A5103112979- Protein Tyrosine Phosphatases
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- ATP Synthase and ATPases Research
- Cancer Research and Treatments
- Heavy Metal Exposure and Toxicity
- Trace Elements in Health
- Advanced Fluorescence Microscopy Techniques
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Cancer therapeutics and mechanisms
- Multiple Myeloma Research and Treatments
- Heavy Metals in Plants
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Epigenetics and DNA Methylation
University of Kentucky
2017-2023
Markey Cancer Center
2020-2023
Abstract Chronic low dose inorganic arsenic (iAs) exposure leads to changes in gene expression and epithelial-to-mesenchymal transformation. During this transformation, cells adopt a fibroblast-like phenotype accompanied by profound changes. While many mechanisms have been implicated studies that focus on the role of epigenetic alterations process are just emerging. DNA methylation controls physiologic pathologic states. Several show patterns iAs-mediated pathogenesis, but these focused...
Abstract Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, small molecule inhibitors PRL-3 are lacking. Here, we screened 1443 FDA-approved drugs for their ability inhibit the activity PRL family. We identified five specific as well one selective inhibitor PRL-2. Additionally, found nine that broadly significantly suppressed...
Phosphatase of Regenerating Liver-3 (PRL-3) is associated with cancer progression and metastasis. The mechanisms that drive PRL-3’s oncogenic functions are not well understood, partly due to a lack research tools available study this protein. We have begun address these issues by developing alpaca-derived single domain antibodies, or nanobodies, targeting PRL-3 KD 30–300 nM no activity towards highly homologous family members PRL-1 PRL-2. found longer charged N-terminal tags on PRL-3, such...
ABSTRACT Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, there are currently no viable options target PRL-3 vivo . Here, we screened 1,443 FDA-approved drugs for their ability inhibit the activity PRL family. We identified five specific inhibitors as well one selective inhibitor PRL-2. Additionally, found nine that broadly...
Phosphatases are increasingly recognized as potential oncogenes in a variety of cancer types. Although phosphatases were largely thought to counteract the effect kinases, they for their ability modulate strength and duration signaling, even activate signaling cascades. As enzymes, represent novel useful class drug targets cancer, but date, there no FDA‐approved phosphatase inhibitors, only few clinical trials. I have developed 2‐pronged approach identifying that may serve specifically...
Abstract PRL-3 is an oncogenic phosphatase across multiple cancer types, including colon, ovarian, melanoma, breast, and leukemia. While there increasing interest in developing inhibitors for use research treatment, have been several issues designing small molecule PRL-3, such as a shallow, negative charged active site, homology between the site other protein tyrosine phosphatases, high degree of overall family members PRL-1 PRL-2. Nanobodies recently emerged immensely useful tool show...
Abstract Phosphatase of Regenerating Liver-3 (PRL-3) is associated with cancer progression and metastasis in various solid tumors leukemias. The mechanisms that drive PRL-3’s oncogenic functions are not well understood, part due to a lack research tools available study this protein. In particular, small molecules do exhibit binding specificity for PRL-3 over highly homologous family members PRL-1 PRL-2, antibodies directed against limited by assay type. We have begun address these issues...
Abstract Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3) is an oncogenic dual-specificity phosphatase that drives tumor metastasis, promotes cancer cell survival, and correlated with poor patient prognosis in a variety of solid tumors leukemias. The mechanisms drive PRL-3’s functions are not well understood, part due to lack research tools available study this protein. development such has proven difficult, as the PRL family ~80% homologous catalytic binding pocket shallow hydrophobic....
Abstract Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3) is an oncogenic dual specificity phosphatase that drives tumor metastasis, promotes cancer cell survival, and has been linked to poor patient prognosis in a variety of types. The mechanisms by which PRL-3 progression are not well understood, part due lack tools study this protein. There intense need for research-grade antibodies the PRL field. However, development such proven difficult, as family ~80% homologous catalytic binding...