Local acidosis causes tissue damage, and pain and is one of the hallmarks of ischemia, cancer and inflammation. However, the molecular mechanisms of the cellular response to acid are not fully understood. Besides the cation-conducting, acid-sensing ion channels (ASICs), the acid also activates a chloride (Cl−) conductance in a wide range of mammalian cells. Although the electrophysiological properties of the proton-activated Cl− channel have been described in detail, its molecular identity has remained elusive. This gap makes it impossible to elucidate its precise biological function and potential contributions to the pathogenesis of acidosis-related diseases.
Taking advantage of the powerful functional genomics screen established in our lab, we identified a novel membrane protein, named PAC (also known as TMEM206), as the proton-activated Cl− channel. PAC mRNA is expressed in diverse tissues, with the highest level detected in the brain. Knockout of mouse PAC abolishes the channel activity in neurons and protects them from acid-induced cell death. Importantly, PAC KO mice exhibited significantly smaller brain infarct volume when subjected to a middle cerebral artery occlusion (MCAO) stroke model. Therefore, PAC may represent a potential drug target for stroke and other acidosis-associated diseases.
This work has been done in the laboratory of Zhaozhu Qiu, Ph.D., in the Department of Physiology.
Questions & Answers
Why did you choose Johns Hopkins for your work?
Johns Hopkins has a highly collaborative and supportive scientific environment and world-class biomedical research. It has a longstanding commitment to career advancement for postdocs.
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
It is truly a great honor for me to be a recipient of the Paul Ehrlich Research Award. It is also a great motivator for me to continue my research and eventually lead my own scientific career.
What contributed to your project’s success?
I am fortunate to say that my past scientific achievements, which were acquired not only through my passion and dedication to science but also under the excellent guidance and unfailing support of my exceptional mentor, Dr. Qiu. The Qiu Lab has a dynamic young group of intellectually-charged researchers and a highly stimulating environment that are extremely interactive and always supportive. I certainly would not have been able to do this alone and am grateful for everyone in the lab.
What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins?
Young Investigators’ Day recognizes and highlights the contributions of students and fellows, and encourages them to pursue their scientific achievements in the future.
What has been your best/most memorable experience while at Johns Hopkins?
I have been working at Hopkins for more than four years. There are so many exciting and excellent moments such as figuring out the important scientific questions, the acceptance of our papers, and collaboration with wonderful people. After the tragic loss of one of the best colleagues and friends in the lab, I would like to appreciate that every day in the lab is the most memorable experience.
What are your plans over the next year or so?
I am turning the fifth year of my postdoctoral research. I am going to finish up current projects and look for a faculty position to start my independent research career.
Tell us something interesting about yourself.
I really enjoy being with my wife and kids in my free time. Crab hunting with the kids along the coast is my favorite thing here.