Abstract

One major scientific challenge is to understand biological pathways and to exploit the targets within them for therapeutic development.  Coding and non-coding RNAs both directly cause disease, whether by mutation or aberrant expression.  Akin to proteins, RNA structure often dictates its function in health or dysfunction in disease.  RNA, however, is generally not considered a target for small molecule chemical probes and lead medicines, despite its immense potential.  The focus of our research program is to uncover fundamental principles that govern the molecular recognition of RNA structures by small molecules to enable design of chemical probes that targeting disease relevant RNA structures to perturb and study their function.  

In this talk, I will describe using evolutionary principles to identify molecular recognition patterns between small molecules and RNA structures by studying the binding of RNA fold libraries to small molecule libraries.  The resultant, privileged interactions are computationally mined across the human transcriptome to define cellular RNAs with targetable structure.  Such an approach has afforded bioactive interactions that have uncovered new biology, where the small molecules bind to functional structures within a target RNA.  Recently, we have devised a strategy to imbue biologically silent RNA-small molecule interactions with cellular activity.  In particular, chimeras comprising an inactive small molecule and ribonuclease recruiter trigger targeted degradation of disease-causing RNAs.  These degraders affect the biology of RNA in specific ways in cells and in mouse models of various diseases and can rationally reprogram protein-targeted medicines for RNA.

报告人简介

Positions

• Associate Editor, Journal of the American Chemical Society
• Scientific Advisory Board, The University at Albany The RNA Institute
• Founder and Chair of Scientific Advisory Board, Expansion Therapeutics

Education

• B.S., Chemistry, The University of Maryland, College Park, 1997
• M.S., Physical Chemistry, The University of Rochester, 1999
• Ph.D., Chemistry, The University of Rochester, 2003
• Post Doctoral Fellow: The Massachusetts Institute of Technology and ETH Zürich – Eidgenössische Technische Hochschule Zürich, 2002-2004

Awards and Honors(since 2010)

• Nobel Laureate Signature Award for Graduate Education in Chemistry (with Dr. Alicia Angelbello, 2021)
• Research Program Award(2020-2028)
• The Raymond & Beverly Sackler International Prize in the Physical Sciences(2019)
• BioFlorida’s Weaver H. Gaines Entrepreneur of the Year Award(2018)
• The Barry Cohen Prize(2018)
• Scripps Florida Outstanding Mentor(2017)
• NIH Director’s Pionneer Award(2016)
• Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry(2016)
• Blavatnik Young Scientists Award Finalist(2015)
• David W. Robertson Award in Medicinal Chemistry (2014)
• Excellence Award in the field of Research in Science and Technology. (2013)
• Eli Lilly Award in Biological Chemistry. (2013)
• The American Chemical Society Division of Carbohydrate Chemistry David Y. Gin Award. (2011)
• University at Buffalo, Exceptional Scholar (2011)