Upcoming Seminars & Events

Professor Nicholas Ball
Department of Chemistry
Pomona College

Activating Excellence Through Chemistry

Dr. Nicholas Ball is an Associate professor of Chemistry at Pomona College. In this talk, Dr. Ball will provide an overview of his scientific contributions and highlight his own journey navigating science as a Black, queer person. He will discuss how the intersections of his Black queerness have manifested in an abundance mindset and practice that aims to provide accessible, inclusive training grounds for students while pushing the frontiers of science.

Nicholas Ball

Prof. Nicholas Ball grew up in Chattanooga, TN. He received his B.A. in Chemistry at Macalester College in 2005. He completed his Ph.D. in 2011 under Prof. Melanie Sanford at the University of Michigan, working on C–F and C–CF3 bond formation using high- oxidation-state palladium. In 2010, he headed to the California Institute of Technology to pursue his postdoctoral studies with Prof. David Tirrell as an NIH Postdoctoral Fellow. Prof. Ball started as an ssistant Professor at Amherst College in 2013. In 2015, Prof. Ball joined the faculty at Pomona College and is now an Associate Professor of Chemistry with tenure. His current research focuses on developing new methods to make and use sulfur-based molecules for drug targets, biological chemical probes, and materials science. His lab’s work involves making molecules, machine learning, and computational chemistry. His work features collaborations with industry and internationally, as well as with professors at other predominantly undergraduate institutions. Prof. Ball’s honors and awards include the Henry Dreyfus TeacherScholar Award, 2022 Chemical and Engineering News LGBTQ+ trailblazer, and a two-time Wig Distinguished Professor awardee (2018 and 2024). His research has been funded by NIH, NSF, and the American Chemical Society.

Join us for a reception at Fraser Hall after the seminar, from 5–7 p.m.!

Hosted by Professor Courtney Roberts

Professor Nicholas Ball
Department of Chemistry
Pomona College

Sulfur Fluoride Exchange (SuFEx) as a New Tool in Drug Discovery

Why are drugs so expensive? One reason is that it takes scores of researchers and resources to discover and make them. Sulfur(VI) compounds represent over 30% of all sulfur-based FDA- approved drugs. Their shared S–O double-bond architecture manifests in drug compounds with similar physiochemical properties and bioactivity profiles. Preferred synthetic routes to these molecules have remained unchanged since the discovery of “sulfa” drugs early in the 20th century and have several disadvantages. So, how can we better make these molecules? Sulfur fluoride exchange (SuFEx) chemistry is emerging as a promising synthetic tool in chemical biology, bioorganic, and medicinal chemistry. In synthesis, sulfur (VI) fluorides show great promise as building blocks in organic chemistry due to their increased stability compared to other sulfur (VI) halogen analogues. Over the past decade, innovations in synthesizing S(VI) fluorides have unlocked their potential for the development of bench- stable libraries of readily available precursors for derivatization in drug discovery. Key to the adoption of SuFEx chemistry is the development of efficient methods for synthesizing and reacting sulfur(VI) fluorides. This presentation will focus on the Ball group’s contributions to sulfur fluoride chemistry and their medicinal chemistry applications. New SuFEx methods that react a broad set of S(VI) fluorides with carbon, oxygen, and nitrogen-based nucleophiles towards structurally diverse S(VI) compounds will also be featured – unlocking new forms of S(VI) compounds with strong potential for biological activity. The presentation will also highlight the groups’ use of emerging tools in bioorganic, computational chemistry, high- throughput experimentation, and data science to inform the design and understanding of new reactions and the rapid creation of molecular libraries. The presentation will also feature accounts of how undergraduate researchers have led and driven projects with industrial and academic collaborators.

Nicholas Ball

Prof. Nicholas Ball grew up in Chattanooga, TN. He received his B.A. in Chemistry at Macalester College in 2005. He completed his Ph.D. in 2011 under Prof. Melanie Sanford at the University of Michigan, working on C–F and C–CF3 bond formation using high- oxidation-state palladium. In 2010, he headed to the California Institute of Technology to pursue his postdoctoral studies with Prof. David Tirrell as an NIH Postdoctoral Fellow. Prof. Ball started as an ssistant Professor at Amherst College in 2013. In 2015, Prof. Ball joined the faculty at Pomona College and is now an Associate Professor of Chemistry with tenure. His current research focuses on developing new methods to make and use sulfur-based molecules for drug targets, biological chemical probes, and materials science. His lab’s work involves making molecules, machine learning, and computational chemistry. His work features collaborations with industry and internationally, as well as with professors at other predominantly undergraduate institutions. Prof. Ball’s honors and awards include the Henry Dreyfus TeacherScholar Award, 2022 Chemical and Engineering News LGBTQ+ trailblazer, and a two-time Wig Distinguished Professor awardee (2018 and 2024). His research has been funded by NIH, NSF, and the American Chemical Society.

Hosted by Professor Courtney Roberts

Professor Richard Vachet
Department of Chemistry
University of Massachusetts Amherst

Protein Structure, Binding, and Aggregation in Complex Mixtures

Characterizing the higher-order structures (HOS) and interactions of proteins in complex mixtures is challenging and requires the development of new tools. Mass spectrometry (MS)-based techniques are emerging as valuable tools in structural biology, and among these tools covalent labeling (CL) methods have some unique advantages that can be exploited to study protein structure, protein interactions, and protein aggregation, including in live cells. In CL-MS, HOS and binding information are encoded via the formation of covalent bonds that can survive the many steps (i.e. cell lysis, extraction, digestion, separation, MS/MS) needed to analyze proteins by MS. We are developing and applying new CL-MS methods to study the pre-amyloid forms of two important amyloid systems. One is β-2-microglobulin (β2m), which forms amyloids in dialysis-related amyloidosis. The second is Tau, which is important in various tauopathies such as Alzheimer’s disease. We are also developing an approach that can study Tau binding to the low-density lipoprotein receptor-related protein 1 (LRP1) in live cells. In our work on β2m, we have used CL-MS to characterize the initial amyloidogenic change that this protein undergoes and have mapped the energy landscape of this structural change. In addition, we have used CL-MS to determine the structures of pre-amyloid oligomers that have led to the development of small- molecule inhibitors that prevent β2m amyloid formation. Our work on Tau is focused on understanding the transition of this structurally disordered protein into ordered aggregates, and we have also recently been studying its interaction with LRP1, which is a membrane-associated receptor that is a critical determinant for Tau spread and aggregation. To study the ordering of Tau’s structure as it aggregates, we use native MS to monitor its conformational heterogeneity over time. Tau binding to LRP1 relies on CL-MS based mapping of this protein-receptor interaction on live H4i neuroglioma cells. Tau-LRP1 interactions promise to reveal potential approaches for drug intervention for Tau uptake.

Richard Vachet

Richard Vachet is a Professor in the Chemistry Department at the University of Massachusetts Amherst. He received a Ph.D. in Analytical Chemistry from the University of North Carolina- Chapel Hill and did postdoctoral research at the US Naval Research Laboratory from 1997 to 1999 as a National Research Council Postdoctoral Research Associate. He began his independent career at the University of Massachusetts Amherst in 1999. His current research focuses on (a) the development and application of mass spectrometry-based methods to study protein amyloid formation; (b) the development of new tools to study the higher order structure of protein therapeutics; and (c) the detection and imaging of nanomaterial drug delivery agents in biological systems. He has published over 180 peer-reviewed journal articles and has been a member of the Editorial Board of the Journal of the American Society for Mass Spectrometry and the Features Panel for Analytical Chemistry. He has also won several awards, including the Outstanding Research Award from the University of Massachusetts Amherst, the GlaxoSmithKline Lectureship in Analytical Chemistry, and the Young Investigator Award from the American Society for Mass Spectrometry.

Hosted by Professor Varun Gadkari