Past Seminars & Events

Professor Marcey Waters
Department of Chemistry
The University of North Carolina at Chapel Hill

New Strategies to Target “Undruggable” Histone Reader Proteins

Histone trimethyllysine (Kme3) reader proteins translate lysine methylation into changes in gene expression, making them important targets for understanding and treating cancer and other diseases. However, selective inhibition remains challenging because multiple reader proteins can recognize the same Kme3 site, often through conserved aromatic cages. Our studies address this gap by defining the physical and structural principles governing Kme3 recognition and identifying the differences in the aromatic cages and binding interfaces that can be exploited for selective inhibition. With mechanistic insights, we are developing and and evaluating a novel set of Kme3 mimics with improved affinity, selectivity, and cell permeability. Together, these findings highlight trimethyllysine mimics as a promising strategy for achieving selective inhibition of challenging epigenetic reader proteins.

Marcey Waters

Prof. Marcey Waters is the Glen H. Elder, Jr., Distinguished Professor of Chemistry at the University of North Carolina Chapel Hill. She completed a bachelor’s degree in chemistry at UC San Diego in. Dr. Waters earned a Ph.D. in chemistry from the University Chicago in the group of Bill Wulff in 1997. She pursued research as an NIH postdoctoral fellow with Dr. Ronald Breslow at Columbia University before joining the faculty of UNC Chapel Hill in 1999. She was promoted to full professor in 2009. Her current research program focuses on the study of protein-protein interactions mediated by epigenetic post-translational modifications and chemical sensors for “forever” chemicals. Dr. Waters is a fellow of the AAAS and served as the President of the American Peptide Society (APS) from 2017-2019. Her research accomplishments have been recognized most recently with the Vincent du Vigneaud Award from the APS in 2023.

Hosted by Professor William Pomerantz

Professor Jeffrey Lipshultz
Department of Chemistry
Stony Brook University

Designing, Understanding, and Manipulating Radical Reaction Pathways Driven by Light

Efforts in the Lipshultz Group are largely geared towards developing versatile platforms for synthetic transformations, leveraging radical reaction pathways driven by light. Among these platforms are (i) titanium ligand-to-metal charge-transfer (LMCT) photocatalysis, (ii) Vit B6-inspired Photo-Decarboxylase catalysis, and (iii) Vit B6-dependent aminomutase-inspired amino acid homologation. Each of these reaction classes leverages unique photochemical and/or radical key steps which provide opportunity for manipulation and control through fundamental understanding. First, electronic tuning of photoactive titanium catalysts allows for rational manipulation of photochemistry, manifesting in controlled photocatalysis for C–C and C–H bond functionalization. Tuning of the redox properties can further enable reversible C–C bond activation for formal alcohol metathesis. Second, taking inspiration from Dunathan’s stereoelectronic hypothesis for Vit B6-dependent enzymatic reactivity, Photo-Decarboxylase catalysis is realized through catalyst- templated hyperconjugative charge-transfer, delivering access to decarboxylated diradical species which engage in regiospecific bond construction. Finally, α-to-β amino acid homologative transmutation can be achieved through a highly polarized biomimetic 3-exo-trig radical cascade. Fundamental mechanistic studies, combined with density functional theory calculations, deliver deeper understanding of each mechanistic paradigm and provide prospects for further development.

Jeffrey Lipshultz

Jeff was born in New York City and raised in North Jersey. In 2013, he received an A.B. in Chemistry from Harvard College, where he worked in the lab of Prof. Andrew Myers. Jeff returned to New Jersey to pursue graduate studies with Prof. David MacMillan at Princeton University, where he worked on reaction development using metallaphotoredox catalysis and total synthesis of oligomeric polypyrroloindoline natural products. After receiving his Ph.D. in 2018, Jeff conducted postdoctoral studies as a Dreyfus Foundation Environmental Chemistry Fellow with Prof. Alexander Radosevich at MIT, developing new reaction methods employing organophosphorus catalysis. Jeff began his independent career in the Department of Chemistry at Stony Brook University as an Assistant Professor in Summer 2022. At Stony Brook, research in the Lipshultz Group focuses on the development and study of new photochemical and radical methods, especially leveraging photo- excitation of rationally-designed catalyst-substrate complexes. Ongoing work has been supported by an ACS Green Chemistry Institute Pharmaceutical Roundtable Ignition Grant, ACS Petroleum Research Fund Doctoral New Investigator Award, NIH NIGMS Maximizing Investigators’ Research Award (MIRA), NSF Faculty Early Career Development Award (CAREER), Stony Brook Research and Innovation Seed Grant, and Stony Brook Trustees Faculty Award, as well as a broad collaboration with Merck.

Hosted by Professor Ian Tonks

Professor Jodi Hadden-Perilla
Chemistry and Biochemistry Department
University of Delaware

Icosahedral virus capsids through the computational microscope

At the technological interface of chemistry, physics, biology, and computing, there exists the only scientific instrument capable of characterizing the conformational dynamics of macromolecules, and the functional properties they give rise to, at atomistic resolution. The computational microscope, realized through the application of supercomputers to perform all-atom molecular dynamics simulations, has emerged as a powerful tool to investigate the complex cellular machinery that supports life, as well as the pathogenic systems that threaten it. The Hadden Lab at University of Delaware uses the computational microscope to study biological machines, particularly the capsids of icosahedral viruses. Professor Hadden-Perilla will discuss her group’s progress toward elucidating the mechanisms by which the hepatitis B virus (HBV) capsid carries out its functions during infection. Notably, the computational microscope has enabled discovery of new conformations, never isolated by experimental methods, that provide key insights into the capsid’s regulatory role in assembly, pre-genome packaging, and intracellular trafficking.

Jodi Hadden-Perilla

Professor Jodi Hadden-Perilla uses multimillion- atom molecular dynamics simulations to study the functional motions of viruses. In a broader context, her work is also applicable to the study of protein cages and virus-like particles. Professor Hadden- Perilla joined the faculty in the Department of Chemistry and Biochemistry at UD in 2019, was promoted to Associate Professor with tenure in 2025, and now holds the C. Eugene Bennet Early Career Chair of Chemistry. She obtained her PhD in computational chemistry at the University of Georgia with Professor Robert Woods. She was a postdoctoral researcher with Professor Klaus Schulten at the University of Illinois at Urbana- Champaign and was an independent postdoctoral researcher at the UD for two years before becoming faculty. In addition to her principal appointment, Professor Hadden-Perilla is an affiliated faculty member with the Data Science Institute and the Center for Bioinformatics and Computational Biology at UD.

Hosted by Ethan Clare

Professor Bess Vlaisavljevich
Department of Chemistry
University of Iowa

High-Valent f-element Coordination Complexes: Connecting Quantum Chemical Modelling to Measured Properties

The electronic structure of the coordination chemistry of the 4f-elements typically involves metal-centered valence orbitals and weak ligand fields. However, stabilizing unusually high formal oxidation states requires designing ligands that fall outside this classical paradigm. This talk explores how a combined use of density functional theory (DFT) and multiconfigurational methods can be used to understand recently synthesized high-valent praseodymium complexes. By characterizing the pseudo-tetrahedral [Pr(IV)(NPtBu3)3] complex, we examine the interplay between crystal field splitting and spin-orbit coupling. Comparisons between this complex and its isoelectronic Ce(III) analogue are attributed to differences in crystal field splitting, based on EPR measurements and theory. Moreover, this complex has an accessible Pr5+/4+ redox couple allowing it to be oxidized to form a molecular praseodymium complex in the formal +5 oxidation state, specifically [Pr(V)(NPtBu3)3]+. The complex has a multiconfigurational singlet ground state resulting from an inverted ligand field. To place the electronic structure of the 4f species in context, this talk will draw parallels to the inverted ligand fields observed in high-valent transition metal chemistry, specifically in Cu(II) species. The comparison between the 4f and 3d metals will lead into a conversation about the high- valent actinides. Specifically, the dramatic change in molecular geometry observed for a uranium(V) oxo complex. By invoking the concept of an “inverse trans influence”, we can understand the different behavior with soft-donor sulfur groups compared to the analogous oxo-donating ligands. This final section of the talk will focus on how experimental observables like structure and spectra cannot always be used alone to assign bonding but provide important metrics that, only when computed, can be used to provide the full picture of what stabilizes the structure.

Bess Vlaisavljevic

Bess Vlaisavljevich is from St. Paul, Minnesota. She received her B.A. in chemistry from the University of Minnesota Morris in 2007. She then received her M.S. and Ph.D. degrees working with Prof. Laura Gagliardi from the Department of Chemistry at the University of Minnesota Twin Cities in 2010 and 2013, respectively. Her PhD work focused on studying the electronic structure of the f-elements with multiconfigurational methods. Following this, she worked as a postdoctoral scholar at the University of California Berkeley with Prof. Berend Smit using molecular simulation and density functional theory to study gas separations and adsorption in nanoporous materials. Later, at Northwestern University with Prof. Toru Shiozaki, she was involved in developing the (X)MS-CASPT2 analytical gradient code in the program package BAGEL. In 2017, she began her independent career at the University of South Dakota. Her research focuses on using multireference quantum chemistry theories for a variety of problems in transition metal and actinide chemistry. She was recently awarded a Department of Energy Early Career Awards and USD’s Early/Mid- Career President’s research award for her efforts. In 2023, she was awarded tenure and promoted to Associate Professor. In 2024, she moved to the University of Iowa as an Associate Professor.

Hosted by Professor Anthony Schlimgen

Professor Evan Williams
Department of Chemistry
University of California, Berkeley

Overcoming Molecular Complexity One Ion at a Time

Heterogeneous materials can be challenging to analyze especially when the masses of individual components extend beyond 100 kDa. With mass spectrometry, individual charge states produced by electrospray ionization can be difficult to resolve due to overlaps in m/z from other components or from adduction of salts or other non-specific molecular interactions. One demonstrated solution to this problem of sample heterogeneity for high mass analytes is to measure the charge as well of the m/z of individual ions so that the mass of each ion can be determined without interference from other ions. Single ion mass measurements have been performed with a variety of instrument types, but charge detection mass spectrometry with electrostatic ion traps have the advantage of virtually unlimited mass range, single charge accuracy, and the ability to make dynamic measurements. A primary challenge is to acquire single ion data sufficiently rapidly to make this method practical. Solutions to this challenge, as well as state of the art capabilities of charge detection mass spectrometry and applications to viral and nanoparticle analysis will be discussed. Results from experiments aimed at understanding the chemistry and physics of charged droplets, structures and reactivities of viruses, and applications in nanoparticle characterization will also be presented.

Evan Williams

Evan Williams is a Distinguished Professor of Chemistry and Biophysics at the University of California at Berkeley and the Faculty Director of the QB3/Chemistry Mass Spectrometry Center. He also holds a joint appointment in Molecular Biophysics & Integrated Bioimaging at the Lawrence Berkeley National Laboratory. His research aims to develop novel instrumental and computational techniques in mass spectrometry, separations, chemical imaging and laser spectroscopy for improved molecular structure elucidation and apply these methods to interesting chemical problems of both practical and fundamental interest.

Hosted by Professor Varun Gadkari

Professor Vicki Wysocki
School of Chemistry & Biochemistry
Georgia Institute of Technology

Native Mass Spectrometry, Mass Photometry, and CryoEM of Nucleoprotein Complexes

Tools to address structural biology problems continue to improve. Native mass spectrometry (nMS) and associated technologies such as ion mobility are becoming an increasingly important component of the structural biology toolbox. When the mass spectrometry approach is used early or mid-course in a structural characterization project, it can provide answers quickly using small sample amounts and samples that are not fully purified. Integrating sample preparation/purification with effective dissociation methods (e.g., surface-induced dissociation, SID), ion mobility, and computational approaches provides an MS workflow that can enable biochemical, synthetic biology, and systems biology approaches. Native MS can determine whether the complex of interest exists in a single or in multiple oligomeric states and can provide characterization of topology/ intersubunit connectivity, and other structural features. Beyond its strengths as a stand-alone tool, nMS can also guide and/or be integrated with other structural biology approaches such as SEC, SAXS, mass photometry, X-ray crystallography, and cryoEM. Examples for protein and nucleoprotein complexes will be presented to illustrate complementary data provided by native MS/ SID and other structural biology tools. 

References 

[1] Snyder, Harvey, Wysocki, V. H., Chemical Reviews, 2022, 122, 8, 7442–7487. 

[2] Karch, Snyder, Harvey, Wysocki Annu. Rev. Biophys. 2022. 51, 157–79.

Vicki Wysocki

Vicki Wysocki is Chair of the School of Chemistry and Biochemistry at Georgia Institute of Technology and an internationally recognized leader in mass spectrometry and structural biology. She earned her BS in Chemistry from Western Kentucky University and her PhD in Chemistry from Purdue University, followed by postdoctoral work at Purdue and the Naval Research Laboratory. Her academic career has included faculty positions at Virginia Commonwealth University, the University of Arizona, and The Ohio State University, where she was an Ohio Eminent Scholar and Director of the Campus Chemical Instrument Center. She has held major leadership roles in the American Society for Mass Spectrometry and The Protein Society, served in senior editorial positions for leading journals, and received major honors including the Thomson Medal, the ACS Field and Franklin Award, the ACS Analytical Division Chemical Instrumentation Award, and the ASMS Distinguished Contribution Award.

Hosted by Professor Varun Gadkari

Professor Vicki Wysocki
School of Chemistry & Biochemistry
Georgia Institute of Technology

Surface Collisions Across a Career: From Peptides to Virus-like Particles

Hyperthermal ion–surface collisions for characterizing projectile ions by tandem mass spectrometry (MS/MS) were introduced by the Cooks laboratory at Purdue University in the 1980s. Early on, it became clear that surfaces, which are far more massive collision targets than the neutral gas used in collision-induced dissociation (CID), could be valuable for dissociating massive ions. Unfortunately, instruments of the day could not ionize and transmit ions with high mass- to-charge ratios (m/z). In the early years, the Wysocki laboratory used surface collisions to help develop the mobile proton model for peptide fragmentation. More recently, we have extended these studies to characterize protein and nucleoprotein complexes. As methods and instruments have evolved to accommodate more massive ions, surface-induced dissociation (SID) has been integrated into several instrument platforms, including QqQ, QTOF, FT-ICR, and Orbitrap systems, and coupled with online separations, ion mobility, and other activation methods, including electron- based dissociation (ExD). SID measurements can inform multiple stages of biochemical and structural biology projects by revealing features such as subunit connectivity, topology, interfaces, and assembly organization that complement information from other structural biology tools. Examples will illustrate the development of native mass spectrometry experiments for structural characterization, including native “complex down” structural proteomics of lysates, combining size exclusion chromatograpy, capillary zone electrophoresis, and surface induced dissociation

Vicki Wysocki

Vicki Wysocki is Chair of the School of Chemistry and Biochemistry at Georgia Institute of Technology and an internationally recognized leader in mass spectrometry and structural biology. She earned her BS in Chemistry from Western Kentucky University and her PhD in Chemistry from Purdue University, followed by postdoctoral work at Purdue and the Naval Research Laboratory. Her academic career has included faculty positions at Virginia Commonwealth University, the University of Arizona, and The Ohio State University, where she was an Ohio Eminent Scholar and Director of the Campus Chemical Instrument Center. She has held major leadership roles in the American Society for Mass Spectrometry and The Protein Society, served in senior editorial positions for leading journals, and received major honors including the Thomson Medal, the ACS Field and Franklin Award, the ACS Analytical Division Chemical Instrumentation Award, and the ASMS Distinguished Contribution Award. 

Hosted by Professor Varun Gadkari

Professor Vicki Wysocki
School of Chemistry & Biochemistry
Georgia Institute of Technology

Native Mass Spectrometry of Protein Complexes

Characterization of the overall topology and inter-subunit contacts of protein complexes, and their assembly/ disassembly and unfolding pathways, is critical because protein complexes regulate key biological processes, including processes important in understanding and controlling disease. Tools to address structural biology problems continue to improve. Native mass spectrometry (nMS) and associated technologies such as ion mobility and variable temperature electrospray ionization are becoming increasingly important components of the structural biology toolbox. When the native mass spectrometry approach is used early or mid-course in a structural characterization project, it can provides answers quickly for small amounts of sample, even when heterogeneity is present. Integration of sample preparation/ purification with effective dissociation methods (e.g., surface-induced dissociation, SID), ion mobility, and computational approaches provide a workflow that is enabling in biochemical, synthetic biology, and systems biology approaches. Native MS can determine whether a complex of interest exists in a single or multiple oligomeric states, and surface-induced dissociation can characterize topology/inter-subunit connectivity and other structural features. Examples will illustrate the coupling of surface collisions to electron capture charge reduction and charge detection mass spectrometry for the characterization of protein complexes, including enzymes, protac-bound complexes, and adeno- associated virus capsids. 

References 

[1] Snyder, Harvey, Wysocki, V. H., Chemical Reviews, 2022, 122, 8, 7442–7487. 

[2] Karch, Snyder, Harvey, Wysocki Annu. Rev. Biophys. 2022. 51, 157–79.

Vicki Wysocki

Vicki Wysocki is Chair of the School of Chemistry and Biochemistry at Georgia Institute of Technology and an internationally recognized leader in mass spectrometry and structural biology. She earned her BS in Chemistry from Western Kentucky University and her PhD in Chemistry from Purdue University, followed by postdoctoral work at Purdue and the Naval Research Laboratory. Her academic career has included faculty positions at Virginia Commonwealth University, the University of Arizona, and The Ohio State University, where she was an Ohio Eminent Scholar and Director of the Campus Chemical Instrument Center. She has held major leadership roles in the American Society for Mass Spectrometry and The Protein Society, served in senior editorial positions for leading journals, and received major honors including the Thomson Medal, the ACS Field and Franklin Award, the ACS Analytical Division Chemical Instrumentation Award, and the ASMS Distinguished Contribution Award. 

Hosted by Professor Varun Gadkari

Professor Zhen-Gang Wang
Department of Chemical Engineering
California Institute of Technology

Self-Assembly of End-Charged Block Copolymers and Blends: Effects of Ion Clustering

Introducing a small number of ionic groups at polymer chain ends — whether within a single diblock copolymer or across two different homopolymers in a blend — has emerged as a promising strategy for directing self-assembly, with applications ranging from compatibilizing immiscible polymer blends to templating functional and ion-conducting nanostructures. We study the effects of these end charges on the self-assembly of diblock copolymers and binary polymer blends using a self-consistent field theory that incorporates strong ion correlations. Under the low-dielectric conditions typical of polymer melts, the charged ends aggregate into multi-ion clusters, which reshapes the self- assembly of both systems. In the case of end-charged diblock copolymers, the resulting clusters act as compact, curvature- favoring foci around which the chains radiate, unlocking complex network morphologies, such as the single primitive and single gyroid phases, that are normally inaccessible to neutral melts. In binary blends with oppositely charged termini, the electrostatic attraction between chain ends suppresses the macroscopic phase separation in the corresponding uncharged blend and results in microphase separation instead. Interestingly, the resulting phase diagram is simpler — dominated by lamellar and cylindrical phases — than expected based on the pairwise-bonded effective diblock picture previously invoked to describe these systems. We attribute this difference to the difference in the location of the ion clusters in the two systems: in the diblock they act as compact foci to organize the chains around them, while in the blend they are confined to the interface separating the two species, where they resist curvature rather than favor it. Finally, for both systems, ordered microphase structures can appear at segregation strengths significantly lower than that required for the corresponding uncharged diblock copolymers.

Zhen-Gang Wang

Zhen-Gang Wang received his B.Sc. in Chemistry in 1982 from Beijing (Peking) University, and his Ph.D. in Chemistry in 1987 from the University of Chicago. He did postdoctoral research first in Exxon Research and Engineering Company and then at UCLA. Since 1991 he has been on the Chemical Engineering faculty at the California Institute of Technology, where he is currently the Dick and Barbara Dickinson Professor. He has also served as Executive Officer (department chair) for Chemical Engineering for 6 years. 

Wang’s research is the theoretical and computational study of structure, phase behavior, interfacial properties and dynamics of polymers, soft materials, and biophysical systems. His current activities revolve around three main themes: charged systems, including polyelectrolytes, salt-doped polymers, and electric double layers; nucleation or more generally barrier crossing in polymers and soft matter; and nonlinear rheology of polymer gels and entangled polymers. 

Wang is a fellow of the American Physical Society and a member of the U. S. National Academy of Engineering. He is recipient of several significant awards and honors, including the Camille Dreyfus Teacher–Scholar Award (1995), the Alfred P. Sloan Award (1996), the Braskem Award from the American Institute of Chemical Engineers (AIChE) (2018), the AIChE Alpha Chi Sigma Award (2023), and the American Physical Society Polymer Physics Prize (2024). In addition, he was awarded the Richard P. Feynman Prize for Excellence in Teaching (2008), Caltech’s highest teaching honor. 

Wang has served on the editorial advisory boards of Journal of Theoretical and Computational Chemistry, Macromolecules, ACS Macro Letters, Giant, Acta Physicochimica Sinica, and Science in China B (Chemistry). He is currently an associate editor for the ACS Journal Macromolecules.

Hosted by Professor Timothy Lodge

Sean Ross, Ph.D.
Senior Scientist II
AbbVie

Enabling chemistry at the interface of late discovery and early development

At AbbVie, the process chemistry group works in collaboration with our discovery and product development science and technology groups to develop active pharmaceutical ingredients (API) from their discovery to market. Critical early deliveries of API to enable preclinical studies requires the development of enabling routes to accelerate drug development. This talk will describe the rapid development of an enabling route to a preclinical target across discovery and process chemistry. The focus of the talk will include the development of a cross electrophile coupling approach to install a key C-C bond, as well as the development of a C-O cross coupling to form the penultimate intermediate This collaborative effort successfully delivered API that was supported a wide range of pre-clinical studies.

Sean Ross

Sean began his formal chemistry education at the University of Nevada, Reno where he obtained his B.S. in chemistry. During this time, he performed undergraduate research with Professor Bob Sheridan on the matrix isolation of carbenes, and with Professor Mazal on the synthesis of 1.1.1 propellanes. This later led him to pursue a Ph.D. in organic chemistry from the University of Minnesota. At the University of Minnesota, Sean joined the lab of Professor Tom Hoye working on the development of methodologies utilizing thermally generated benzynes. After defending his Ph.D. in 2011, Dr. Ross moved to the University of Utah where he joined the group of Professor Matt Sigman. There he worked on applying data science techniques to the redox-relay Heck reaction. In 2021, Sean joined AbbVie as a part of the Process Chemistry team. His current work is focused on the development of enabling chemistry to facilitate the kilo-scale manufacture of active pharmaceutical ingredients for late preclinical and early clinical studies.

Hosted by Professor Christopher Douglas
Sponsored by AbbVie