2020 Jared J. Grantham Research Fellowship

Project Title: Cryo-EM Structures of Polycystic Kidney Disease Proteins

How would you sum up your research in one sentence?

• My research focuses on elucidating structure and function of the polycystic kidney disease proteins, namely polycystin-1 (PC-1) and polycystin-2 (PC-2), with goals of revealing pathogenic mechanisms of autosomal dominant polycystic kidney disease (ADPKD), and ultimately, facilitating development of novel therapies.

Provide a brief overview of the research you will conduct with help from the grant.

• The polycystin-1 (PC-1) receptor and polycystin-2 (PC-2) ion channel play pivotal roles in the development, structural maintenance and functions of kidney. Mutations that render PC-1 or PC-2 defective cause a common life-threatening autosomal dominant polycystic kidney disease (ADPKD). PC-2 traffics to primary cilia where it alone acts as a cation channel, and additionally assembles with PC-1 to form a receptor/channel complex of as-yet undetermined biophysical properties and unclear physiological functions. The goal of the proposed research is to illuminate the activation mechanisms of PC-2, which will help to develop novel therapeutic strategies aimed to rectify disease mutations and treat the root causes of ADPKD.

What impact do you hope your research will have on patients?

• ADPKD is a common, monogenic multi-systemic disorder with significant individual and societal burdens. I hope that my research can be exploited for future drug development to cure ADPKD patients.

What are your career goals at the end of the grant period? Five years out? Ten years out?

• My long-term career goal is to establish a research lab in academia so that I can contribute to enhancing our knowledge of biomedical sciences, and ultimately helping patients who suffer from various diseases. I envision that an in-depth understanding of disease pathology at biochemical and structural levels will eventually translate into therapeutic breakthroughs for treating patients.

What inspired you to focus your research in this area?

• I have been trained as a biochemist since I was an undergraduate and I always aspire to contribute to biomedical research that would improve the healthcare of patients. I studied structures and functions of membrane proteins involved in multiple human diseases in graduate school. To gain more training in membrane protein structural biology, I joined Dr. Erhu Cao’s lab at the University of Utah as a postdoc fellow, when I learned crucial roles that PC-1 and PC-2 play in cystic kidney diseases. I decided to pursue nephrology research focusing on cystic kidney diseases because there are so many people suffer from ADPKD and ARPKD every single day.

What are the major challenges to beginning a career in nephrology research today?

• A crucial goal of almost every branch of biomedical sciences is to understand how various biological processes operate at molecular or atomic level in normal and diseased states. Current nephrology research is no exception to this trend and will certainly benefit from researchers who have strong training in biochemistry, molecular biology, and structural biology. This is an era of knowledge explosion. It puts more demands of time and resources on individuals who are just starting their careers.

In one sentence, please describe the importance of having grant funding available through KidneyCure.

• The Jared J. Grantham Research Fellowship will not only support my current research, but also help me launch an independent academic career in mechanistic studies of renal physiology and diseases.

Something you may not know about me is…

• I am a good bioinformatician.

In my free time I like to…

• Go hiking.