A5022364498- Glioma Diagnosis and Treatment
- Microtubule and mitosis dynamics
- Mathematical Biology Tumor Growth
- Cancer Mechanisms and Therapy
- Melanoma and MAPK Pathways
- Computational Drug Discovery Methods
- Herpesvirus Infections and Treatments
- Neuroblastoma Research and Treatments
- Single-cell and spatial transcriptomics
- Nanoplatforms for cancer theranostics
- Cytomegalovirus and herpesvirus research
- Protein Degradation and Inhibitors
- HIV Research and Treatment
- Cancer Genomics and Diagnostics
- HIV/AIDS Research and Interventions
- Viral-associated cancers and disorders
- Cancer, Hypoxia, and Metabolism
- HIV/AIDS drug development and treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Colorectal Cancer Treatments and Studies
- Cancer Treatment and Pharmacology
- interferon and immune responses
- Immune Response and Inflammation
Morgan Adams Foundation
2017-2025
University of Colorado Denver
2016-2025
Children's Hospital Colorado
2020-2025
University of Colorado Anschutz Medical Campus
2018-2024
Creighton University
2012-2014
CHI Health Creighton University Medical Center - Bergan Mercy
2013
Stroke-induced cerebral ischemia is a major cause of death and disability. The disruption blood flow results in neuronal glial cell leading to brain injury. Reperfusion restores oxygen the affected tissue, but can also damage through an enhanced oxidative stress inflammatory response. This study examines mitochondrial transfer from MSC neurons role it plays preservation after oxidant We observed mitochondria mouse vitro following hydrogen peroxide exposure. was dependent on cell-to-cell...
Abstract Background Medulloblastoma (MB) is a heterogeneous disease in which neoplastic cells and associated immune contribute to progression. We aimed determine the influence of cell diversity on MB biology patient samples animal models. Methods To better characterize cellular heterogeneity we used single-cell RNA sequencing, immunohistochemistry, deconvolution transcriptomic data profile populations models across childhood subgroups. Results Neoplastic cluster primarily according...
The use of combination antiretroviral nanoparticles (cART NPs) was investigated as a novel treatment approach for the inhibition HIV-1 replication. We developed biodegradable polymer, poly-(dl-lactide-co-glycolic acid; PLGA) containing efavirenz (EFV) and boosted lopinavir (lopinavir/ritonavir; LPV/r) by high-pressure homogenization method. method resulted in >79% drug entrapment efficiency each three drugs. average size cART NPs 138.3±55.4 nm measured dynamic light scanning, confirmed...
A desperate need for novel therapies in pediatric ependymoma (EPN) exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN have significant infiltration of immune cells, which correlates with outcome. Immune checkpoint inhibitors provide an avenue new treatments. This study characterizes tumor-infiltrating cells aims at predicting candidates clinical trials using targeting PD-L1/PD-1 (programmed death ligand 1/programmed 1).The transcriptomic profiles the primary cohort...
Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and sequencing on 32 RIG tumors in vitro drug screen two cell lines. report that based methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, Ch. 13q 14q loss; focal PDGFRA CDK4 gain CDKN2A BCOR loss. Transcriptomically,...
Diffuse midline glioma (DMG) and Glioblastoma are malignant brain tumors in pediatric adult patients. The current standard-of-care treatment for DMG is radiotherapy (RT), whereas GBM includes surgery, followed by RT chemotherapy. Although known to modulate immune responses cancer enhance the effectiveness of myeloid checkpoint blockade, downstream macrophage differential phagocytosis induction remain poorly understood. This study examined macrophage-mediated caused either RT, anti-CD47 or...
Abstract Cardiovascular disease (CVD) is the most common cause of death in patients with native and post-transplant chronic kidney (CKD). To identify new biomarkers vascular injury inflammation, we analyzed proteome plasma circulating extracellular vesicles (EVs) CKD utilizing an aptamer-based assay. Proteins angiogenesis were significantly higher versus healthy controls. Ingenuity pathway analysis (IPA) indicated Ephrin receptor signaling, serine biosynthesis, transforming growth factor-β...
Abstract Background Ependymoma (EPN) posterior fossa group A (PFA) has the highest rate of recurrence and worst prognosis all EPN molecular groups. At relapse, it is typically incurable even with re-resection re-irradiation. The biology recurrent PFA remains largely unknown; however, increasing use surgery at first now provided access to clinical samples facilitate a better understanding this. Methods In this large longitudinal international multicenter study, we examined matched primary...
Abstract Purpose: Tumor relapse after radiotherapy is a major hurdle in treating pediatric H3K27M-mutant diffuse midline gliomas (DMG). Radiotherapy-induced stress increases association of BCL2 family proteins with BH3 pro-apoptotic activators preventing apoptosis. We hypothesized that inhibition radiotherapy-induced clinically relevant inhibitor, venetoclax, will block activity leading to increased has never been implicated DMG as resistant mechanism. Experimental Design: performed an...
The cytokine Interferon-γ (IFN-γ) exerts powerful immunoregulatory effects on the adaptive immune system and also enhances functions of neutrophil (PMN). clinical use IFN-γ has been driven by finding that its administration to patients with chronic granulomatous disease (CGD) results in decreased incidence severity infections. However, no effect characteristic defect CGD, inability convert oxygen microbicidal metabolites including superoxide anion (O 2 - ) during phagocytosis associated...
Inflammation has been identified as a hallmark of high-risk Group A (GpA) ependymoma (EPN). Chronic interleukin (IL)-6 secretion from GpA tumors drives an immune suppressive phenotype by polarizing infiltrating monocytes. This study determines the mechanism which IL-6 is dysregulated in EPN.Twenty pediatric and 21 B (GpB) EPN had gene set enrichment analysis for MSigDB Hallmark sets performed. Protein RNA patients cell lines were used to validate transcriptomic findings. 811 928 vitro...
Treatment for pediatric posterior fossa group A (PFA) ependymoma with gain of chromosome 1q (1q+) has not improved over the past decade owing partially to lack clinically relevant models. We described first 2 1q+ PFA cell lines, which have significantly enhanced our understanding tumor biology and provided a tool identify specific therapies. However, lines do accurately replicate microenvironment. Our present goal is establish patient-derived xenograft (PDX) mouse models.Disaggregated tumors...
ABSTRACT Regulation of gene transcription in varicella-zoster virus (VZV), a ubiquitous human neurotropic alphaherpesvirus, requires coordinated binding multiple host and proteins onto specific regions the genome. Chromatin immunoprecipitation (ChIP) is widely used to determine location along genomic region. Since size range sheared DNA fragments governs limit accurate protein localization, particularly for compact herpesvirus genomes, we quantitative PCR (qPCR)-based assay efficiency VZV...
Atypical teratoid/thabdoid tumor (AT/RT) remains a difficult-to-treat with 5-year overall survival rate of 15%-45%. Proteasome inhibition has recently been opened as an avenue for cancer treatment the FDA approval bortezomib (BTZ) in 2003 and carfilzomib (CFZ) 2012. The aim this study was to identify characterize pre-approved targeted therapy potential clinical trials AT/RT.We performed drug screen using panel 134 FDA-approved drugs 3 AT/RT cell lines. Follow-on vitro studies used 6 lines...
Abstract Brain tumors are the most common solid tumor in children, and low-grade gliomas (LGGs) childhood brain tumor. Here, we report on 3 patients with LGG harboring previously unreported or rarely reported RAF fusions: FYCO1-RAF1, CTTNBP2-BRAF, SLC44A1-BRAF. We hypothesized that these would show molecular similarity to canonical KIAA1549-BRAF fusion is widely seen alteration pilocytic astrocytoma (PA), pediatric variant, this include mitogen-activated protein kinase (MAPK) pathway...
ABSTRACT The neurotropic herpesvirus varicella-zoster virus (VZV) establishes a lifelong latent infection in humans following primary infection. low abundance of VZV nucleic acids human neurons has hindered an understanding the mechanisms that regulate viral gene transcription during latency. To overcome this critical barrier, we optimized targeted capture protocol to enrich DNA and cDNA prior whole-genome/transcriptome sequence analysis. Since genome is remarkably stable, it was surprising...
Diffuse midline gliomas (DMGs) are incurable pediatric tumors with extraordinarily limited treatment options. Decades of clinical trials combining conventional chemotherapies radiation therapy have failed to improve these outcomes, demonstrating the need identify and validate druggable biologic targets within this disease. NTRK1/2/3 fusions found in a broad range cancers, including high-grade subset DMGs. Phase 1/2 studies TRK inhibitors demonstrated good tolerability, effective CNS...
Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis DNA repair genes may identify children treated with radiation therapy for tumors at increased risk treatment toxicity and adverse neurocognitive outcomes.
SUMMARY Virus infection is frequently characterized using bulk cell populations. How these findings correspond to in individual cells remains unclear. Here, we integrate high-dimensional single-cell approaches quantify viral and host RNA protein expression signatures de novo with a well-characterized model gammaherpesvirus. While infected demonstrated genome-wide transcription, revealed pronounced variation gene expression, only 9 of 80 annotated open reading frames uniformly expressed all...