Shuai Wu


Dr. Sohn’s lab studies various biological stress-sensor proteins, including mammalian cyclic GMP-AMP (cGAMP) synthesis (cGAS). cGAS plays a crucial role in activating innate immune responses against cytosolic dsDNA in mammals. My research on cGAS involved solving multiple crystal structures of cGAS bound to different substrates, dinucleotide intermediates and divalent metals at various catalytic stages. Our structural findings, combined with biochemical measurements, redefined the molecular mechanism by which cGAS generates 2’-5’/3’-5’-linked cGAMP. The novel structures and mechanistic insights from our study have the potential to guide researchers in developing small molecule therapeutics targeting different active states of cGAS.

Questions & Answers

Why did you choose Johns Hopkins for your work?

I chose Johns Hopkins for my postdoctoral training owing to its outstanding reputation as a research institution renowned for pioneering and groundbreaking research. As it turns out, my choice proved to be the right one.

What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?

I want to express my sincere gratitude to the Young Investigators’ Day Committee for honoring my research with the Alfred Blalock Research Award. Receiving this award brings me immense honor and happiness. This recognition serves as a strong motivation for me to continue my academic pursuits.

What contributed to your project’s success?

Being part of Jay Sohn’s lab team is an absolute privilege. Without Dr. Sohn’s guidance and unwavering support, my project wouldn’t have been feasible. I’m particularly thankful for the numerous enlightening discussions with Jay throughout the project and the freedom to explore different possibilities. Moreover, Dr. Sandra B. Gabelli’s oversight of crystallographic data collection and processing, coupled with remote access to the National Synchrotron Light Source II, are also vital components for the project’s success.

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?

I see Young Investigators’ Day as an excellent platform for recognizing the substantial dedication invested into research endeavors for award recipients. Furthermore, the award cultivates a valuable network among young researchers at Hopkins for communication and collaboration.

What has been your best/most memorable experience while at Johns Hopkins?

 

Upon observing the electron density of the cGAS reaction intermediate pppGpA on Coot, I was struck by the precision and elegance of the enzyme. This experience highlighted to me the profound capability of X-ray crystallography in elucidating enzymatic reactions.

What are your plans over the next year or so? Graduating, looking for faculty positions, etc.?

I would like to apply for a faculty position and establish a lab to continue my research interest in unraveling the mechanism of biological stress-sensor pathways and autophagy.

Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences?

I like music, which may have been inherited from my father. I enjoy exploring various musical instruments and playing guitar and harmonica from time to time.