A5015853909- HER2/EGFR in Cancer Research
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- Extracellular vesicles in disease
- Estrogen and related hormone effects
- Medicinal Plant Pharmacodynamics Research
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Cancer-related gene regulation
- Growth Hormone and Insulin-like Growth Factors
- Cancer Cells and Metastasis
- Drug Transport and Resistance Mechanisms
- Neuroscience and Neuropharmacology Research
- Peptidase Inhibition and Analysis
- Protein Interaction Studies and Fluorescence Analysis
- Cancer-related Molecular Pathways
- T-cell and B-cell Immunology
- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- PARP inhibition in cancer therapy
- Pesticide Exposure and Toxicity
- Barrier Structure and Function Studies
- Nutrition and Health in Aging
- Cancer survivorship and care
- Protein Degradation and Inhibitors
- Metabolism, Diabetes, and Cancer
Park Nicollet Methodist Hospital
2023
Johns Hopkins University
2016-2020
University Health Network
2007
Abstract Drug development for the treatment of central nervous system (CNS) diseases is extremely challenging, in large part due to difficulty crossing blood-brain barrier (BBB). Here we develop and experimentally validate a new silico method predict quantitatively BBB permeability small-molecule drugs. We show accurate prediction solute permeabilities at physiological temperature using high-temperature unbiased atomic detail molecular dynamics simulations spontaneous drug diffusion across...
Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration brain following systemic injection. To assess 2-PAM transport, we studied transwell permeability three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human microvascular endothelial cells (BC1-hBMECs). determine whether is substrate common efflux pumps,...
Brain microvascular endothelial cells derived from induced pluripotent stem (dhBMECs) are a scalable and reproducible resource for studies of the human blood–brain barrier, including mechanisms strategies drug delivery. Confluent monolayers dhBMECs recapitulate key in vivo functions tight junctions to limit paracellular permeability efflux nutrient transport regulate transcellular permeability. Techniques cryopreservation have been reported; however, functional validation after long-term not...
CXCR4 plays significant roles in immune and inflammatory responses is important for selective recruitment of leukocytes. We previously showed that surface expression human lymphocytes was affected by sulfatide, an vivo ligand L-selectin. Increased shown to promote biologically relevant functions such as integrin-dependent adhesion transmigration. Here, we show sulfatide-induced up-regulation also occurs on other leukocyte subsets humans mice. B cells CD4(+)CD25(+) T had the highest after...
<h3>Background</h3> Wnt/β-catenin pathway mutations correlate with immune exclusion across different tumor types, however the mechanism of β-catenin suppression is not fully understood. ST316 a peptide antagonist interaction between and BCL9 that currently in Phase 1/2 clinical study (NCT05848739). demonstrates potent anti-tumor activity preclinical Wnt/β-catenin-driven colorectal (CRC) triple-negative breast cancer (TNBC) models. Here we assessed impact on immunosuppressive myeloid cell...
Abstract Transcription factor dysregulation is common in cancer, resulting aberrant gene expression that drives oncogenesis. Antagonism of oncogenic transcription activity, by disrupting essential protein-protein interactions needed for activation downstream effector molecules or association with DNA, represents a powerful approach to target this previously ‘undruggable' class proteins. CCAAT/Enhancer Binding Protein Beta (C/EBPβ) overexpressed many cancers regulates factors promote tumor...
Abstract Aberrant activation of the canonical Wnt signaling pathway occurs in a variety cancers, resulting overactivation β-catenin-mediated transcriptional activity and increased expression genes that promote tumor survival, proliferation inhibit differentiation. Disruption β-catenin transcription complex, by inhibiting protein-protein interactions required for its formation, represents powerful approach to this previously ‘undruggable' target. The goal these experiments is characterize...
Abstract β-catenin is an oncogenic transcription factor that has essential role in cell development and biology. Increased expression or activity been implicated many cancers, including breast colorectal, associated with poor prognosis. Despite extensive ongoing research, conventionally considered ‘undruggable', there are no current drugs available to target Wnt/β-catenin signaling. B-cell CLL/lymphoma 9 protein (BCL9) a positive regulator of transcriptional overexpressed tumors. Disruption...
Abstract Breast cancer (BC) is the most common invasive in women, with more than 2.1 million cases and over 626,000 deaths occurring worldwide annually. Although age-adjusted mortality from BC has been declining since 1990, median survival for patients metastatic disease remains at 2-3 years, 5-year approximates 25%. Thus, medical need effective agents this clinical setting very high. CCAAT/Enhancer Binding Protein Beta (C/EBPβ) a transcription factor overexpressed many cancers that...
Abstract CCAAT/Enhancer Binding Protein Beta (C/EBPß) is a transcription factor overexpressed in glioblastoma (GBM). Mechanistically, C/EBPß master regulator of mesenchymal transition GBM, and its increased expression correlates with differentiation predicts poor clinical outcome. activity requires dimerization co-factors such as CREB/ATF family members via leucine zipper interactions. ST101 novel peptide antagonist currently being evaluated Phase 1/2 study patients advanced unresectable...