A5070147442- Antimicrobial Peptides and Activities
- Biochemical and Structural Characterization
- Peptidase Inhibition and Analysis
- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- Signaling Pathways in Disease
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Carbohydrate Chemistry and Synthesis
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Protease and Inhibitor Mechanisms
- Rheumatoid Arthritis Research and Therapies
- Advanced biosensing and bioanalysis techniques
- Antimicrobial agents and applications
- S100 Proteins and Annexins
- Cancer Treatment and Pharmacology
- Enzyme function and inhibition
- ATP Synthase and ATPases Research
- Cancer-related gene regulation
- Advanced Chemical Sensor Technologies
- Sphingolipid Metabolism and Signaling
- Retinoids in leukemia and cellular processes
- Epigenetics and DNA Methylation
Middle Tennessee State University
2016-2025
Scripps Research Institute
2012-2015
University of South Carolina Sumter
2010-2012
University of South Carolina
2007-2011
Neutrophil extracellular traps containing citrullinated peptides promote inflammation in synovial fibroblasts.
Cofactors for estrogen receptor α (ERα) can modulate gene activity by posttranslationally modifying histone tails at target promoters. Here, we found that stimulation of ERα-positive cells with 17β-estradiol (E2) promotes global citrullination H3 arginine 26 (H3R26) on chromatin. Additionally, the citrulline (H3Cit26) modification colocalizes ERα decondensed chromatin loci surrounding estrogen-response elements Surprisingly, also H3R26 is catalyzed peptidylarginine deiminase (PAD) 2 and not...
Protein arginine deiminases (PADs) catalyze the hydrolysis of peptidyl to form citrulline. Abnormally high PAD activity is observed in a host human diseases, but exact role protein citrullination these diseases and identities specific citrullinated disease biomarkers remain unknown, largely because lack readily available chemical probes detect citrullination. For this reason, we developed citrulline-specific probe, rhodamine–phenylglyoxal (Rh–PG), which show can be used investigate This...
Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and routinely used for disease diagnosis. Protein citrullination is also increased in cancer other autoimmune disorders, suggesting that citrullinated proteins may serve as biomarkers diseases beyond RA. To identify these proteins, we developed biotin-conjugated phenylglyoxal (biotin-PG). Using this probe our platform technology, identified >50 intracellular proteins. More than 20 involved RNA splicing,...
The autotaxin–lysophosphatidic acid receptor (ATX-LPAR) signaling axis is pivotal in various clinical conditions, including cancer and autoimmune disorders. This promotes tumorigenicity by interacting with the tumor microenvironment, facilitating metastasis, conceding antitumor immunity, thereby fostering resistance to conventional therapies. Recent studies highlight promise of ATX/LPAR inhibitors combination chemotherapeutic drugs overcome some forms this resistance, representing a novel...
Peptide borono lectins (PBLs) have been synthesized and shown to bind glycoproteins dependant on the glycoprotein PBL structures. The binding is reversible it has demonstrated that both selective cross-reactive PBLs can be identified. potential utility of these as a cancer diagnostic demonstrated.
Aberrant glycosylation of cell membrane and secreted glycoproteins is a hallmark various disease states, including cancer. The natural lectins currently used in the recognition these are costly, difficult to produce, unstable toward rigorous use. Herein we describe design synthesis several boronic acid functionalized peptide-based synthetic lectin (SL) libraries, as well optimized methodology for obtaining peptide sequences SLs. SL libraries were subsequently identify SLs with high 5-fold...
Aberrant glycosylation is a hallmark of various disease states, including cancer, and effective detection discrimination between healthy diseased cells an important challenge for the diagnosis treatment many diseases. Here, we describe use boronic acid functionalized synthetic lectins (SLs) in array format differentiation structurally similar cancer associated glycans cell lines; based on subtle variations patterns. We further demonstrate utility our SLs recognizing glycoproteins with up to...
The protein arginine deiminases (PADs) are known to play a crucial role in the onset and progression of multiple inflammatory diseases, including rheumatoid arthritis, bowel disease, cancer. However, it is not how each five PAD isozymes contributes disease pathogenesis. As such, potent, selective, bioavailable inhibitors will be useful chemical probes elucidate specific roles isozyme. Since D-amino amino acids often possess enhanced cellulo stability, perhaps unique selectivities, we...
Rapid emergence of antimicrobial resistant organisms necessitates equally rapid methods for the development new compounds. Of recent interest have been mimics peptides known as peptoids, which exhibit similar potency to former but with improved proteolytic stability. Presented herein is a high-throughput method screen libraries peptoids immobilized on beads embedded into solid media. Termed peptoid library agar diffusion (PLAD) assay, this assay allows individual chemical manipulation two...
Studies show there is an increasing rate of fungal infections, especially in immunocompromised patients and treatments for genera, such as Aspergillus, Candida, Cryptococcus, carry significant cytotoxicity with prevalence antifungal resistance. We have previously reported a high-throughput assay identifying peptoids antimicrobial properties from combinatorial libraries. Here we report the application this peptoid against Cryptococcus neoformans. Termed AEC5, has comparable potency to...
The protein arginine deiminases (PADs) catalyze the post-translational hydrolysis of peptidyl-arginine to form peptidyl-citrulline in a process termed deimination or citrullination. PADs likely play role progression range disease states because dysregulated PAD activity is observed host inflammatory diseases and cancer. For example, recent studies have shown that PAD2 activates ERα target gene expression breast cancer cells by citrullinating histone H3 at ER promoters. To date, all known...
The dysregulation of protein arginine methyltransferases (PRMTs) is implicated in a wide variety disease states. Here we report the design, synthesis, and screening combinatorial peptide library used to characterize substrate specificity PRMT1. information gained from this approach was develop PRMT1 inhibitor with enhanced selectivity.
Cryptococcus neoformans is a fungal pathogen that causes cryptococcal meningitis in immunocompromised individuals. Existing antifungal treatment plans have high mammalian toxicity and increasing drug resistance, demonstrating the dire need for new, nontoxic therapeutics. Antimicrobial peptoids are one alternative to combat this issue. Our lab has recently identified tripeptoid, AEC5, with promising efficacy selectivity against C. neoformans. Here, we report studies into broad-spectrum...
Bacteria and fungi can secrete reside within a complex polysaccharide matrix, forming biofilm that protects these pathogens from the immune response conventional antibiotics. Because many microbial grow biofilms in clinical settings, there is need for antimicrobial agents effective against biofilm-protected infections. We report adaptation of phenotypic high-throughput assay discovering peptoids toward screening combinatorial libraries established biofilms. This method, termed Inverted...
A limited number of antifungals are available to treat infections caused by fungal pathogens such as Cryptococcus neoformans and Candida albicans. Current clinical generally toxic, increasing resistance these therapies is being observed, necessitating new, effective, safe antifungals. Peptoids, or N-substituted glycines, have shown promise antimicrobial agents against bacteria, fungi, parasites. Herein we report the discovery characterization an antifungal peptoid termed RMG8-8. This...
Cryptococcal meningitis, caused by the fungal pathogen Cryptococcus neoformans, is a devastating disease with mortality rate of over 80%. Due to increasing prevalence resistance antifungals and high mammalian toxicity current treatments, development new antifungal therapies vital. In an effort improve biological properties previously discovered peptoid, termed RMG8-8, iterative structure-activity relationship study was conducted. This three-round sought optimize structure RMG8-8 focusing on...