Anna Marie Pyle is Professor of Molecular, Cellular and Developmental Biology and Professor of Chemistry at Yale University and she is a Howard Hughes Medical Institute Investigator. Dr. Pyle obtained her undergraduate degree in Chemistry from Princeton University and received her Ph.D. in Chemistry from Columbia University in 1990, where she worked with Professor Jacqueline K. Barton. Dr. Pyle was a postdoctoral fellow at the University of Colorado in the laboratory of Thomas Cech. Dr. Pyle formed her own research group in 1992 in the Department of Biochemistry and Molecular Biophysics at Columbia University Medical Center. In 2002, she moved to Yale University, where she leads a research group that specializes in determining the structure and function of large RNA molecules and protein enzymes that operate on RNA. Dr. Pyle teaches the undergraduate Molecular Biology course at Yale, she serves on the Yale University Budget Committee and University Science Strategy Committee. Dr. Pyle has been a chair and active member of numerous NIH study sections. She serves on the Science and Technology Steering Committee and the NSLS-II Biology Beamline Advisory Team at Brookhaven National labs. Dr. Pyle is President-Elect of the RNA Society and she is on the scientific advisory board of Arrakis Pharmaceuticals. Dr. Pyle is the Co-Editor of Methods in Enzymology and serves on the editorial boards of eLife and other journals. Dr. Pyle is the author of over 170 publications and has mentored more than 40 graduate students and postdocs.
The Pyle lab studies a large family of mechanical enzymes that hydrolyze ATP upon binding RNA (known as helicase Superfamily 2, or SF2 proteins). Some of these enzymes act as nucleic acid unwinding motors, while others undergo ATP-dependent conformational changes upon binding viral RNA, thereby leading to a signaling cascade that induces an immune response. We use a combination of experimental biochemistry, cell biology and crystallography to study the functional properties of these proteins. Recent studies have focused on structures and mechanism of RIG-I and related antiviral sensors. We solved the first crystal structures RIG-I, thereby defining the unusual molecular architecture and RNA recognition properties of the RLR subfamily (which includes RIG-I, the related MDA-5 and LGP-2 innate immune sensors, and the small RNA processing enzyme Dicer) (see papers by Luo et al, 2011-2013). We conducted complementary thermodynamic analyses to dissect the energetic basis for binding and detection of viral RNA by RIG-I (Vela et al, 2012) and we have elucidated the role of ATP in RIG-I mediated signaling and (Kohlway, 2013, Rawling 2015 and Fitzgerald 2017). Our structural and biochemical studies have led to the development of specific RIG-I agonists that specifically control the function of this receptor in-vivo (Linehan, 2018). We are using these findings to develop new therapeutic strategies for the treatment of viral infection, cancer and and autoimmunity.