A5072551137- Protein Kinase Regulation and GTPase Signaling
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Cancer Treatment and Pharmacology
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Fatty Acid Research and Health
- Phytoestrogen effects and research
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Nanoplatforms for cancer theranostics
- Metabolomics and Mass Spectrometry Studies
- Chronic Myeloid Leukemia Treatments
- Mechanisms of cancer metastasis
- Microtubule and mitosis dynamics
- Wnt/β-catenin signaling in development and cancer
- Inflammatory Bowel Disease
- Cellular Mechanics and Interactions
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
National Center for Advancing Translational Sciences
2015-2024
National Institutes of Health
2018-2022
University of North Carolina Health Care
2019
Northwestern University
2019
University of Kansas
2019
Leidos (United States)
2019
Leidos Biomedical Research Inc. (United States)
2019
Tufts University
2019
National Cancer Institute
2012-2016
Center for Cancer Research
2012
Screening colonoscopy to monitor for early colitis-associated colon cancer (CAC) is difficult due the aberrant mucosal patterns associated with long-standing colitis. The aim of this study was develop a rapid fluorescent detection method use during improving CAC utilising topically applied enzymatically activatable probe (gGlu-HMRG) which fluoresces in presence γ-glutamyltranspeptidase (GGT), an enzyme cancer.Expression GGT cell lines examined fluorescence microscopy and flow cytometry. A...
A compound that reduces the prevalence of perinucleolar compartment in cancer cells inhibits metastasis vivo.
The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments epilepsy. current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) mice promotes phosphorylation, disrupting activity leads to fewer seizures, increases...
The transcription factor AP-1 (activator protein-1) regulates a number of genes that drive tumor promotion and progression. While basal levels activity are important for normal cell proliferation survival, overactivated AP-1-dependent gene expression stimulates inflammation, angiogenesis, invasion, other events propel carcinogenesis. We seek to discover targeted by carcinogenesis inhibitors do not also inhibit or survival. Transgenic TAM67 (dominant-negative c-Jun) inhibits mouse skin...
The perinucleolar compartment (PNC) is a dynamic subnuclear body found at the periphery of nucleolus. PNC enriched with RNA transcripts and RNA-binding proteins, reflecting different states genome organization. prevalence positively correlates cancer progression metastatic capacity, making it useful marker for progression. A high-throughput, high-content assay was developed to identify novel small molecules that selectively reduce in cells. We identified further optimized pyrrolopyrimidine...
Abstract The small GTPase Cdc42 is an integral component of the cytoskeleton, and its dysregulation leads to pathophysiological conditions, such as cancer. Binding scaffold protein IQGAP1 stabilizes in active form. interaction between enhances migration invasion cancer cells. Disrupting this association could impair neoplastic progression metastasis; however, no effective means achieve has been described. Here, we screened 78,500 compounds using a homogeneous time resolved fluorescence-based...
Metarrestin is a first-in-class small molecule clinical candidate capable of disrupting the perinucleolar compartment, subnuclear structure unique to metastatic cancer cells. This study aims define pharmacokinetic (PK) profile metarrestin and pharmacokinetic/pharmacodynamic relationship metarrestin-regulated markers. PK studies included administration single or multiple dose at 3, 10, 25 mg/kg via intravenous (IV) injection, gavage (PO) with chow wild-type C57BL/6 mice KPC bearing...
Small molecule based targeted therapies for the treatment of metastatic melanoma hold promise but responses are often not durable, and tumors frequently relapse. Response to adoptive cell transfer (ACT)-based immunotherapy in patients durable develop resistance primarily due loss antigen expression. The combination small molecules that sustain T effector function with ACT could lead long lasting responses. Here, we have developed a novel co-culture cell-based high throughput assay system...
Abstract The perinucleolar compartment (PNC) is a nuclear body that forms specifically in highly malignant cancer cells. PNC prevalence shown to reflect metastatic potential of cells from solid tissue origins. A high-content screen was performed identify small molecules reduce prevalence. Medicinal chemistry optimizations confirmed hits yield metarrestin, having 95% oral bioavailability and disassembly IC50 between 100 400 nM across multiple cell lines. Metarrestin inhibits soft agar growth...
Abstract Introduction: Consumption of dry beans and their fractions decrease colorectal neoplasia; however, the underlying molecular mechanisms are unclear. Aim study was to identify response indicators dietary attenuation tumorigenesis using metabolic profiling. Methods: The had a 2 x factorial design. After being either induced or not with azoxymethane/dextran sodium sulfate (AOM/DSS), male FVB/N mice were fed an AIN93G diet containing 0 (Control) 10% navy bean ethanol extract (BE) for 6...