A5088441131- Kruppel-like factors research
- Neuroblastoma Research and Treatments
- Chronic Myeloid Leukemia Treatments
- CRISPR and Genetic Engineering
- Cancer, Hypoxia, and Metabolism
- Protein Degradation and Inhibitors
- Immune Response and Inflammation
- Sepsis Diagnosis and Treatment
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Streptococcal Infections and Treatments
- RNA regulation and disease
- Neuroendocrine Tumor Research Advances
- Ubiquitin and proteasome pathways
- Eosinophilic Disorders and Syndromes
- Cellular Mechanics and Interactions
- Cardiomyopathy and Myosin Studies
- Microbial Metabolic Engineering and Bioproduction
- Acute Myeloid Leukemia Research
- Immune cells in cancer
- RNA and protein synthesis mechanisms
- Bacterial Identification and Susceptibility Testing
- interferon and immune responses
- Renal Diseases and Glomerulopathies
- Acute Lymphoblastic Leukemia research
- Cancer-related gene regulation
Baylor College of Medicine
2016-2023
Children's Cancer Center
2017
Boston Medical Center
2016
Boston University
2016
Harvard University
2016
Abstract Many metabolic liver disorders are refractory to drug therapy and require orthotopic transplantation. Here we demonstrate a new strategy, which call pathway reprogramming, treat hereditary tyrosinaemia type I in mice; rather than edit the disease-causing gene, delete gene disease-associated render phenotype benign. Using CRISPR/Cas9 vivo , convert hepatocytes from into benign III by deleting Hpd (hydroxyphenylpyruvate dioxigenase). Edited ( Fah −/− /Hpd ) display growth advantage...
Several glomerular pathologies resulting from podocyte injury are linked to genetic variation involving the MYH9 gene, which encodes heavy chain of non‐muscle myosin‐IIA (NM‐IIA). However, functional role NM‐IIA has not been studied extensively in podocytes. We hypothesized that is critical for maintenance structure and mechanical function. To test this hypothesis, we murine podocytes vitro subjected blebbistatin inhibition NM‐II activity, or RNA interference‐mediated, isoform‐specific...
Tumor progression and resistance to therapy in children with neuroblastoma (NB), a common childhood cancer, are often associated infiltration of monocytes macrophages that produce inflammatory cytokines. However, the mechanism by which tumor-supportive inflammation is initiated propagated remains unknown. Here, we describe novel protumorigenic circuit between NB cells triggered sustained tumor necrosis factor alpha (TNF-α). We used knockouts (KOs) TNF-α TNFRSF1A mRNA (TNFR1)/TNFRSF1B (TNFR2)...
Abstract Introduction: Increasing evidence suggest that epigenetic regulators play a critical role in cancer cell heterogeneity and maintaining tumor sub-populations with enhanced tumor-initiating drug-resistant capacities. Recently, we discovered drug-resistant, highly tumorigenic, self-renewing sub-population features of stem cells (CSCs) pediatric neuroblastoma (NB). This sub-population, characterized by surface expression G-CSF receptor (CD114), can escape initial therapy cause...
Abstract Chronic myeloid leukemia (CML) is the first blood cancer known to originate from a single hematopoietic stem cell (HSC) by expression of BCR-ABL, product chromosomal translocation t(9;22), that slowly progress lethal fast-growing caused malignant reprogramming progenitor cells (blast crisis). Although CML can be successfully managed with targeted therapy suppressing BCR-ABL kinase activity tyrosine inhibitors (TKI), patients remain in remission as long they adhere lifelong...
Abstract Leukemia stem cells (LSCs) are a rare population able to sustain and recapitulate leukemia through poorly understood mechanism of self-renewal. Because more than half patients relapse after the cessation TKI therapy, it is clear that cure not possible with TKIs alone, LSC-specific drugs urgently needed simultaneously eliminate bulk LSCs. Here we report KLF4 promotes disease progression in chronic myeloid (CML) by repressing an inhibitory LSCs can be activated small molecules....
Abstract High-risk neuroblastoma (NB) represents a major clinical challenge in pediatric oncology. Despite significant dose escalation of intense therapies, long-term survival for NB patients remains poor (<45%), and the disease accounts almost 15% all cancer deaths. Relapse metastatic, drug-resistant treatment-related toxicities mandates development new therapeutic strategies. Recently, we discovered highly tumorigenic, chemoresistant, self-renewing subpopulation with features...
Abstract Neuroblastoma (NB) is a poorly differentiated, aggressive pediatric solid tumor for which half of high-risk cases have no identified genetic alteration. While such tumors are often infiltrated by macrophages that generate an inflammatory gene signature predictive poor outcome, the initiation mechanism this pro-tumorigenic inflammation remains unknown. In our analysis clinical outcome-linked NB expression data, high TNFR1 was strongly correlated with event-free survival (5-year EFS...