A5009862052- Neuroblastoma Research and Treatments
- Traumatic Brain Injury Research
- Protein Degradation and Inhibitors
- Cancer, Hypoxia, and Metabolism
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- DNA Repair Mechanisms
- CAR-T cell therapy research
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Nanowire Synthesis and Applications
- Immune Cell Function and Interaction
- Chromatin Remodeling and Cancer
- PARP inhibition in cancer therapy
- Hippo pathway signaling and YAP/TAZ
National Cancer Institute
2022-2025
Center for Cancer Research
2023-2025
National Cancer Institute
2023
Abstract Temporal regulation of super-enhancer (SE) driven transcription factors (TFs) underlies normal developmental programs. Neuroblastoma (NB) arises from an inability sympathoadrenal progenitors to exit a self-renewal program and terminally differentiate. To identify SEs driving TF regulators, we use all-trans retinoic acid (ATRA) induce NB growth arrest differentiation. Time-course H3K27ac ChIP-seq RNA-seq reveal ATRA coordinated SE waves. that decrease with link stem cell development...
Noradrenergic neuroblastoma is characterized by a core transcriptional regulatory circuitry (CRC) comprised of transcription factors (TF) such as PHOX2B, HAND2, and GATA3, which form network with MYCN. At normal physiologic levels, MYCN mainly binds to promoters but when aberrantly upregulated in neuroblastoma, also enhancers. Here, we investigated how invades enhancers whether CRC TFs play role this process. HAND2 was found regulate chromatin accessibility assist binding Moreover,...
Chimeric antigen receptor (CAR) T cells effectively treat B cell malignancies. However, CAR-T cause inflammatory toxicities such as cytokine release syndrome (CRS), which is in contrast to (TCR)–engineered against various antigens that historically have rarely been associated with CRS. To study whether and how differences types affect the propensity for eliciting responses a model system wherein TCR CAR target equalized sources of clinically relevant antigen, we discovered CD22-specific...
Abstract The oncoprotein MYCN drives malignancy in various cancer types, including neuroblastoma (NB). However, our understanding of the mechanisms underlying its transcriptional activity and oncogenic function, as well effective strategies to target it, remains limited. We discovered that interacts with coactivator KAT2A, this interaction significantly contributes MYCN’s NB. Our genome-wide analyses indicate recruits KAT2A bind DNA, thereby transcriptionally regulating genes associated...
Abstract The neural crest lineage regulatory transcription factors (TFs) form a core circuitry (CRC) in neuroblastoma (NB) to specify noradrenergic tumor phenotype. Oncogenic subversion of CRC TFs is well documented, but the role loss suppressors plays remains unclear. Zinc-finger TF CASZ1 chromosome 1p36 (chr1p36) suppressor. Single-cell RNA sequencing data analyses indicate that highly expressed developing chromaffin cells coincident with an expression NB TFs. In cells, suppressor silenced...
<div>Abstract<p>Noradrenergic neuroblastoma is characterized by a core transcriptional regulatory circuitry (CRC) comprised of transcription factors (TF) such as PHOX2B, HAND2, and GATA3, which form network with MYCN. At normal physiologic levels, MYCN mainly binds to promoters but when aberrantly upregulated in neuroblastoma, also enhancers. Here, we investigated how invades enhancers whether CRC TFs play role this process. HAND2 was found regulate chromatin accessibility assist...
MYCN activates canonical MYC targets involved in ribosome biogenesis, protein synthesis and represses neuronal differentiation genes to drive oncogenesis neuroblastoma (NB). How orchestrates global gene expression remains incompletely understood. Our study finds that binds promoters up-regulate but both enhancers repress genes. MYCN-binding also increases H3K4me3 H3K27ac on target decreases promoters. WDR5 is needed facilitate promoter binding activate genes, whereas recruits G9a Targeting...
ABSTRACT Noradrenergic neuroblastoma (NB) is characterized by a core transcriptional regulatory circuitry (CRC) comprised of transcription factors (TFs) such as PHOX2B, HAND2 and GATA3, which form network with MYCN. Physiological levels MYCN mainly binds to promoters but aberrantly upregulated in NB also enhancers. How invades enhancers, what role the CRC TFs play this process unknown. Here we find that assists invade enhancers through an “ indirect cooperative ” TF-DNA binding mechanism....
<p>Table S5 shows genes regulated by HAND2 or MYCN in LAN5 cells.</p>
<p>Supplementary file contains 6 supplementary figures.</p>
<p>Table S8 shows genes altered after silencing both HAND2 and MYCN.</p>
<p>Table S7 shows HAND2 directly activated and repressed genes.</p>
<p>Table S4 shows genes regulated by HAND2 or MYCN in IMR32 cells.</p>
<p>Table S6 shows super-enhancers associated genes identified in siCtrl cells and siHAND2 cells.</p>
<p>Table S3 shows list of antibodies used in western blot and ChIP-seq.</p>
<p>Table S5 shows genes regulated by HAND2 or MYCN in LAN5 cells.</p>
<p>Table S1 shows primer sequences used for realtime PCR and HAND2 mutant sequence information.</p>
<p>Table S3 shows list of antibodies used in western blot and ChIP-seq.</p>
<div>Abstract<p>Noradrenergic neuroblastoma is characterized by a core transcriptional regulatory circuitry (CRC) comprised of transcription factors (TF) such as PHOX2B, HAND2, and GATA3, which form network with MYCN. At normal physiologic levels, MYCN mainly binds to promoters but when aberrantly upregulated in neuroblastoma, also enhancers. Here, we investigated how invades enhancers whether CRC TFs play role this process. HAND2 was found regulate chromatin accessibility assist...
<p>Table S7 shows HAND2 directly activated and repressed genes.</p>
<p>Table S6 shows super-enhancers associated genes identified in siCtrl cells and siHAND2 cells.</p>
<p>Supplementary file contains 6 supplementary figures.</p>
<p>Table S4 shows genes regulated by HAND2 or MYCN in IMR32 cells.</p>