A5061054416- Mass Spectrometry Techniques and Applications
- Analytical Chemistry and Chromatography
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Enzyme Structure and Function
- Protein purification and stability
- RNA and protein synthesis mechanisms
- Inflammasome and immune disorders
- Amyloidosis: Diagnosis, Treatment, Outcomes
- interferon and immune responses
- Glycosylation and Glycoproteins Research
- Metabolomics and Mass Spectrometry Studies
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Erythrocyte Function and Pathophysiology
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Protein Kinase Regulation and GTPase Signaling
- Inorganic and Organometallic Chemistry
- Toxin Mechanisms and Immunotoxins
- Cellular transport and secretion
SignaBlok (United States)
2023
University of Massachusetts Chan Medical School
2018-2023
Broad Institute
2023
University of Massachusetts Amherst
2014-2018
Amherst College
2016
Activated macrophages undergo a metabolic switch to aerobic glycolysis, accumulating Krebs' cycle intermediates that alter transcription of immune response genes. We extended these observations by defining fumarate as an inhibitor pyroptotic cell death. found dimethyl (DMF) delivered cells or endogenous reacts with gasdermin D (GSDMD) at critical cysteine residues form S-(2-succinyl)-cysteine. GSDMD succination prevents its interaction caspases, limiting processing, oligomerization, and...
Characterization of biopharmaceutical products is a challenging task, which needs to be carried out at several different levels (including both primary structure and conformation). An additional difficulty frequently arises due the structural heterogeneity inherent many protein-based therapeutics (e.g., extensive glycosylation or "designer" modifications such as chemical conjugation) introduced postproduction result stress oxidation deamidation). A combination ion-exchange chromatography...
Self-association of proteins is important in a variety processes ranging from acquisition native quaternary structure (where the association tightly controlled and proceeds highly ordered fashion) to aggregation amyloidosis. The latter frequently accompanied (or indeed triggered) by loss structure, but clear understanding complex relationship between conformational changes protein self-association/aggregation remains elusive due great difficulty characterizing these heterogeneous species. In...
Glycosylation is a fundamental modification of proteins and membrane lipids. Toxins that utilize glycans as their receptors have served powerful tools to identify key players in glycosylation processes. Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9–mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 2, which use specific glycolipid, globotriaosylceramide (Gb3), receptors, the plant toxin...
Detailed profiling of both enzymatic (<italic>e.g.</italic>, glycosylation) and non-enzymatic oxidation deamidation) post-translational modifications (PTMs) is frequently required for the quality assessment protein-based drugs.
Seasonal “common-cold” human coronaviruses are widely spread throughout the world and mainly associated with mild upper respiratory tract infections. The emergence of highly pathogenic MERS-CoV, SARS-CoV, most recently SARS-CoV-2 has prompted increased attention to coronavirus biology immunopathology, but T-cell response seasonal remains largely uncharacterized. Here we report repertoire viral peptides that naturally processed presented upon infection a model cell line OC43. We identified...
Significance Orthologous proteins from the three superkingdoms have conserved their structures and functions over evolutionary time. We ask whether folding mechanisms of partially folded states are similarly conserved, using bacterial archaeal representatives IGPS TIM barrel enzyme. Comparison circular dichroism fluorescence spectroscopic studies reveal a highly mechanism, hydrogen–deuterium exchange mass spectrometry analyses highlight similar cores stability in regions dominated by...
Abstract Seasonal “common-cold” human coronaviruses are widely spread throughout the world and mainly associated with mild upper respiratory tract infections. The emergence of highly pathogenic MERS-CoV, SARS-CoV, most recently SARS-CoV-2 has prompted increased attention to coronavirus biology immunopathology, but identification characterization T cell response seasonal remain largely uncharacterized. Here we report repertoire viral peptides that naturally processed presented upon infection...
Abstract Major histocompatibility (MHC) bound viral peptides are the immune signatures to initiate selective and cross-reactive T cell responses. Identifying antigenic targets of adaptive immunity SARS-CoV-2 is a key towards understanding pathogenesis Sars-CoV-2 rapidly evolving mutants. We isolated immunopeptidomes identify naturally processed presented MHC-II (HLA-DR, HLA-DP) MHC-I (HLA-ABC) canonical out-of-frame peptides. identified 5 HLA-DR epitopes (13 peptides) from spike protein, 2...
Background The amyloidogenic transthyretin (TTR) variant, V122I, occurs in 4% of the African American population and frequently presents as a restricted cardiomyopathy. While heterozygosity for TTR V122I predominates, several compound heterozygous cases have been previously described. Herein, we detail features ATTRv amyloidosis associated with novel mutation, T60I/V122I provide evidence supporting amyloidogenecity T60I.Methods A 63-year-old female presented atrial fibrillation, congestive...
Abstract Large-scale cancer sequencing efforts coupled with deep functional genomic interrogation of models provides us an increasingly detailed view the critical drivers required for persistent growth and survival cells. Targeting such has provided significant therapeutic benefit to patients across a wide range cancers, yet progress been, in large part, confined targeting catalytic domains kinases. To expand reach therapeutics into new classes targets, we need identify validate specific...
Abstract Understanding the targets of adaptive immunity to SARS-CoV-2 is essential for vaccine development and interpretation coronavirus disease 2019 (COVID-19) pathogenesis. other human coronaviruses share substantial sequence homology raising possibility that previous exposure seasonal “common cold” could impact T cell response upon infection. Detailed investigation antigenic peptides presented in common infections would be beneficial understand preexisting mediated on The repertoire...