Abstract: Our group is broadly interested in understanding how metazoan cells fold complex proteins, and how the need to fold those proteins impacts their ability to evolve. The development of chemical genetic techniques to allow precision engineering of proteostasis network composition and activities will be discussed. Progress in understanding the roles of proteostasis in evolution at the host-pathogen interface will also be presented. For example, we discovered that the biophysical consequences of host chaperone depletion strongly reduce the ability of influenza to escape innate immune system factors. Key mutations that helped drive the pathogenicity of the 1918 pandemic flu rely on host chaperones for their fitness. Building on these findings, recent efforts to understand how chaperones shape the evolution of oncoproteins, such as p53, will be summarized. The connections drawn between host proteostasis and viral evolution have implications for issues including viral host-switching, which we have explored in the bacteriophage setting, vaccine development, and the design of improved chemotherapeutics. 

Biography: Matt Shoulders graduated summa cum laude from Virginia Tech with a B.S. in Chemistry in 2004. He earned his Ph.D. in Chemistry from the University of Wisconsin–Madison in 2009, advised by Prof. Ron Raines. Following an American Cancer Society Postdoctoral Fellowship with Profs. Jeffery Kelly and Luke Wiseman at the Scripps Research Institute in La Jolla, California, Shoulders joined the MIT Department of Chemistry as an Assistant Professor in 2012. He was promoted to Tenure in 2019, and is now the Class of 1942 Professor of Chemistry.

The Shoulders Laboratory is interested in (1) understanding how cells fold proteins and (2) using the tools of evolution to understand proteostasis and develop next-generation biomolecules with important applications in medicine and agriculture. Prof. Shoulders has received numerous awards recognizing his lab’s work, including the National Institutes of Health Director’s New Innovator Award, the National Science Foundation CAREER Award, and the Camille Dreyfus Teacher-Scholar Award. He was also named an American Cancer Society Research Scholar and the 56th Edward Mallinckrodt Jr. Foundation Faculty Scholar. Most recently, Prof. Shoulders received the Ono Pharma Foundation’s Breakthrough Science Award. In 2018, Shoulders received MIT’s Committed to Caring Award for Outstanding Graduate Student Mentoring. Shoulders was named a MacVicar Faculty Fellow in 2022, recognizing outstanding and sustained contributions to undergraduate education and mentoring at MIT.