A5100383872- Glioma Diagnosis and Treatment
- Hedgehog Signaling Pathway Studies
- Microtubule and mitosis dynamics
- Estrogen and related hormone effects
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Fatty Acid Research and Health
- Chromatin Remodeling and Cancer
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- RNA Interference and Gene Delivery
- Inflammatory mediators and NSAID effects
- Protein Degradation and Inhibitors
- Cancer, Lipids, and Metabolism
- Nanoplatforms for cancer theranostics
- Ultrasound and Hyperthermia Applications
- Peptidase Inhibition and Analysis
- MicroRNA in disease regulation
- Multiple Myeloma Research and Treatments
- Mass Spectrometry Techniques and Applications
- Extracellular vesicles in disease
- Hippo pathway signaling and YAP/TAZ
- Advanced Proteomics Techniques and Applications
- Cell Adhesion Molecules Research
Emory University
2011-2024
Children's Healthcare of Atlanta
2024
Huazhong University of Science and Technology
2023
Tongji Hospital
2023
Center for Cancer and Blood Disorders
2019-2020
Children's Center
2014
Oglethorpe University
2012
Zero to Three
2004
Focused ultrasound–mediated delivery of RNA-loaded nanoparticles increases brain tumor cell apoptosis through oncogene targeting.
Abstract Treatment for medulloblastoma (MB) — the most common malignant pediatric brain tumor includes prophylactic radiation administered to entire and spine due high incidence of metastasis central nervous system. However, majority long-term survivors are left with permanent debilitating neurocognitive impairments as a result this therapy, while remaining 30–40% patients relapse terminal metastatic disease. Development more effective targeted therapies has been hindered by our lack...
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...
Abstract Background Metastasis in medulloblastoma (MB) is associated with poor survival. Recent genetic studies revealed MB to comprise distinct molecular subgroups, including the sonic hedgehog (SHH) subgroup that exhibits a relatively high rate of progression. To identify targeted therapeutics against metastasis, better understanding regulation cell migration needed. G protein-coupled receptor kinases (GRKs) have been implicated cancer metastasis through their G-protein coupled receptors...
Background Mismatch repair deficiency (dMMR) is a well-recognized biomarker for response to immune checkpoint blockade (ICB). Strategies convert MMR-proficient (pMMR) dMMR phenotype with the goal of sensitizing tumors ICB are highly sought. The combination bromodomain containing 4 (BRD4) inhibition and provides promising antitumor effect. However, mechanisms underlying remain unknown. Here, we identify that BRD4 induces persistent in cancers. Methods We confirmed correlation between mismatch...
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...
Sonic hedgehog subtype of medulloblastoma (SHH MB) with metastasis or specific clinical molecular alteration shas a poor prognosis and current therapy results in long-term cognitive impairment the majority survivors. Thus, great need exists for new targeted therapeutic approaches to more effectively treat SHH MB children. Imipramine blue (IB), novel molecule anti-tumor properties, inhibits NADPH oxidase (NOX) family enzymes, which are critical survival treatment resistance. In this study, IB...
Abstract Medulloblastoma is the most common malignant pediatric brain tumor with a for certain molecular subgroups very low overall survival and therefore an urgent need novel treatment approaches. Dordaviprone (ONC201) its chemical derivative nanomolar potency ONC206 are inhibitors of dopamine receptor 2 (DRD2) more importantly induce apoptosis cancer cells by activation mitochondrial caseinolytic protease P (ClpP). ONC201 has shown objective responses in patients diffuse midline gliomas...
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 Aurora kinases play an important role in regulating cell mitotic division. It has been found that they are over expressed many human cancers, and decreased expression either kinase A or B levels lead to apoptosis. suggested inhibitors might be attractive molecular target of anticancer therapy. AT9283, a multi-targeted inhibitor with potent activity against both B, is currently being evaluated clinical trails patients advanced hematological malignancies including AML. However date,...
Abstract RNA-based therapies offer unique advantages for treating pediatric brain tumors. However, the systemic delivery remains a major problem due to degradation of unmodified RNA in biological fluids, poor accumulation, and cancer cell uptake or escape from endosomal lipid bilayer barrier. While nanoparticle encapsulation can prolong circulation time facilitate cellular uptake, their accumulation tumor particularly low permeability across blood-brain barrier limited intratumoral...
Abstract Src kinase is overexpressed in many human cancers, including medulloblastoma (MB), the most common malignant pediatric brain tumor. plays a central role oncogenic signaling pathways, and has been implicated cell migration. Recently, we observed that blockade of aurora kinases A B, which regulate cycle progression are expressed by MB cells, also inhibits proliferation Because metastatic disease such powerful predictor survival patients, hypothesized combined inhibition may act...
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Current treatment involves multi-agent chemotherapy and/or radiation, but this one-size-fits-all often results in long term side effects. The development of novel therapeutics has been slowed, limited by lack representative samples individual patient MB; therefore, we adapted a drug testing assay to address issue: organotypic ex vivo tumor slice culture (OSC). We hypothesize that OSC can be robust real-time screening...
Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children. Of four different sub-groups, Sonic Hedgehog (SHH) subgroup accounts for about 30% of human MBs. The current standard care (resection, cranio-spinal irradiation, and chemotherapy) MB typically ineffective SHH non-infants those with metastatic disease. Survivors are frequently beset long-term side effects including cognitive deficiencies a severely impaired quality life. Taken together, there critical need...
Abstract Treatment for medulloblastoma (MB) is typically ineffective MYC amplified or metastatic SHH, Group 3 and 4 subgroups. Promising preclinical clinical results have been obtained adult pediatric malignant glioma treated with ONC-201, a selective antagonist of DRD2, G-protein coupled receptor that regulates prosurvival pathways. Herein, we report the activity ONC-201 ONC-206, which has increased non-competitive antagonism against MB. We three different MB cell types representative SHH-...
Abstract Treatment for medulloblastoma (MB) is typically ineffective MYC amplified or metastatic SHH, Group 3 and 4 subgroups. Promising preclinical clinical results have been obtained in brain cancers treated with ONC-201, a selective antagonist of DRD2, G-protein coupled receptor that regulates prosurvival pathways. Herein, we report the activity ONC-201 ONC-206, which has increased non-competitive antagonism against MB. We three different MB cell types representative SHH- 3-like cells,...