A5064010832- Virus-based gene therapy research
- CAR-T cell therapy research
- Cancer Research and Treatments
- CRISPR and Genetic Engineering
- Connexins and lens biology
- Animal Genetics and Reproduction
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Pluripotent Stem Cells Research
- NF-κB Signaling Pathways
- Molecular Biology Techniques and Applications
- Protein Degradation and Inhibitors
- Sperm and Testicular Function
- Renal and related cancers
- Reproductive Biology and Fertility
- Genomics and Chromatin Dynamics
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Retinal Development and Disorders
- Retinoids in leukemia and cellular processes
- interferon and immune responses
- Reproductive Physiology in Livestock
- Single-cell and spatial transcriptomics
- Kawasaki Disease and Coronary Complications
- Inflammasome and immune disorders
Cornell University
2004-2017
Merck & Co., Inc., Rahway, NJ, USA (United States)
2014
New York State University College of Human Ecology
2014
The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.
The peptidylarginine deiminases (PADs) are a family of posttranslational modification enzymes that catalyze the conversion positively charged protein-bound arginine and methylarginine residues to uncharged, nonstandard amino acid citrulline. This enzymatic activity is referred as citrullination or, alternatively, deimination. Citrullination can significantly affect biochemical pathways by altering structure function target proteins. Five mammalian PAD members (PADs 1–4 6) have been described...
Abstract Background We have recently reported that the expression of peptidylarginine deiminase 2 (PADI2) is regulated by EGF in mammary cancer cells and appears to play a role proliferation normal epithelium; however, PADI2 pathogenesis human breast has yet be investigated. Thus, goals this study were examine whether plays tumor progression, inhibition PADI activity anti-tumor effects. Methods RNA-seq data from collection 57 cell lines was queried for levels, correlations with known subtype...
PAD4-mediated hypercitrullination of histone H4 arginine 3 (H4R3) has been previously found to promote the formation Neutrophil Extracellular Traps in inflamed tissues and resulting citrulline (H4Cit3) modification is thought play a key role extracellular trap (ET) by promoting chromatin decondensation. In addition neutrophils, macrophages have also recently generate functional traps (METs). However, for PADs ET not described. Transcripts PAD2 PAD4 are mature these cells can be induced...
Cone degeneration (cd ) is an autosomal recessive canine disease that occurs naturally in the Alaskan Malamute and German Shorthaired Pointer breeds. It phenotypically similar to human achromatopsia, a heterogeneous disorder associated with three distinct loci. Both its counterparts are characterized by day-blindness absence of retinal cone function adults. We report linkage cd locus marker C29.002 on chromosome 29 at recombination fraction 𝛉=0.0 maximum LOD score 24.68 series informative...
The peptidylarginine deiminase (PAD) family of enzymes post-translationally convert positively charged arginine residues in substrate proteins to the neutral, non-standard residue citrulline. PAD members 1, 2, 3, and 6 have previously been localized cell cytoplasm and, thus, their potential regulate gene activity has not described. We recently demonstrated that PAD2 is expressed canine mammary gland epithelium levels histone citrullination this tissue correlate with expression. Given these...
Both cyclic AMP (cAMP)/protein kinase A (PKA) and calcium (Ca(2+)) signaling pathways are known to be involved in the regulation of motility mammalian sperm. Calmodulin (CaM) is a ubiquitous Ca(2+) sensor that has been implicated acrosome reaction. In this report, we identify an insoluble pool CaM sperm show protein, addition its presence acrosome, found principal piece flagellum. These findings consistent with, though not proof of, fibrous sheath. The Ca(2+)/CaM-dependent protein IIbeta...
Abstract Lipid rafts, membrane sub‐domains enriched in sterols and sphingolipids, are controversial because demonstrations of rafts have often utilized fixed cells. We showed living sperm that the ganglioside G M1 localized to a micron‐scale sub‐domain plasma overlying acrosome. investigated four models proposed for maintenance. segregation was maintained live incubated under non‐capacitating conditions, after sterol efflux, alteration necessary capacitation. The complete lack diffusion...
We previously showed that in live murine and bovine sperm heads, the ganglioside G(M1) localizes to sterol-rich plasma membrane overlying acrosome (APM). Labeling using pentameric cholera toxin subunit B (CTB) induced a dramatic redistribution of signal from APM sterol-poor postacrosomal (PAPM) upon death. now show similar phenomenon flagellum where CTB induces subdomains annulus flagellar zipper. Because sterol efflux is required for capacitation, we examined whether localization might be...
Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using mouse model ductal carcinoma situ, we previously found that inhibition peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain integrity xenograft tumors. The goal this investigation was gain insight into mechanisms which PAD2 mediates process. For our study, modulated lentiviral shRNA-mediated depletion, lentiviral-mediated overexpression, or PAD and...
Peptidylarginine deiminase 2 (PAD2/PADI2) has been implicated in various inflammatory diseases and, more recently, cancer. The goal of this study was to test the hypothesis that PAD2 promotes oncogenesis using a transgenic mouse model. We found about 37% mice overexpressing human FLAG-PAD2 downstream MMTV-LTR promoter develop spontaneous neoplastic skin lesions. Molecular and histopathologic analyses resulting lesions find they contain increased levels markers for invasion, inflammation,...
Abstract Background Forward genetic screens in mice provide an unbiased means to identify genes and other functional elements the genome. Previously, a large scale ENU mutagenesis screen was conducted query content of ~50 Mb region mouse genome on proximal Chr 5. The majority phenotypic mutants recovered were embryonic lethals. Results We report high resolution mapping, complementation analyses, positional cloning mutations target region. collection identified alleles include several with...
Abstract Peptidylarginine deiminases (PADIs) enzymes are calcium-dependent that post-translationally convert positively charged protein arginine residues to a neutrally citrulline in process known as citrullination or deimination. This loss of charge can alter the tertiary structure proteins and affect protein-protein protein-DNA interactions. We, others, have found PADI-mediated histone tail alters chromatin regulates gene expression. For example, we PADI2 interacts with estrogen receptor...
<p>Supplementary Data: Figures and Tables Legend</p>
<p>Supplementary Figure 4: Human PAD2 expression, along with Mouse Pad1, Pad2, Pad3, and Pad4 expression levels in transgenic mice</p>