A5087436846- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Bladder and Urothelial Cancer Treatments
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- 3D Printing in Biomedical Research
- Genetics, Aging, and Longevity in Model Organisms
- Neuroendocrine Tumor Research Advances
- Transgenic Plants and Applications
- Adrenal Hormones and Disorders
- Telomeres, Telomerase, and Senescence
- Circadian rhythm and melatonin
- Cancer-related gene regulation
- Prostate Cancer Treatment and Research
- Ferroptosis and cancer prognosis
- Virus-based gene therapy research
- Cervical Cancer and HPV Research
- Renal and related cancers
- Renal cell carcinoma treatment
- Cancer, Hypoxia, and Metabolism
- Heterotopic Ossification and Related Conditions
National Institutes of Health
2014-2024
National Cancer Institute
2014-2024
Frederick National Laboratory for Cancer Research
2021-2024
Leidos (United States)
2020-2024
Center for Cancer Research
2024
Leidos Biomedical Research Inc. (United States)
2020-2021
Trinity Washington University
2017
Small-cell lung cancer (SCLC) is an aggressive neuroendocrine cancer. Oncogenic MYC amplifications drive SCLC heterogeneity, but the genetic mechanisms of amplification and phenotypic plasticity, characterized by nonneuroendocrine cell states, are not known. Here, we integrate whole-genome sequencing, long-range optical mapping, single-cell DNA fluorescence in situ hybridization to find extrachromosomal (ecDNA) as a primary source oncogene driver fusions. ecDNAs bring proximity enhancer...
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,...
Kidney tumors lacking fumarate hydratase become aggressive due to a metabolic shift arising from altered mitochondrial DNA.
HPV35 has been found in only ∼2% of invasive cervical cancers (ICC) worldwide but up to 10% Sub-Saharan Africa, warranting further investigation and consideration impact on preventive strategies. We studied ethnicity, relation the known steps carcinogenesis, using multiple large epidemiologic studies U.S. internationally. Combining five studies, we measured positivity and, Northern California, observed type-specific population prevalence estimated 5-year risk developing precancer when...
Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire resembles mosaic of extrathymic including mucosal tuft cells. An additional mTEC produces chemokine CCL21, thereby attracting positively selected thymocytes from cortex to medulla. Both...
Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire resembles mosaic of extrathymic including mucosal tuft cells. An additional mTEC produces chemokine CCL21, thereby attracting positively selected thymocytes from cortex to medulla. Both...
CRISPR is revolutionizing the ability to do somatic gene editing in mice for purpose of creating new cancer models. Inactivation VHL tumor suppressor signature initiating event most common form kidney cancer, clear cell renal carcinoma (ccRCC). Such tumors are usually driven by excessive HIF2 activity that arises when product, pVHL, defective. Given pressing need a robust immunocompetent mouse model human ccRCC, we directly injected adenovirus-associated viruses (AAVs) encoding sgRNAs...
Human papillomavirus (HPV) type 31 (HPV31) is closely related to the most carcinogenic type, HPV16, but only accounts for 4% of cervical cancer cases worldwide. Viral genetic and epigenetic variations have been associated with carcinogenesis other high-risk HPV types, little known about HPV31. We sequenced 2093 HPV31 viral whole genomes from two large studies, one U.S. international. In addition, we investigated CpG methylation in a subset 175 samples. evaluated association...
Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire resembles mosaic of extrathymic including mucosal tuft cells. An additional mTEC produces chemokine CCL21, thereby attracting positively selected thymocytes from cortex to medulla. Both...
ABSTRACT Noroviruses are a major agent of acute gastroenteritis in humans, but host cell requirements for efficient replication vitro have not been established. We engineered human intestinal line (designated mCD300lf-hCaco2) expressing the murine norovirus (MNV) receptor, mouse CD300lf to become fully permissive MNV replication. To explore replicative machinery and response these cells, we performed single-cell RNA sequencing (scRNA-seq) transcriptomics analysis an infection over time....
<p>Amplicon design used for the targeted single-cell copy-number analysis. Normalized depth of MYC and MYCL amplicons in single-cells DMS-273 cell line are shown, as well comparison amplicon depths single cells between patient derived Adrenal gland (ecDNA+) Cerv.LN (HSR+) lines.</p>
Abstract Next generation sequencing (NGS) has identified frequently altered cancer genes in urologic cancers including bladder (BCa). We examined BCa tumors from 54 U.S. patients using exome NGS and targeted sequencing, compared these to 99 extensively characterized Chinese patient (Guo et al., 2013). are first show that telomerase (TERT) is the gene most by somatic sequence changes 37/54 (69%) of TERT also rare common germline variants 30/54 (56%) tumors. Most were novel (19/20) three...
Abstract The telomerase reverse transcriptase (TERT) gene encodes the catalytic subunit of enzyme telomerase, (aka telomere terminal transferase), which contains both protein and RNA subunits. TERT is a RNA-dependent polymerase increases length telomeres at ends each chromosome by adding TTAGGG repeats. uses as complementary primer to elongate telomeric G-rich repeat sequences in 5’ 3’ direction. essential active germ cells, stem primary tumors, immortalized cells acts maintain adequate...
Abstract Metastatic prostate cancer (mPCa) is a highly lethal disease and molecular markers identifying subtypes and/or therapeutic targets are needed. We sequenced the exomes of five metastatic tumors healthy kidney tissue from an index patient with castration resistant mPCa to identify lesions associated progression metastasis. A somatic missense TET2 alteration predicted be deleterious protein was observed at stage disease. in additional PCa cell lines detected alterations, frequent LOH,...
Abstract Next-generation sequencing (NGS) of urologic tumor genomes has identified frequently altered cancer genes. We recently examined the exomes bladder tumors (BCa) from 54 U.S. patients and 99 Chinese to identify novel, genes associated with clinical characteristics disease. Exome capture DNA normal urothelial tissue using probes for ~180,000 protein-coding exons microRNA loci; fragment libraries were sequenced on a HiSeq 2000 platform (Illumina); base calls paired-end, 100 bp reads...