A5080667786- Hedgehog Signaling Pathway Studies
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Corneal Surgery and Treatments
- Hippo pathway signaling and YAP/TAZ
- Mycobacterium research and diagnosis
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Nerve injury and regeneration
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Wnt/β-catenin signaling in development and cancer
- Tuberculosis Research and Epidemiology
- Cancer, Hypoxia, and Metabolism
- DNA Repair Mechanisms
- Cancer Cells and Metastasis
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
- Cellular Mechanics and Interactions
- 3D Printing in Biomedical Research
- Nuclear Receptors and Signaling
- Genomics and Phylogenetic Studies
- Cancer, Lipids, and Metabolism
Emory University
2015-2023
Albert Einstein College of Medicine
2020
Duke Medical Center
2013
University of Illinois Chicago
2013
Dana-Farber Cancer Institute
2013
Stanford University
2013
Tokyo National Hospital
2013
Centre Eugène Marquis
2013
Hospital Universitari Germans Trias i Pujol
2013
Comprehensive Cancer Center Vienna
2013
Significance This study shows that an engineered biomimetic nanoparticle decorated with a targeting ligand and loaded sonic hedgehog inhibitor maintains its stability in the circulation, crosses blood–brain barrier (BBB), delivers drug molecules to cancer stem-like cell population subtype of medulloblastoma. Leveraging natural capabilities high-density lipoprotein, our enables facilitated targeted cellular uptake drugs receptor-mediated intracellular cholesterol depletion medulloblastoma...
Rifampicin and its derivatives are at the forefront of current standard chemotherapeutic regimen for active tuberculosis; they act by inhibiting transcription activity prokaryotic RNA polymerase. is believed to interact with beta subunit However, it has been observed that protein-protein interactions polymerase core enzyme lead reduced susceptibility rifampicin. This mechanism became more diversified discovery RbpA, a novel polymerase-binding protein, in Streptomyces coelicolor could...
Sonic hedgehog (Shh) signaling is closely coupled with bioenergetics of medulloblastoma, the most common malignant pediatric brain tumor. Shh-associated medulloblastoma arises from cerebellar granule neuron precursors (CGNP), a neural progenitor whose developmental expansion requires by Shh, ligand secreted neighboring Purkinje neurons. Previous observations show that Shh inhibits fatty acid oxidation although driving increased synthesis. Proliferating CGNPs and mouse medulloblastomas...
The protein MsRbpA from Mycobacterium smegmatis rescues RNA polymerase (RNAP) the inhibitory effect of rifampicin (Rif). We have reported previously that interacts with β-subunit RNAP and on Rif-resistant (Rif(R)) is minimal. Here we attempted to gain molecular insights into mechanism action this respect its role in rescuing Rif-mediated transcription inhibition. Our experimental approach comprised multiple-round assays, fluorescence spectroscopy, MS surface plasmon resonance order meet...
Sonic hedgehog (Shh)‐driven medulloblastoma (Shh MB) cells are dependent on constitutive Shh signaling, but targeted treatment of MB has been ineffective due to drug resistance. The purpose this study was address the critical role signal transducer and activator transcription 3 (STAT3) in signaling resistance cells. Herein, we show that STAT3 is required for Smoothened (Smo)‐dependent and, turn, reciprocally regulated by demonstrate activity expression HCK proto‐oncogene, Src family tyrosine...
The purpose of this study was to determine the efficacy nanoparticle-encapsulated Fidgetin-like 2 (FL2) siRNA (FL2-NPsi), a novel therapeutic agent targeting
Abstract Y-box binding protein 1 ( YBX1 or YB1) is a therapeutically relevant oncoprotein capable of RNA and DNA mediating protein–protein interactions that drive proliferation, stemness, resistance to platinum-based therapies. Given our previously published findings, the potential for YB1-driven cisplatin in medulloblastoma (MB), limited studies exploring YB1-DNA repair interactions, we chose investigate role YB1 radiation MB. MB, most common pediatric malignant brain tumor, treated with...
Abstract Background Xenotropic murine leukemia virus (MLV)-related (XMRV) is a gammaretrovirus that was discovered in prostate cancer tissues. Recently, it has been proposed XMRV laboratory contaminant and may have originated via rare recombination event. Host restriction factor APOBEC3G (A3G) reported to severely restrict replication human peripheral blood mononuclear cells. Interestingly, infects replicates efficiently cells of epithelial origin. It due lack off or very low levels A3G...
Rifampicin is an acknowledged inhibitor of bacterial RNA polymerase. We observed that there exists a substantial variation in the basal-level tolerance to rifampicin across microbial species. A number mechanisms have come light which depict molecular aspects behavior individual cell towards rifampicin. This review assesses current knowledge about and conjectures probable remain unexplored.
The role of RbpA in the backdrop M. smegmatis showed that it rescues mycobacterial RNA polymerase from rifampicin-mediated inhibition (Dey et al., 2010; Dey 2011). Paget and co-workers (Paget 2001; Newell 2006) have revealed homologs occur exclusively actinobacteria. al. (2006) MtbRbpA, when complemented a ∆rbpA mutant S. coelicolor, low recovery MIC (from 0.75 to 2 μg/ml) as compared complementation by native coelicolor (MIC increases 11 μg/ml). Our studies on MsRbpA show is differential...
Ikaros, a DNA-binding protein also known as Ikaros family zinc finger 1 (IKZF1), was initially shown to function critically in hematopoietic differentiation.Deletion or mutation of has been associated with lymphoblastic, well acute and chronic myelogenous leukemias demonstrating that can act tumor suppressor.Ikaros is predominantly expressed variety tissue including the brain, suggesting may be involved physiological functions glial growth.Other recent studies have regulate transition neural...
Abstract Metastasis is one of the deadliest aspects cancer. Initial Metastatic spread dependent on detachment and dissemination cells from a parent tumor, invasion into surrounding tissue. In this study, we characterize kinesin-8 member Kif19 as promoter cancer cell that suppresses cell-cell adherens junctions cell-matrix focal adhesions. analysis publicly available patient data sets demonstrated expression correlates with worse overall survival probability in several cancers increased...
Abstract The purpose of this study is to determine the efficacy STAT3 inhibitor WP1066 on sonic-hedgehog (SHH) subtype medulloblastoma (MB). STAT3, or signal transducer and activator transcription 3, a potential novel target for treatment SHH-MB. We have generated substantial preliminary data showing that activation promotes survival SHH-MB cancer stem cells (CSCs) are critical resistance tumor recurrence. Smoothened (SMO) antagonists shown in treating subtypes SHH-MB, however all tumors...
Abstract Downstream of mitogenic Sonic hedgehog (Shh) signaling, Yes-Associated Protein (YAP) can drive proliferation in Cerebellar Granule Neural Progenitor (CGNP) cells. CGNPs are the proposed cells origin SHH medulloblastomas. They a neural progenitor type whose developmental expansion requires signaling by Shh, secreted ligand produced neighboring Purkinje neurons. Approximately 30% human medulloblastomas bear an activated pathway gene expression signature. Ectopic YAP promotes highly...
Abstract Sonic hedgehog (Shh)-mediated medulloblastoma growth requires IGF2 (Insulin-like Growth Factor 2) and we recently showed that Yes Associated Protein (YAP1) induces expression by Y-box protein 1(YB1) in Shh-stimulated cerebellar granule neural precursors (CGNPs), proposed cells-of-origin for the Shh molecular subclass of medulloblastoma, mouse Shh-medulloblastoma cells. We found elevated levels YAP1, YB1 tumor cells occupying peri-vascular niche, a microenvironmental niche to house...
Sonic hedgehog (Shh)-mediated medulloblastoma growth requires IGF2 (Insulin-like Growth Factor 2) and we have shown that over-expression of Yes Associated Protein (YAP1) induces expression as a part YAP’s radiation resistance mechanism in mouse Shh-medulloblastoma cells Shh-induced cerebellar granule neural precursors (CGNPs), proposed cells-of-origin for the SHH molecular subclass (1). The peri-vascular niche, microenvironmental niche to house so-called tumor re-populating survive...
Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Current treatments leave majority survivors with long term cognitive impairment; thus, more effective tumor-targeting strategies are needed. Unfortunately, in vivo preclinical drug testing cumbersome, time consuming, and relies on vitro screens, which lack microenvironment. To counter these issues, we developed a new assay, organotypic ex slice culture, retains microenvironment, thus hypothesize will be robust...
<p>Supplementary Figures</p>
<p>Supplementary Figure S1: (a) mRNA expression analysis of Mfn1, Mfn2 and Drp1 genes was carried out in CGNPs. No significant changes were observed between the levels vehicle Shh treated (b) Automated quantification, using ImageJ software, CGNPs {plus minus}Shh, stained with Tom20. Supplementary S2: (a,c) over-expressing Mfn1 or 2, mitotracker Red. (b,d) Quantification proliferating cell numbers after BrdU incorporation 2. S3: Drp1, Drp1. S4: (a,b) 2 Red.</p>