A5084778817- Chromatin Remodeling and Cancer
- Protein Degradation and Inhibitors
- Computational Drug Discovery Methods
- Genomics and Chromatin Dynamics
- Mechanisms of cancer metastasis
- Cancer Mechanisms and Therapy
- Ocular Oncology and Treatments
- Cell Image Analysis Techniques
- Innovative Microfluidic and Catalytic Techniques Innovation
- bioluminescence and chemiluminescence research
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Advanced biosensing and bioanalysis techniques
- Retinal Development and Disorders
- Medical Imaging Techniques and Applications
- Colorectal Cancer Treatments and Studies
- Photoreceptor and optogenetics research
- CRISPR and Genetic Engineering
- Cancer Research and Treatments
- Genetics, Bioinformatics, and Biomedical Research
- Quantum Dots Synthesis And Properties
- Antimicrobial Peptides and Activities
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
Novartis (United States)
2017-2023
Novartis (Switzerland)
2022
Novartis Institutes for BioMedical Research
2022
Foundation for Biomedical Research
2019
Boston Biomedical Research Institute
2019
Johns Hopkins University
2011-2013
SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), is a Snf2-family DNA-dependent ATPase. BRM and its close Brahma-related gene 1 (BRG1), SMARCA4, are mutually exclusive ATPases the large ATP-dependent SWI/SNF chromatin-remodeling complexes involved in transcriptional regulation expression. No small molecules have been reported that modulate activity via inhibition ATPase activity, an important goal...
Malignant tumors can evade destruction by the immune system attracting immune-suppressive regulatory T cells (Treg) cells. The IKZF2 (Helios) transcription factor plays a crucial role in maintaining function and stability of Treg cells, deficiency reduces tumor growth mice. Here we report discovery NVP-DKY709, selective molecular glue degrader that spares IKZF1/3. We describe recruitment-guided medicinal chemistry campaign leading to NVP-DKY709 redirected degradation selectivity cereblon...
CuInxSeY/ZnS core/shell quantum dots are synthesized with an emission peak in the near IR and a high yield, suitable for biomedical imaging optical window. After lipid coating transferring to water, show good stability, retain their have relatively small sizes optimize circulation clearance post-injection (P.I.).
Various subunits of mammalian SWI/SNF chromatin remodeling complexes display loss-of-function mutations characteristic tumor suppressors in different cancers, but an additional role for supporting cell survival distinct cancer contexts is emerging. In particular, genetic dependence on the catalytic subunit BRG1/SMARCA4 has been observed acute myelogenous leukemia (AML), yet feasibility direct therapeutic targeting activity remains unknown. Here, we evaluated dual BRG1/BRM ATPase inhibitors...
Abstract Uveal melanoma is a rare and aggressive cancer that originates in the eye. Currently, there are no approved targeted therapies very few effective treatments for this cancer. Although activating mutations G protein alpha subunits, GNAQ GNA11, key genetic drivers of disease, additional drug targets have been identified. Recently, studies identified context-specific roles mammalian SWI/SNF chromatin remodeling complexes (also known as BAF/PBAF) various lineages. Here, we find evidence...
Abstract Members of the ATP-dependent SWI/SNF chromatin remodeling complexes are among most frequently mutated genes in cancer, suggesting their dysregulation plays a critical role. The synthetic lethality between catalytic subunits BRM/SMARCA2 and BRG1/SMARCA4 has instigated great interest targeting BRM. Here we have performed in-depth investigation novel dual inhibitors (BRM011 BRM014) BRM BRG1 order to validate utility as chemical probes function, while obtaining insights into therapeutic...
Abstract For a majority of patients with non–small cell lung cancer EGFR mutations, treatment inhibitors (EGFRi) induces clinical response. Despite this initial reduction in tumor size, residual disease persists that leads to relapse. Elucidating the preexisting biological differences between sensitive cells and surviving drug-tolerant persister deciphering how evolve response could help identify strategies improve efficacy EGFRi. In study, we tracked origins clonal evolution at high...
A current challenge in biomedical imaging is the synthesis of water-soluble quantum dots (QDs) with emission wavelength near-IR, high yield, stability water, and relatively small size. In addition, due to concerns over toxicity if QDs are not cleared from body, it desirable avoid elements such as cadmium, lead, arsenic. The cover image presents copper-indium-selenide a zinc-sulfide (ZnS) shell, which satisfy many these requirements. After functionalizing surface an alkanethiol monolayer...
Abstract Growing malignant tumors must evade destruction by the immune system, a hurdle some malignancies overcome attracting immune-suppressive regulatory T-cells (Tregs)1. The IKZF2 (Helios) transcription factor plays crucial role in maintaining function and stability of Tregs, deficiency enhances responses to mice2, suggesting may be an attractive target for cancer immunotherapy. Here we describe discovery characterization DKY709, first molecular glue degrader IKZF2/4 which spares...
Supplementary Figures 1-5 from ABCG2/BCRP Expression Modulates d-Luciferin–Based Bioluminescence Imaging
Supplementary Figures 1-5 from ABCG2/BCRP Expression Modulates d-Luciferin–Based Bioluminescence Imaging
<div>Abstract<p>Bioluminescence imaging (BLI) is becoming indispensable to the study of transgene expression during development and, in many <i>in vivo</i> models disease such as cancer, for high throughput drug screening vitro</i>. Because reaction d-luciferin with firefly luciferase (fLuc) produces photons sufficiently long wavelength permit intact animals, use this substrate and enzyme pair has become method choice performing BLI vivo</i>. We now show...
<div>Abstract<p>Bioluminescence imaging (BLI) is becoming indispensable to the study of transgene expression during development and, in many <i>in vivo</i> models disease such as cancer, for high throughput drug screening vitro</i>. Because reaction d-luciferin with firefly luciferase (fLuc) produces photons sufficiently long wavelength permit intact animals, use this substrate and enzyme pair has become method choice performing BLI vivo</i>. We now show...
<p>Supplementary Figure S1 shows additional shRNA knockdown data in uveal melanoma cell lines. Supplementary S2 dual BRG1/BRM and BRG1 rescue data. S3 basal SWI/SNF subunit expression, caspase activity viability compound treated lines, mutations cells S4 MITF further RNA-Seq ATAC-Seq set analyses. S5 target gene modulation by treatment lines overexpression S6 genomic location of primers used ChIP-qPCR experiment.</p>
<p>Additional method details for ATAC-Seq Data Analysis and ChIP-qPCR</p>
Supplementary Data from Exquisite Sensitivity to Dual BRG1/BRM ATPase Inhibitors Reveals Broad SWI/SNF Dependencies in Acute Myeloid Leukemia
Supplementary Data from Exquisite Sensitivity to Dual BRG1/BRM ATPase Inhibitors Reveals Broad SWI/SNF Dependencies in Acute Myeloid Leukemia
Supplementary Data from Exquisite Sensitivity to Dual BRG1/BRM ATPase Inhibitors Reveals Broad SWI/SNF Dependencies in Acute Myeloid Leukemia
Supplementary Data from Exquisite Sensitivity to Dual BRG1/BRM ATPase Inhibitors Reveals Broad SWI/SNF Dependencies in Acute Myeloid Leukemia
Supplementary Data from Exquisite Sensitivity to Dual BRG1/BRM ATPase Inhibitors Reveals Broad SWI/SNF Dependencies in Acute Myeloid Leukemia
<p>Supplementary Figure S1 shows additional shRNA knockdown data in uveal melanoma cell lines. Supplementary S2 dual BRG1/BRM and BRG1 rescue data. S3 basal SWI/SNF subunit expression, caspase activity viability compound treated lines, mutations cells S4 MITF further RNA-Seq ATAC-Seq set analyses. S5 target gene modulation by treatment lines overexpression S6 genomic location of primers used ChIP-qPCR experiment.</p>