Dan Fabris, Professor and Schwenk Distinguished Chair, Department of Chemistry, University of ConnecticutExploring Ligand Interaction with Viral RNA by Mass Spectrometry
The Department of Chemistry Presents, via Online Zoom and In-Person Presentation: Dr. Dan Fabris, Professor and Harold S. Schwenk, Sr. Distinguished Chair, Department of Chemistry, University of Connecticut
The multifaceted biological functions carried out by RNA make this biomolecule an ideal target for drug discovery, as well as a putative therapeutic agent in its own right. Native mass spectrometry (MS) enables the investigation of the specific interactions between RNA and other nucleic acids, proteins, and small-molecule ligands, which define its functions and, thus, its therapeutic potential. With proper precautions and experimental design, this platform can be effectively employed to obtain information that may not be readily accessible by traditional biophysical approaches. Some applications rely on the mass determination of all species at equilibrium in solution to obtain the sought-after information. Others capitalize on the coupling with ion mobility spectrometry (IMS) to investigate the effects of binding on RNA conformation and structural stability. The talk will discuss the caveats and illustrate possible strategies for overcoming typical challenges. The soaring interest in RNA exhibited by big pharma and biotech alike will be expected to significantly increase the diffusion of these types of applications and to spur the development of new strategies for the investigation of the structure and dynamics of nucleic acids.
Dr. D. Fabris is the Harold S. Schwenk Sr. Distinguished Chair in Chemistry and a Professor in the Department of Chemistry of the University of Connecticut. As a student at the University of Padova (Italy) in the late Eighties, he was introduced to mass spectrometry (MS) by Dr. P. Traldi at the National Research Council in Padova, while working on a thesis project aimed at the characterization of the degradation products of preservatives used in cosmetics. In 1992, a move to the University of Maryland Baltimore County (USA) to work with Dr. C. Fenselau involved a conspicuous change of direction towards the development of approaches for protein analysis and the investigation of their interactions with ligands and metals. Starting in 1999, as a faculty at University of Maryland Baltimore County, he established an independent program aimed at the development of enabling MS technologies for the investigation of the structure-function relationships in viral RNA systems. In 2010, he moved to the University at Albany (SUNY) to become one of the founding members of The RNA Institute. At University of Connecticut since 2020, his laboratory specializes in the development of MS-based technologies for epitranscriptomics analysis and the investigation of the effects of RNA post-transcriptional modifications on structure and dynamics of viral RNA.
His research program is dedicated to the investigation of the structure-function relationships in RNA involved in infectious diseases and cancer. The interface between Chemistry and Biology offers a wealth of opportunities for extraordinary breakthroughs. In this direction, his group has been developing new cutting-edge approaches to investigate essential process in the lifecycle of RNA viruses, such as HIV-1, Zika, Hepatitis C, and now SARS-CoV-2, which pose dire biomedical challenges with enormous socioeconomic impact. His group is currently exploring the interactions between drugs of abuse and HIV-1 morbidity and evaluating the potential of essential RNA structures present on the genome of SARS-CoV-2 as effective targets for the development of new antiviral therapies.
Online and In-person