A5053764983- Protein Tyrosine Phosphatases
- Lung Cancer Treatments and Mutations
- Tryptophan and brain disorders
- PI3K/AKT/mTOR signaling in cancer
- Cytokine Signaling Pathways and Interactions
- Treatment of Major Depression
- Chemical Reactions and Isotopes
- Synthesis and biological activity
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Respiratory viral infections research
- Bacteriophages and microbial interactions
- Radioactive contamination and transfer
- Biochemical and Molecular Research
- Immune cells in cancer
- Gene expression and cancer classification
- Radioactive element chemistry and processing
- Cardiac Arrest and Resuscitation
- interferon and immune responses
- Ultrasound in Clinical Applications
- Protein Kinase Regulation and GTPase Signaling
- Sports injuries and prevention
- Therapeutic Uses of Natural Elements
- Pneumonia and Respiratory Infections
- Nosocomial Infections in ICU
Indiana University School of Medicine
2023-2025
Indiana University – Purdue University Indianapolis
2023-2025
Asuragen (United States)
2024
Parker Hannifin (United States)
2024
Nottingham Trent University
2024
The University of Texas MD Anderson Cancer Center
2015-2021
Clemson University
2020
Src homology 2 domain-containing phosphatase (SHP2) is a that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and required for full activation the MAPK pathway. SHP2 inhibition has demonstrated tumor growth in RTK-activated cancers preclinical studies. The long-term effectiveness kinase inhibitors such as EGFR inhibitor (EGFRi), osimertinib, non-small cell lung cancer (NSCLC) limited by acquired resistance. Multiple clinically identified mechanisms underlie...
Abstract Background Implementation of automatic stop orders (ASOs) for empiric antimicrobials have reduced antimicrobial use without negatively impacting patient outcomes. Given a recent increase in meropenem at our tertiary referral pediatric hospital, 36-hour ASO option was implemented the EMR patients with sepsis requiring antibiotics active against ESBL-producing organisms. We sought to evaluate impact this initiative had on and safety Methods A October 12th, 2022. conducted...
Src homology 2 (SH2) domain-containing phosphatase (SHP2) plays a role in receptor tyrosine kinase (RTK), neurofibromin-1 (NF-1), and Kirsten rat sarcoma virus (KRAS) mutant-driven cancers, as well RTK-mediated resistance, making the identification of small-molecule therapeutics that interfere with its function high interest. Our quest to identify potent, orally bioavailable, safe SHP2 inhibitors led discovery promising series pyrazolopyrimidinones displayed excellent potency but had...
Indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme that mediates the rate-limiting step in metabolism of l-tryptophan to kynurenine, has been widely explored as potential immunotherapeutic target oncology. We developed class inhibitors with conformationally constrained bicyclo[3.1.0]hexane core. These potently inhibited IDO1 cellular context by binding apoenzyme, elucidated biochemical characterization and X-ray crystallography. A SKOV3 tumor model was instrumental...
Elite football is associated with the increased risk of illness, although targeted supplementation can reduce illness risk. This study assessed effects a supplement containing turmeric root within black pepper and fat-soluble blend, vitamin C D, on upper respiratory symptoms (URS), gastrointestinal (GIS), muscle soreness, markers inflammation gut permeability in elite male footballers. Twenty-three footballers completed 3 weeks no intervention (CON), followed by 16 daily consuming 60 mL...
Tumor-associated macrophages (TAMs) have a significant presence in the tumor stroma across multiple human malignancies and are believed to be beneficial growth. Targeting CSF1R has been proposed as potential therapy reduce TAMs, especially protumor, immune-suppressive M2 TAMs. Additionally, high expression of on cells associated with poor survival certain cancers, suggesting dependency therefore therapeutic target. The CSF1-CSF1R signaling pathway modulates production, differentiation,...
Existing targeted cystic fibrosis screening assays miss important pathogenic CFTR variants in the ethnically diverse US population.
Carrier screening identifies couples at risk for having a child with severe genetic disorder. Although NGS is widely used method carrier screening, it fails to resolve many problematic genes recommended in professional practice guidelines that have GC-rich repeats, structural variation, and pseudogenes. This necessitates the use of multiple specialized workflows remain limited their coverage pathogenic variation.
Increased expression of IDO1 is believed to create a tumor microenvironment that immunosuppressive. In the course our research directed at identifying potent and selective inhibitors IDO1, we identified class compounds inhibited activity in cellular context, but not isolated enzymatic assays. We have conducted detailed mechanistic studies shown these molecules inhibit by binding apo-enzyme, thus preventing incorporation heme-cofactor into active site holo-enzyme.Through an extensive...
Abstract Osimertinib, a third generation EGFR inhibitor, is front-line therapy for mutated non-small lung cancer (NSCLC). The long-term effectiveness of osimertinib limited by acquired resistance. Clinically identified resistance mechanisms include EGFR-dependent such as mutations on that preclude drug binding, and EGFR-independent activation the MAPK pathway, instance via alternate RTKs. It has also been noted frequently tumor from single patient harbors more than one mechanism, plasticity...
Abstract Increased expression of IDO1 is believed to create a tumor microenvironment that immunosuppressive. In the course our research directed at identifying potent and selective inhibitors IDO1, we identified class compounds inhibited activity in cellular context, but not isolated enzymatic assays. We have conducted detailed mechanistic studies shown these molecules inhibit by binding apo-enzyme, thus preventing incorporation heme-cofactor into active site holo-enzyme. Through an...
Abstract MTH1 is a protein that sanitizes oxidized dNTPs in the cell. It preferentially hydrolyzes 8-oxo-dGTP and 2-OH-dATP to their corresponding monophosphates thereby prevents incorporation of nucleotides into DNA or RNA. The functional result reduction down-stream mutations, damage, thus preventing cell death. Recent publications suggest non-essential enzyme normal cells, but required for survival cancer cells as consequence being subjected high levels oxidative stress; hence its...
<div>Abstract<p>Src homology 2 domain-containing phosphatase (SHP2) is a that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and required for full activation the MAPK pathway. SHP2 inhibition has demonstrated tumor growth in RTK-activated cancers preclinical studies. The long-term effectiveness kinase inhibitors such as EGFR inhibitor (EGFRi), osimertinib, non–small cell lung cancer (NSCLC) limited by acquired resistance. Multiple clinically identified...
<div>Abstract<p>Src homology 2 domain-containing phosphatase (SHP2) is a that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and required for full activation the MAPK pathway. SHP2 inhibition has demonstrated tumor growth in RTK-activated cancers preclinical studies. The long-term effectiveness kinase inhibitors such as EGFR inhibitor (EGFRi), osimertinib, non–small cell lung cancer (NSCLC) limited by acquired resistance. Multiple clinically identified...
<p>Supplementary Materials and Methods Supplementary References Tables S1 to S3 legends Figures S4 legends</p>
<p>Supplementary Materials and Methods Supplementary References Tables S1 to S3 legends Figures S4 legends</p>
Abstract Indoleamine 2,3-dioxygenase (IDO1 and IDO2) tryptophan dioxygenase (TDO) are heme-containing enzymes that mediate the rate limiting step in oxidative degradation of L-tryptophan (L-TRP) to kynurenine (KYN) metabolites. Tryptophan catabolism through KYN metabolic pathway is now recognized as one many mechanisms involved tumor cell evasion immune surveillance system. Inhibition microenvironment can lead improved response growth suppression. Recently, clinical proof concept this...
Plutonium (Pu) redox cycling is known to occur in stratified lakes and ponds, with higher concentrations occurring the anoxic layers 1 .This increase of Pu water column likely involves re-mobilization from sediment immobilization due complexation organic carbon iron minerals.However, contribution microorganisms environmental fate transport little understood.In particular, microbial intracellular extracellular (exudates) products provide various metal binding sites for either mobilization or...