A5090277365- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Chromatin Remodeling and Cancer
- RNA and protein synthesis mechanisms
- Chemical Reactions and Isotopes
- Renal and related cancers
- Angiogenesis and VEGF in Cancer
- Zebrafish Biomedical Research Applications
- Protein Degradation and Inhibitors
- Ferroptosis and cancer prognosis
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- PI3K/AKT/mTOR signaling in cancer
- Ubiquitin and proteasome pathways
- Kruppel-like factors research
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- RNA regulation and disease
- Cancer-related molecular mechanisms research
- Cancer, Lipids, and Metabolism
- Hedgehog Signaling Pathway Studies
Discovery Institute
2021-2024
Sanford Burnham Prebys Medical Discovery Institute
2021-2024
University of Minnesota
2001-2023
University of Massachusetts Chan Medical School
2023
Columbia University Irving Medical Center
2023
St. Jude Children's Research Hospital
2013-2020
University of Minnesota Medical Center
2013-2015
University of Connecticut
2013
ID Genomics (United States)
2003-2010
Cancer Genetics (United States)
2010
Morpholino phosphorodiamidate antisense oligonucleotides (MOs) and short interfering RNAs (siRNAs) are commonly used platforms to study gene function by sequence-specific knockdown. Both technologies, however, can elicit undesirable off-target effects. We have several model genes these effects in detail the zebrafish, Danio rerio. Using zebrafish embryo as a template, correct mistargeting readily discernible through direct comparison of MO-injected animals with well-studied mutants. show...
Angiogenesis is a fundamental vertebrate developmental process that requires signalling by the secreted protein vascular endothelial growth factor-A ( VEGF-A ). functions in development of embryonic structures, during tissue remodelling and for tumour-induced vasculature. The study role normal has been significantly complicated dominant, haplo-insufficient nature -targeted mutations mice. We have used morpholino-based targeted gene knock-down technology to generate zebrafish morphant loss...
Endothelial tubulogenesis is a crucial step in the formation of functional blood vessels during angiogenesis and vasculogenesis. Here, we use vivo imaging living zebrafish embryos expressing fluorescent fusion proteins β-Actin, α-Catenin, ERM family member Moesin1 (Moesin a), to define novel cord hollowing process that occurs initial stages intersegmental (ISVs) embryo. We show primary lumen elongates along cell junctions between at least two endothelial cells embryonic angiogenesis....
Abstract Spontaneous mouse models of cancer show promise to more accurately recapitulate human disease and predict clinical efficacy. Transgenic mice or viral vectors have been required generate spontaneous glioma, a lethal brain tumor, because nonviral gene transfer is typically transient. To overcome this constraint, we used the Sleeping Beauty transposable element achieve chromosomal integration oncogenes into endogenous cells immunocompetent mice. Genetically engineered, tumors were...
Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution drug resistance and poor outcomes. Applying computational methods for the detection reconstruction ecDNA across a retrospective cohort 481 medulloblastoma from 465 patients, we identify circular 82 patients (18%). Patients with ecDNA-positive were more than twice as likely to relapse three times die within 5 years diagnosis. A subset harbored multiple lineages, each...
Abstract We have identified the zebrafish homologue of VE‐cadherin and documented its expression in developing vascular system. The gene is specifically expressed endothelial cell lineage beginning with differentiation migration angioblasts persists throughout vasculogenesis, angiogenesis, endocardium development. Staining embryos by whole‐mount situ hybridization probe provides a method to screen for defects. To illustrate this utility, we used demonstrate conservation growth factor‐A...
Abstract Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain with limited effective therapies. Using Sleeping Beauty (SB) transposon mutagenesis, we identified novel genetic drivers of medulloblastoma CNS-PNET. Cross-species gene expression analyses classified SB-driven into distinct CNS-PNET subgroups, indicating they resemble human Sonic hedgehog group 3 4 CNS neuroblastoma FOXR2 activation. This represents the...
Understanding the functional role(s) of more than 20,000 proteins vertebrate genome is a major next step in post-genome era. The approximately 4,000 co-translationally translocated (CTT) - representing secretome are important for such vertebrate-critical processes as organogenesis. However, most these genes currently unknown.We identified 585 putative full-length zebrafish CTT using cross-species genomic and EST-based comparative sequence analyses. We further investigated 150 (Figure 1)...
The Sleeping Beauty (SB) transposon system has been used as an insertional mutagenesis tool to identify novel cancer genes. To glioma-associated genes, we evaluated tumor formation in the brain tissue from 117 transgenic mice that had undergone constitutive SB-mediated transposition. Upon analysis, 21 samples (18%) contained neoplastic with features of high-grade astrocytomas. These tumors expressed glial markers and were histologically similar human glioma. Genomic DNA SB-induced...
Abstract Motivation The traditional reads per million normalization method is inappropriate for the evaluation of ChIP-seq data when treatments or mutations have global effects. Changes in levels histone modifications can be detected with exogenous reference spike-in controls. However, most studies overlook that must corrected spike-in. A retrospectively renormalizes datasets without lacking. Results ChIPseqSpikeInFree a novel to effectively determine scaling factors samples across various...
Previous studies conducted in our laboratory showed that transgenic medaka expressing cecropin B transgenes exhibited resistant characteristic to fish bacterial pathogens, Pseudomonas fluorescens and Vibrio anguillarum. To confirm whether antimicrobial peptide gene will also exhibit anti-bacterial anti-viral characteristics aquaculture important species, we produced rainbow trout P1 or a synthetic analog, CF-17, transgene by sperm-mediated transfer method. About 30 % of recovered from...
The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in form response to evolutionary pressures is incompletely understood. We molecularly functionally characterized one member an evolutionarily dynamic family, plac8 onzin related protein 1 (ponzr1), the zebrafish. ponzr1 mRNA expressed early developing...
Abstract Deregulation of neuroblastoma-derived myc (N-myc) is a leading cause malignant brain tumors in children. To target N-myc-driven medulloblastoma, most research has focused on identifying genomic alterations or the analysis medulloblastoma transcriptome. Here, we have broadly characterized translatome and shown that N-myc unexpectedly drives selective translation transcripts promote protein homeostasis. Cancer cells are constantly exposed to proteotoxic stress associated with...
Morpholino phosphorodiamidate antisense oligonucleotides (MOs) and short interfering RNAs (siRNAs) are commonly used platforms to study gene function by sequence-specific knockdown. Both technologies, however, can elicit undesirable off-target effects. We have several model genes these effects in detail the zebrafish, Danio rerio. Using zebrafish embryo as a template, correct mistargeting readily discernible through direct comparison of MO-injected animals with well-studied mutants. show...
Loss of the tumor suppressor gene PTEN exerts diverse outcomes on cancer in different developmental contexts. To gain insight into effect its loss brain, we conditionally inactivated murine Pten neonatal neural stem/progenitor cells. inactivation created an abnormal perivascular proliferative niche cerebellum that persisted adult animals but did not progress to malignancy. Proliferating cells showed undifferentiated morphology and expressed progenitor marker Nestin Math1, a committed granule...
SUMMARY Extrachromosomal circular DNA (ecDNA) is an important driver of aggressive tumor growth, promoting high oncogene copy number, intratumoral heterogeneity, accelerated evolution drug resistance, enhancer rewiring, and poor outcome. ecDNA has been reported in medulloblastoma (MB), the most common malignant pediatric brain tumor, but landscape its association with specific MB subgroups, impact on potential clinical implications, are not known. We assembled a retrospective cohort 468...
Achieving adequate exposure of the free therapeutic agent at target is a critical determinant efficacious chemotherapy. With this in mind, major challenge developing therapies for central nervous system (CNS) tumors to overcome barriers delivery, including blood-brain barrier (BBB). Panobinostat nonselective pan–histone deacetylase inhibitor that being tested preclinical and clinical studies, treatment pediatric medulloblastoma, which has propensity leptomeningeal spread diffuse midline...