James C. Costello
A5035378993- Bladder and Urothelial Cancer Treatments
- Epigenetics and DNA Methylation
- Ferroptosis and cancer prognosis
- Prostate Cancer Treatment and Research
- Cancer Cells and Metastasis
- Peptidase Inhibition and Analysis
- Pancreatic and Hepatic Oncology Research
- RNA modifications and cancer
- Cancer Research and Treatments
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Bioinformatics and Genomic Networks
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Lipids, and Metabolism
- Computational Drug Discovery Methods
- Genomics and Phylogenetic Studies
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Telomeres, Telomerase, and Senescence
- Metal complexes synthesis and properties
- Brain Metastases and Treatment
- Gastric Cancer Management and Outcomes
University of Colorado Cancer Center
2016-2025
University of Colorado Anschutz Medical Campus
2016-2025
University of Colorado Denver
2016-2025
Boston University
2011-2020
Bioscience Research
2018
University of Utah
2017
University of Turku
2017
Åbo Akademi University
2017
The University of Texas Southwestern Medical Center
2017
Turku Centre for Biotechnology
2017
Mitochondrial dysfunction and oxidative damage induced by bactericidal antibiotics in mammalian cells may be alleviated an antioxidant or prevented preferential use of bacteriostatic antibiotics.
Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front resistance as well relapse following initial response demonstrates the need for a deeper understanding mechanisms. In present study, we report that to venetoclax +azacitidine AML correlate closely developmental stage, where phenotypically primitive is sensitive, but monocytic more resistant. Mechanistically, resistant has distinct...
A community computational challenge generates algorithms to predict activity of drug combinations. Recent therapeutic successes have renewed interest in combinations, but experimental screening approaches are costly and often identify only small numbers synergistic The DREAM consortium launched an open foster the development silico methods computationally rank 91 compound pairs, from most antagonistic, based on gene-expression profiles human B cells treated with individual compounds at...
The downstream effects of false promotion Special DNA sequences at the ends chromosomes, called telomeres, are replenished by a dedicated enzyme telomerase. A subset human tumors harbors mutations in promoter region TERT gene, which codes for subunit Borah et al. explored cells derived from urothelial (urinary tract) cancers. were associated with aberrantly high levels mRNA, protein and telomerase activity, longer telomeres. small study clinical samples suggested that mRNA may be marker more...
Abstract Motivation Gene Set Enrichment Analysis (GSEA) is routinely used to analyze and interpret coordinate pathway-level changes in transcriptomics experiments. For an experiment where less than seven samples per condition are compared, GSEA employs a competitive null hypothesis test significance. A gene set enrichment score tested against distribution of scores generated from permuted sets, genes randomly selected the input experiment. Looking across variety biological conditions,...
Rapid and inexpensive sequencing technologies are making it possible to collect whole genome sequence data on multiple individuals from a population. This type of can be used quickly identify genes that control important ecological evolutionary phenotypes by finding the targets adaptive natural selection, we therefore refer such approaches as "reverse ecology." To quantify power gained in detecting positive selection using population genomic data, compare three statistical methods for...
Abstract Immunotherapies targeting the PD-1/PD-L1 axis are now a mainstay in clinical management of multiple cancer types, however, many tumors still fail to respond. CCL2 is highly expressed various types and has been shown be associated with poor prognosis. Inhibition or blockade CCL2/CCR2 signaling thus an area interest for therapy. Here we show across murine tumor metastasis models that CCR2 antagonism combination anti-PD-1 therapy leads sensitization enhanced response over monotherapy....
In vivo–based functional genomic screen identifies DDR2 as an important determinant of efficacy anti–PD-1 immunotherapy.
Trisomy 21 (T21) causes Down syndrome (DS), affecting immune and neurological function by ill-defined mechanisms. Here we report a large metabolomics study of plasma cerebrospinal fluid, showing in independent cohorts that people with DS produce elevated levels kynurenine quinolinic acid, two tryptophan catabolites potent immunosuppressive neurotoxic properties, respectively. Immune cells overexpress IDO1, the rate-limiting enzyme pathway (KP) known interferon (IFN)-stimulated gene....
Genetic analysis of bladder cancer has revealed a number frequently altered genes, including frequent alterations the telomerase (TERT) gene promoter, although few genes have been functionally evaluated. Our objective is to characterize observed by exome sequencing and TERT examine functional relevance histone lysine (K)-specific demethylase 6A (KDM6A/UTX), mutated demethylase, in cancer.We analyzed samples from 54 U.S. patients targeted confirmed somatic variants using normal tissue same...
The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes 25 bladder cancer (BCa) compared mutations, copy number alterations (CNAs), gene expression drug response BCa patient profiles in Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs APOBEC-family cytosine deaminases similar signatures derived from somatic muscle-invasive (MI) tumors,...
Identification of pregnancies at risk preterm birth (PTB), the leading cause newborn deaths, remains challenging given syndromic nature disease. We report a longitudinal multi-omics study coupled with DREAM challenge to develop predictive models PTB. The findings indicate that whole-blood gene expression predicts ultrasound-based gestational ages in normal and complicated (r = 0.83) and, using data collected before 37 weeks gestation, also delivery date both 0.86) those spontaneous 0.75)....
The recommended treatment for patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) instillations. However, only 50% of benefit from this therapy. If progression to advanced disease occurs, then must undergo a radical cystectomy risks substantial morbidity and poor clinical outcome. Identifying tumors unlikely respond BCG can translate into alternative treatments, such as early cystectomy, targeted...
Abstract T and B lymphocytes are developmentally functionally related cells of the immune system, representing two major branches adaptive immunity. Although originating from a common precursor, they play very different roles: contribute to drive cell-mediated immunity, whereas secrete Abs. Because their functional importance well-characterized differentiation pathways, ideal cell types with which understand how differences encoded at transcriptional level. there has been great deal interest...
Hematopoietic stem cells (HSCs) maintain blood homeostasis and are the functional units of bone marrow transplantation. To improve molecular understanding HSCs their proximal progenitors, we performed transcriptome analysis within context ImmGen Consortium data set. Gene sets that define steady-state mobilized HSCs, as well hematopoietic progenitor (HSPCs), were determined. Genes involved in transcriptional regulation, including a group putative repressors, identified multipotent progenitors...
Abstract Prostate cancer subtypes are poorly defined and functional validation of drivers ETS rearrangement–negative prostate has not been conducted. Here, we identified an ETS− subtype aggressive (ERG−MAP3K7delCHD1del) used a novel developmental model cell line xenograft to show that cosuppression MAP3K7 CHD1 expression promotes disease. Analyses publicly available datasets revealed were significantly codeleted in 10% 20% localized tumors combined loss correlated with poor disease-free...
Alternative splicing (AS) allows increased diversity and orthogonal regulation of the transcriptional products mammalian genomes. To assess distribution variation alternative across cell lineages immune system, we comprehensively analyzed RNA sequencing microarray data generated by Immunological Genome Project Consortium. AS is pervasive: 60% genes showed frequent isoforms in T or B lymphocytes, with 7,599 previously unreported isoforms. Distinct specificity was observed, differential exon...