A5033932799- Extracellular vesicles in disease
- Gut microbiota and health
- Mosquito-borne diseases and control
- HIV Research and Treatment
- Amyotrophic Lateral Sclerosis Research
- Studies on Chitinases and Chitosanases
- Cancer Cells and Metastasis
- Probiotics and Fermented Foods
- Metabolomics and Mass Spectrometry Studies
- Cancer-related gene regulation
- Clostridium difficile and Clostridium perfringens research
- Renal Transplantation Outcomes and Treatments
- Melanoma and MAPK Pathways
- Alzheimer's disease research and treatments
- SARS-CoV-2 and COVID-19 Research
- Antifungal resistance and susceptibility
- COVID-19 Clinical Research Studies
- Synthesis and biological activity
- RNA modifications and cancer
- Inhalation and Respiratory Drug Delivery
- Biochemical Analysis and Sensing Techniques
- Neuroscience and Neuropharmacology Research
- Prion Diseases and Protein Misfolding
- Advanced Proteomics Techniques and Applications
- Epigenetics and DNA Methylation
University of North Carolina at Chapel Hill
2022-2025
University of North Carolina Health Care
2025
North Carolina State University
2021-2024
Communities In Schools of Orange County
2023
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has been responsible for numerous large-scale outbreaks in the last twenty years. Currently, there are no FDA-approved therapeutics any infection. CHIKV nonstructural protein 2 (nsP2), which contains cysteine protease domain, essential viral replication, making it an attractive target drug discovery campaign. Here, we optimized nsP2 (nsP2pro) biochemical assay screening of 6,120-compound cysteine-directed covalent fragment...
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has been responsible for numerous large-scale outbreaks in the last twenty years. Currently, there are no FDA-approved therapeutics any infection. CHIKV non-structural protein 2 (nsP2), which contains cysteine protease domain, essential viral replication, making it an attractive target drug discovery campaign. Here, we optimized nsP2 (nsP2pro) biochemical assay screening of 6,120-compound cysteine-directed covalent fragment...
Sleep is an essential behavior that supports lifelong brain health and cognition. Neuronal synapses are a major target for restorative sleep function locus of dysfunction in response to deprivation (SD). Synapse density highly dynamic during development, becoming stabilized with maturation adulthood, suggesting exerts distinct synaptic functions between development adulthood. Importantly, problems common neurodevelopmental disorders including autism spectrum disorder (ASD). Moreover, early...
Mycophenolate mofetil (MMF) is an important immunosuppressant prodrug prescribed to prevent organ transplant rejection and treat autoimmune diseases. MMF usage, however, limited by severe gastrointestinal toxicity that observed in approximately 45% of recipients. The active form the drug, mycophenolic acid (MPA), undergoes extensive enterohepatic recirculation bacterial β-glucuronidase (GUS) enzymes, which reactivate MPA from mycophenolate glucuronide (MPAG) within tract. GUS enzymes...
A critical step in studies of the intestinal microbiome using meta-omics approaches is preservation samples before analysis. Preservation essential for that measure gene expression, such as metaproteomics, which used to identify and quantify proteins microbiomes. Intestinal are typically stored by flash-freezing storage at -80°C, but some experimental setups do not allow immediate freezing samples. In this study, we evaluated methods preserve fecal metaproteomics analyses when possible. We...
Host kinases play essential roles in the host cell cycle, innate immune signaling, stress response to viral infection, and inflammation. Previous work has demonstrated that coronaviruses specifically target kinase cascades subvert responses infection rely upon activity phosphorylate proteins enhance replication. Given number of inhibitors are already FDA approved treat cancers, fibrosis, other human disease, they represent an attractive class compounds repurpose for host-targeted therapies...
Alzheimer's disease (AD) features progressive neurodegeneration and microglial activation that results in dementia cognitive decline. The release of soluble amyloid (Aβ) oligomers into the extracellular space is an early feature AD pathology. This can promote excitotoxicity activation. Microglia adopt several states with various functional outcomes. Protective have been identified response to Aβ plaque pathology vivo. However, role microglia immune mediators neurotoxicity induced by unclear....
Candida albicans is a growing health concern as the leading causal agent of systemic candidiasis, life-threatening fungal infection with mortality rate ∼40% despite best available therapy. Yck2, casein kinase 1 (CK1) family member, cellular target inhibitors YK-I-02 (YK) and MN-I-157 (MN). Here, multiplexed inhibitor beads paired mass spectrometry (MIB/MS) employing ATP-competitive were used to define selectivity these Yck2 across global C. proteome. The MIB matrix captured 89% known...
Growing evidence supports the importance of extracellular vesicle (EV) as mediators communication in pathological processes, including those underlying respiratory disease. However, establishing methods for isolating and characterizing EVs remains challenging, particularly samples. This study set out to address this challenge by comparing different EV isolation evaluating their impacts on yield, markers purity, proteomic signatures, utilizing equine/horse bronchoalveolar lavage Horses can...
The deubiquitinase USP7 is a critical regulator of tumorigenesis, known for stabilizing the MDM2-p53 pathway. Emerging evidence highlights USP7's p53-independent roles in proliferation and tumorigenesis. Triple negative breast cancers frequently inactivate p53 this disease subtype remains difficult to treat need new therapeutic options. Our study reveals that upregulated TNBC patient tumors. Importantly, genetic pharmacologic inactivation impaired tumor progression models. To explore USP7’s...
A promising drug target, SETDB1, is a dual methyl-lysine (Kme) reader and methyltransferase implicated in cancer neurodegenerative disease progression. To help understand the role of triple Tudor domain (3TD) its Kme reader, we first identify low micromolar potency small molecule ligand, UNC6535, which occupies simultaneously both TD2 TD3 binding sites. Further optimization leads to discovery UNC10013, covalent 3TD ligand targeting Cys385 SETDB1. UNC10013 potent with kinact/KI 1.0 × 106...
Candida albicans is a major cause of systemic candidiasis, severe fungal infection with ∼40% mortality rate. Yck2, casein kinase 1 (CK1) in C. albicans, targeted by antifungal inhibitors YK-I-02 (YK) and MN-I-157 (MN). Using multiplexed inhibitor beads mass spectrometry (MIB/MS), the selectivity these was determined across kinome. The MIB matrix captured 89% protein kinases, revealing that YK MN selectively engage three CK1 homologues (Yck2, Yck22, Hrr25) human p38α homologue (Hog1)....
Introduction Severe injury, including burn trauma, leads to profound immune dysfunction, yet the mechanisms driving these changes remain incompletely defined. This lack of understanding has hindered efforts modulate response effectively. Additionally, a clear biomarker profile guide clinicians in identifying patients at high risk for poor clinical outcomes is lacking. Extracellular vesicles (EVs) have emerged as novel mediators dysfunction various pathologies. Prior studies mouse models...
Abstract Both intrinsic and acquired resistance limit the depth duration of response to all clinically evaluated anti-KRAS therapies. Genetic mechanisms, identified in nearly half relapsed patients, include acquisition mutations that effectively restore KRAS-dependent activities. Reported non-genetic mechanisms signaling transcriptional activities support epithelial-to-mesenchymal transition (EMT) or cancer subtypes less responsive KRAS inhibition. We recently reported MYC amplification...
Introduction Severe injury, including burn trauma, leads to profound immune dysfunction, yet the mechanisms driving these changes remain incompletely defined. This lack of understanding has hindered efforts modulate response effectively. Additionally, a clear biomarker profile guide clinicians in identifying patients at high risk for poor clinical outcomes is lacking. Extracellular vesicles (EVs) have emerged as novel mediators dysfunction various pathologies. Prior studies mouse models...
Transactive response DNA-binding protein of 43 kDa (TDP-43) is a highly conserved, ubiquitously expressed nucleic acid-binding that regulates DNA/RNA metabolism. Genetics and neuropathology studies have linked TDP-43 to several neuromuscular neurological disorders including amyotrophic lateral sclerosis (ALS) frontotemporal lobar degeneration (FTLD). Under pathological conditions, mislocalizes the cytoplasm where it forms insoluble, hyper-phosphorylated aggregates during disease progression....
Extracellular vesicle (EV)-mediated intercellular communication significantly influences pulmonary cell health and disease, yet
The gut microbiome plays critical roles in human homeostasis, disease progression, and pharmacological efficacy through diverse metabolic pathways. Gut bacterial β-glucuronidase (GUS) enzymes reverse host phase 2 metabolism, turn releasing active hormones drugs that can be reabsorbed into systemic circulation to affect homeostasis promote toxic side effects. FMN-binding loop 1 microbial GUS proteins have been shown drive drug toxin reactivation. Here we report the structure-activity...
A promising drug target, SETDB1, is a dual Kme reader and methyltransferase, which has been implicated in cancer neurodegenerative disease progression. To help understand the role of triple Tudor domain (3TD) its reader, we first identified low micromolar small molecule ligand, UNC6535, occupies simultaneously both TD2 TD3 binding sites. Further optimization led to discovery UNC10013, covalent 3TD ligand targeting Cys385 SETDB1. UNC10013 potent with k
RA-0003022 (3) was identified as a high-quality covalent chemical probe for Chikungunya nsP2 cysteine protease (nsP2pro). Isoxazole 3 covalently captured the active site C478 and inactivated enzyme with kinact/Ki ratio of 6000 M-1s-1. A negative control analog RA-0025453 (4) retained warhead but demonstrated >100-fold decrease in inhibition. Isoxazoles 4 were stable cross wide range pH solution upon prolonged storage solids. The inactive across panel 23 human viral proteases remarkable...
Abstract Diet has strong impacts on the composition and function of gut microbiota with implications for host health. Therefore, it is critical to identify dietary components that support growth specific microorganisms in vivo . We used protein-based stable isotope fingerprinting (Protein-SIF) link microbial species their carbon sources by measuring each microbe’s natural 13 C content (δ C) matching available substrates. fed gnotobiotic mice, inoculated a member microbiota, diets which all...