Latest Publications Garcia Lab PublicationsdELTA-MS: A Mass Spectrometry-Based Proteomics Approach for Identifying ADP-Ribosylation Sites and Forms March 13, 2025ADP-ribosylation, characterized by the addition of adenosine diphosphate ribose, can occur in both monomeric (MARylation) and polymeric (PARylation) forms. Little is known about the specific contributions of MARylation and PARylation to cellular processes due to a lack of tools for jointly investigating these individual forms. We present a novel mass spectrometry (MS)-based proteomics approach that […]Effect of Brief Maternal Exposure to Bisphenol A on the Fetal Female Germline in a Mouse Model March 4, 2025BACKGROUND: Environmental contamination by endocrine disrupting chemicals (EDCs) has created serious public health, ecological, and regulatory concerns. Prenatal exposures can affect a wide range of developing organ systems and are associated with adverse changes to behavior, metabolism, fertility, and disease risk in the adult. The most serious and puzzling observation for some EDC exposures is […]The conserved N-terminal SANT1-binding domain (SBD) of EZH2 Regulates PRC2 Activity February 20, 2025Polycomb group proteins maintain gene expression patterns established during early development, with Polycomb Repressive Complex 2 (PRC2) methyltransferase a key regulator of cell differentiation, identity and plasticity. Consequently, extensive somatic mutations in PRC2, including gain- or loss- of function (GOF or LOF), are observed in human cancers. The regulation of chromatin structure by PRC2 is […]Establishing a Top-Down Proteomics Platform on a Time-of-Flight Instrument with Electron-Activated Dissociation February 17, 2025Top-down proteomics is the study of intact proteins and their post-translational modifications with mass spectrometry. Historically, this field is more challenging than its bottom-up counterpart because the species are much bigger and have a larger number of possible combinations of sequences and modifications; thus, there is a great need for technological development. With improvements in […]Investigation of All Disease-Relevant Lysine Acetylation Sites in α-Synuclein Enabled by Non-canonical Amino Acid Mutagenesis February 3, 2025Aggregates of α-synuclein (αS) are hallmarks of synucleinopathies, including Parkinson's Disease (PD) and Multiple System Atrophy (MSA). We have recently shown that αS lysine acetylation in the soluble monomer pool varies between healthy controls, PD, and MSA patients. To study the effects of lysine acetylation at all disease-relevant sites of αS, we first compared production […]Molecular basis of vitamin-K-driven γ-carboxylation at the membrane interface January 29, 2025The γ-carboxylation of glutamate residues enables Ca^(2+)-mediated membrane assembly of protein complexes that support broad physiological functions, including haemostasis, calcium homeostasis, immune response and endocrine regulation^(1-4). Modulating γ-carboxylation levels provides prevalent treatments for haemorrhagic and thromboembolic diseases⁵. This unique post-translational modification requires vitamin K hydroquinone (KH(2)) to drive highly demanding reactions⁶ catalysed by the...Development of a High-Throughput Platform for Quantitation of Histone Modifications on a New QTOF Instrument December 21, 2024Histone post-translational modifications (PTMs) regulate gene expression patterns through epigenetic mechanisms. The five histone proteins (H1, H2A, H2B, H3, and H4) are extensively modified, with over 75 distinct modification types spanning more than 200 sites. Despite strong advances in mass spectrometry (MS)-based approaches, identification and quantification of modified histone peptides remains challenging because of factors, […]Circular Engineered Sortase for Interrogating Histone H3 in Chromatin November 25, 2024Reversible modification of the histone H3 N-terminal tail is critical in regulating the chromatin structure, gene expression, and cell states, while its dysregulation contributes to disease pathogenesis. Understanding the crosstalk between H3 tail modifications in nucleosomes constitutes a central challenge in epigenetics. Here, we describe an engineered sortase transpeptidase, cW11, that displays highly favorable properties […]Neuropeptides specify and reprogram division of labor in the leafcutter ant <em>Atta cephalotes</em> November 22, 2024Social insects offer powerful models to investigate the mechanistic foundation of elaborate individual behaviors comprising a cooperative community. Workers of the leafcutter ant genus Atta provide an extreme example of behavioral segregation among many phenotypically distinct worker types. We utilize the complex worker system of Atta cephalotes to test the molecular underpinnings of behavioral programming […]Metabolic Control of Glycosylation Forms for Establishing Glycan-Dependent Protein Interaction Networks November 18, 2024Protein-protein interactions (PPIs) provide essential insights into the complex molecular mechanisms and signaling pathways within cells that regulate development and disease-related phenotypes. However, for membrane proteins, the impact of various forms of glycosylation has often been overlooked in PPI studies. In this study, we introduce a novel approach, glycan-dependent affinity purification followed by mass spectrometry […]
