1:00 PM to 2:00 PM | September 11, 2025

Seminar: Targeting RNA with small molecules — Leveraging structure and ensembles for discovery

Forum Hall, Palmer Commons
Audience This is a public event.
In its place at the heart of the central dogma of molecular biology, RNA plays many fundamental regulatory roles, controlling processes such as gene expression, development, metabolism, homeostasis and disease. Coupled with a need for new targets for diseases with no cure, interest in RNA as a target for small molecules has risen dramatically in recent years. However, most technologies to interrogate RNA biology and structure with small molecules lag far behind comparable technologies to study proteins. 
 
In this seminar, John Schneekloth, Jr., Ph.D., will describe his lab's efforts to understand RNA as a target for small molecules, with an emphasis on how detailed understanding of RNA structure and biophysics can lead to important advances in ligand design and potential translational impacts. Topics will include the use of machine learning-based approaches to interrogate RNA-binding chemical space and to study RNA dynamics, how structure can be leveraged in rational design of new ligands for RNA and to explain mechanism of action, how structural ensembles effect ligand binding events and the translational potential of RNA as a target for small molecules.

Speaker

John Schneekloth portrait
John 'Jay' Schneekloth, Jr., Ph.D.
Senior Investigator, Chemical Biology Laboratory
National Cancer Institute

John 'Jay' Schneekloth received his undergraduate degree from Dartmouth College, where he worked with Prof. Gordon Gribble. He then moved to Yale University and obtained a Ph.D. from the chemistry department with Prof. Craig Crews. As a graduate student he studied natural product total synthesis and developed the first cell-permeable PROTAC molecules. He then pursued an NIH postdoctoral fellowship with Prof. Erik Sorensen at Princeton University, where he worked on the development of a new multicomponent reaction and the application of this reaction to the synthesis of analgesic natural products. He returned to Yale in 2009 as a medicinal chemist at the Yale Small Molecule Discovery Center. In 2011, Dr. Schneekloth joined the National Cancer Institute, where his research involves using synthetic chemistry and high throughput chemical biology approaches to develop chemical probes of RNA, with a particular emphasis on targeting RNA with drug-like small molecules.

Hosts

Life Sciences Institute
Department of Biological Chemistry, Medical School