Past Events

2024

  • Apr 19, 2024 - 3:20 PM
    to , -
    Location
    1352 Gilman

    Boone M. Prentice, Ph.D.

    Assistant Professor

    University of Florida

    Hosted by: Young-Jin Lee

    Abstract

    Imaging with high chemical and spatial resolutions using mass spectrometry

    Imaging mass spectrometry is a powerful analytical technique for analyzing the spatial lipidome. This technology enables the visualization of molecular pathology directly in tissues by combining the specificity of mass spectrometry with the spatial fidelity of microscopic imaging. This label-free methodology has proven exceptionally useful in research areas such as cancer diagnosis, diabetes, and infectious disease. However, state-of-the-art experiments stress the limits of current analytical technologies, necessitating improvements in molecular specificity and sensitivity in order to answer increasingly complicated biological and clinical hypotheses. Especially when studying lipids, many isobaric (i.e., same nominal mass) and isomeric (i.e., same exact mass) compounds exist that complicate spectral analysis, with each structure having a potentially unique cellular function. The Prentice Lab develops instrumentation and novel gas-phase reactions to provide unparalleled levels of chemical resolution. These gas-phase transformations are fast, efficient, and specific, making them ideally suited for implementation into imaging mass spectrometry workflows. For example, these workflows have enabled the identification of multiple sn-positional phosphatidylcholine isomers, the separation of isobaric phosphatidylserines and sulfatides, and the identification of fatty acid double bond isomers using a variety of charge transfer and covalent ion/ion reactions as well as ion/electron and ion/photon reactions. Working with biologists and clinicians, we then leverage these novel imaging technologies to understand the molecular events associated with important problems in human health, including infectious disease, diabetes, and neurodegenerative diseases.

    Bio

    Boone Prentice is Assistant Professor in the Department of Chemistry at the University of Florida. He received his B.S. in Chemistry from Longwood University (Farmville, VA), and completed his Ph.D. in Chemistry at Purdue University (West Lafayette, IN) under the mentorship of Prof. Scott McLuckey studying gas-phase ion/ion reactions and ion trap instrumentation. He then completed his postdoctoral work in the Department of Biochemistry at Vanderbilt University (Nashville, TN) as an NIH NRSA fellow under the guidance of Prof. Richard Caprioli before joining the faculty at UF in 2018. He was awarded an NIH Focused Technology Research and Development R01 grant in 2020 and a JDRF Innovation Award in 2023 to support his research developing gas-phase reactions and imaging mass spectrometry technologies to study the molecular pathology of diabetes, infectious disease, neurodegeneration, and neuropharmacology. He was also awarded the 2022 Young Investigator Award from Eli Lilly and Company, which is an unsolicited award given annually by Eli Lilly’s Analytical Chemistry Academic Contacts Committee to recognize a “rising star” in analytical chemistry, and was highlighted as a 2023 Emerging Investigator by the Journal of the American Society for Mass Spectrometry and as a 2023 Young Investigator in (Bio-)Analytical Chemistry by Analytical and Bioanalytical Chemistry.

  • Apr 19, 2024 - 1:10 PM
    to , -
    Location
    1352 Gilman

    Professor Jason Chen

    Scripps Research - Former ISU Professor (2011-2016)

    Hosted by: Wenyu Huang, Levi Stanley and Brett VanVeller

    Abstract:

    Beyond the Round Bottom: Transforming Academic Synthesis

    The Automated Synthesis Facility at Scripps Research provides hardware, software, and services in
    support of data-rich synthetic organic chemistry. Founded in 2017, the facility operates $7 million in
    equipment in support of diverse projects including reaction discovery, kinetics studies, and natural
    products total synthesis. The facility helps scientists to speed up research and improve data quality with
    the long-term goal of enabling innovative projects and transforming organic synthesis research. Towards
    these ends, the facility staff works with Scripps chemists to develop project-specific solutions and with
    instrument vendors to deliver enabling technologies. Vignettes illustrating how the facility works towards
    these goals will include examples from chiral reaction development, DNA-encoded library research,
    isotopic labeling studies, and chemistry involving gaseous reagents.

    Bio:

    Dr. Chen participated in International Chemistry Olympiad in high school, 2nd place in 1997. He
    received his undergrad and master’s at Harvard with Matthew Shair. Dr. Chen then worked two
    years at Enanta Pharmaceuticals as a medicinal chemist working on analogs of the
    immunosuppressant cyclosporin A, mostly by olefin metathesis. He then obtained his Ph.D. from
    The Scripps Research Institute with K.C. Nicolaou including postdoctoral studies, with work
    including total synthesis of uncialamycin (route used by BMS in antibody-drug conjugate
    program), asymmetric dichlorination, and co-authorship of the book Classics in Total Synthesis
    III. Dr. Chen then went to Iowa State University as an Assistant Professor working on reaction
    development, total synthesis, and biorenewable materials research, where he received an NSF
    CAREER and an ISU honors program teaching award. Dr. Chen then returned to Scripps
    Research where he built the Automated Synthesis Facility from scratch and obtained an NIH S10
    equipment grant. He is now the Senior Director overseeing the collective core facilities at
    Scripps Research.

  • Head shot of speaker
    Apr 12, 2024 - 3:20 PM
    to , -
    Location
    1352 Gilman

    Professor George Lisi, Brown University, BioPhysical

    Macrophage migration inhibitory factor (MIF) is a multifunctional immunoregulatory protein that is a key player in the innate immune response. Despite its symmetric trimer structure composed of small, identical protein subunits, MIF contains three enzymatic active sites, a pro-inflammatory receptor binding site, and is implicated in more than 30 protein-protein interactions and diseases.  MIF is implicated in nearly all inflammatory diseases and several cancers, though the mechanism by which MIF engages in promiscuous interactions with substrates and partner proteins is unclear at the biophysical level, hampering the visualization and targeting of MIF disease states. This talk will describe the structural and dynamic factors that facilitate multi-domain crosstalk and control multiple biological activities in MIF and its homologs. Primarily using solution NMR, the highly dynamic MIF structure will be connected to rearrangements that tune its specific catalytic and pro-inflammatory functions.

    A secondary focus will be on efforts to leverage biochemical stimuli such as redox conditions and mutations to understand altered MIF structures and signatures of its “disease states.” NMR spectroscopy will reveal real-time, redox-dependent alterations to the MIF solution structure, and through mass spectrometry, detect residue-level modifications that acts as “molecular switches” for selective binding. Biophysical studies implicate redox-dependent structural dynamics as a means to toggle the MIF functions, and these motions are leveraged in the discovery of latent allosteric sites through mutational analysis. A disruption of redox-dependent structural triggers within MIF attenuate its pro-inflammatory CD74 receptor activation in vivo, suggesting sites of redox sensitivity can be targets for structure-based drug design aimed at modulating MIF its pathological function.

  • Head shot of speaker
    Apr 12, 2024 - 1:10 PM
    to , -
    Location
    1352 Gilman

    Professor Severin T. Schneebeli, Purdue University

    Peptide drugs represent a rapidly growing segment of the pharmaceutical market. Like antibody drugs, peptides can target key protein-protein interactions, which is difficult to accomplish with small-molecule drugs. Additional key advantages of peptide drugs include their modular synthesis, their metabolism into generally non-toxic amino acids, their relatively low immunogenicity, and the ability to readily prepare libraries. Yet, major challenges remain with peptide drugs that are mostly related to their proteolytic stability and reduced ability to cross cellular membranes. These major ADME-related challenges have not only made it difficult for peptide drugs to reach intracellular targets but have also limited desirable oral formulations of peptide drugs. To meet these challenges, research in the Schneebeli lab is focused on discovering new high-throughput selection approaches for identifying optimal peptide sequences that are not only able to selectively bind their therapeutic targets but also display more favorable ADME properties. To reach this goal, we make use of new sequencing tools driven by supramolecular chemistry advances in our laboratory. This seminar will provide an overview of our new supramolecular tools with a highlight on how to synthetically access them, while also providing a road map outlining their applications for next-generation sequencing of pharmaceutical peptide/protein libraries.

  • Head shot of speaker
    Apr 5, 2024 - 3:20 PM
    to , -
    Location
    1352 Gilman

    Professor Cong Liu, Argonne National Laboratory, Physical/Inorganic

    Single-site heterogeneous catalysts (e.g., single-atom catalysts, supported organometallics and metal hydrides, etc.) have gained increasing attention in both industry and academia, integrating crucial aspects of homogeneous catalysis (high activity and selectivity) with the stability of heterogeneous catalysts. Because high-surface-area supports are usually preferred in synthesizing these catalysts, a lot of these catalysts often present high heterogeneity in the catalytic sites, resulting in a distribution of active-site structures and site-specific activities. Meanwhile, some of these catalysts may not be stable under reaction condition and can experience dynamic evolution during catalysis. In situ spectroscopic characterization (e.g., X-ray absorption spectroscopy (XAS)) is an effective technique to characterize supported catalysts under reaction conditions. In XAS, X-ray Absorption Near Edge Spectroscopy (XANES) spectra contains key information on the local coordination environment of the metal atom(s), and thus the analysis of which is more challenging. Some key characteristics of the metal centers and their coordination environment can be directly extracted from the experimental XAS, such as average oxidation state and coordination number. However, certain bonding interactions that are key to catalysis, such as metal-hydride, often present only subtle features in XANES spectra, and these are challenging to interpret directly from experimental spectra. In addition, interpreting XANES spectra of supported catalysts with high site heterogeneity is particularly difficult. This is because XAS measures all the catalytic sites, and the response from this technique is dominated by the sites with the highest volumetric density. However, the overall activity is dominated by the sites with the highest turnover frequencies, not necessarily those with the highest density. Computational XANES simulations offer a powerful technique for interpreting experimental spectra, providing a one-to-one correspondence between the molecular structure and spectral features. In this talk, we will discuss about our recent work on a supported organovanadium catalyst and a supported single-atom Cu catalyst to demonstrate that when integrated in situ and computational XANES analyses are combined with systematic mechanistic simulations, the most active catalytic site in dynamic and disordered catalytic systems can be identified. 

  • Head shot of speaker
    Apr 5, 2024 - 1:10 PM
    to , -
    Location
    1352 Gilman

    Professor Andrew G. Roberts, University of Utah

    Peptide cyclization methods are useful in the development of therapeutic peptide leads with improved metabolic stability properties. To develop residue-selective peptide cyclization strategies, we draw inspiration from cyclic and lassoed peptide natural product scaffolds that exhibit diverse biological activities. For example, the reactive phenolic linkages found in both the arylomycin and vancomycin families of antibacterial natural products motivated us to develop simple-to-perform oxidative methods that generate electrophilic 1,2,4-triazoline-3,5-dione moieties on native peptides to ultimately achieve residue-selective cyclizations (Keyes et al. J. Am. Chem. Soc. 2023, 145, 10071). In awe of lasso peptides, non-covalently interlocked and proteolytically-stable bioactive natural products, we are working in collaboration with the Swanson laboratory to develop and understand strategies for reversible isopeptide bond formation that could enable the sequence-independent chemical synthesis of lasso peptides. Detailed accounts of these developments and their applications will be presented.

  • Shinae Kim
    Mar 28, 2024 - 2:30 PM
    to , -
    Location
    1352 Gilman

    Exploring decomposition mechanism of Hydroxylamine on Cu(111) and Iridium(111) surface using Pynta – Workflow code for heterogeneous catalysis reaction

     

RSS Feed