A5088872826- Epigenetics and DNA Methylation
- Advanced Radiotherapy Techniques
- Radiomics and Machine Learning in Medical Imaging
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- vaccines and immunoinformatics approaches
- Advanced X-ray and CT Imaging
- Advances in Oncology and Radiotherapy
- Cancer-related gene regulation
- Head and Neck Cancer Studies
- Radiation Therapy and Dosimetry
- Genetic Syndromes and Imprinting
- Lung Cancer Diagnosis and Treatment
- Birth, Development, and Health
- Genomics and Chromatin Dynamics
- Radiation Dose and Imaging
- Cancer-related molecular mechanisms research
- Artificial Intelligence in Healthcare and Education
- Cancer Diagnosis and Treatment
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- RNA Research and Splicing
- Prostate Cancer Treatment and Research
Oregon Health & Science University
2017-2025
VA Portland Health Care System
2017-2025
Oregon Medical Research Center
2021-2022
Orthopedic Specialty Hospital
2021-2022
Portland VA Medical Center
2017-2022
OHSU Knight Cancer Institute
2022
University of Portland
2022
University of Pennsylvania
2013-2020
United States Department of Veterans Affairs
2020
Creative Commons
2020
Individual genetic variation may help to explain different immune responses a virus across population. In particular, understanding how in HLA affect the course of COVID-19 could identify individuals at higher risk from disease. typing can be fast and inexpensive. Pairing with testing where feasible improve assessment severity viral disease Following development vaccine against SARS-CoV-2, that causes COVID-19, high-risk types prioritized for vaccination.
The distribution of cytosine methylation in 6.2 Mb the mouse genome was tested using cohybridization genomic representations from a methylation-sensitive restriction enzyme and its methylation-insensitive isoschizomer. This assay, termed HELP ( H paII tiny fragment E nrichment by L igation-mediated P CR), allows both intragenomic profiling intergenomic comparisons methylation. profile shows most to be contiguous methylated sequence with occasional clusters hypomethylated loci, usually but...
The normal aging process is a complex phenomenon associated with physiological alterations in the function of cells and organs over time. Although an attractive candidate for mediating transcriptional dysregulation, contribution epigenetic dysregulation to these progressive changes cellular physiology remains unclear. In this study, we employed genome-wide HpaII tiny fragment enrichment by ligation-mediated PCR assay define patterns cytosine methylation throughout rat genome luminometric...
Intrauterine growth restriction (IUGR) increases susceptibility to age-related diseases, including type 2 diabetes (T2DM), and is associated with permanent progressive changes in gene expression. Our study was designed test whether epigenomic dysregulation mediates the cellular memory of this intrauterine event. To hypothesis, we isolated pancreatic islets from control IUGR (induced by bilateral uterine artery ligation at day 18 fetal life) animals 7 weeks age. Using HELP (HpaII tiny...
Many genome-wide assays involve the generation of a subset (or representation) genome following restriction enzyme digestion. The use enzymes sensitive to cytosine methylation allows high-throughput analysis this epigenetic regulatory process. We show that dual-adapter approach us generate genomic representations includes fragments <200 bp in size, previously not possible when using standard single adapter. By expanding representation smaller HpaII or MspI, we increase by these isoschizomers...
Although a combination of genomic and epigenetic alterations are implicated in the multistep transformation normal squamous esophageal epithelium to Barrett esophagus, dysplasia, adenocarcinoma, combinatorial effect these changes is unknown. By integrating genome-wide DNA methylation, copy number, transcriptomic datasets obtained from endoscopic biopsies neoplastic progression within same individual, we uniquely able define molecular events associated esophagus. We find that previously...
Perturbations of the intrauterine environment can affect fetal development during critical periods plasticity, and increase susceptibility to a number age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late decades later. We hypothesized that this biological memory is mediated by permanent alterations epigenome in stem cell populations, focused our studies specifically on DNA methylation CD34+ hematopoietic progenitor cells from cord blood neonates with growth...
Background Checkpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published report showed that men with cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized addition of PD-1 these patients could a meaningful response. Methods...
Tumor mutational burden (TMB; the quantity of aberrant nucleotide sequences a given tumor may harbor) has been associated with response to immune checkpoint inhibitor therapy and is gaining broad acceptance as result. However, TMB harbors intrinsic variability across cancer types, its assessment interpretation are poorly standardized.Using standardized approach, we quantify robustness metric potential predictor immunotherapy survival among diverse cohort patients. We also explore additive...
ABSTRACT Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen [HLA] A, B, and C) may affect susceptibility to severity of severe acute respiratory syndrome 2 (SARS-CoV-2), virus responsible for coronavirus disease 2019 (COVID-19). We execute a comprehensive in silico analysis viral peptide-MHC binding affinity 145 HLA -A, -B, -C genotypes all SARS-CoV-2 peptides. further explore potential cross-protective immunity conferred by...
Mechanisms of therapeutic resistance and vulnerability evolve in metastatic cancers as tumor cells extrinsic microenvironmental influences change during treatment. To support the development methods for identifying these mechanisms individual people, here we present an omic multidimensional spatial (OMS) atlas generated from four serial biopsies with breast cancer 3.5 years therapy. This resource links detailed, longitudinal clinical metadata that includes treatment times doses, anatomic...
Abstract Cell-free RNA (cfRNA) in plasma reflects phenotypic alterations of both localized sites cancer and the systemic host response. Here we report that cfRNA sequencing enables discovery messenger (mRNA) biomarkers with tissue origin-specific to types precancerous conditions solid hematologic malignancies. To explore diagnostic potential total from blood, sequenced samples eight hepatocellular carcinoma (HCC) ten multiple myeloma (MM) patients, 12 patients their respective conditions, 20...
Abstract The superfamily of myosin proteins found in eukaryotic cells is known to contain at least 18 different classes. Members are classified based on the phylogenetic analysis head domains located amino terminus polypeptide. While relationships provide insights into functional relatedness myosins within and between families, evolutionary history not revealed by such studies. In order establish superfamily, we analyzed representation gene families a range organisms covering taxonomic...
Systemic steroids are commonly used to manage immune-related adverse events (irAEs), but it remains unclear whether they may undermine immune checkpoint inhibitor (ICI) therapy outcomes. Few studies have assessed the impact of steroid timing and its association with continuation or cessation ICI therapy.
Cytosines at cytosine-guanine (CG) dinucleotides are the near-exclusive target of DNA methyltransferases in mammalian genomes. Spontaneous deamination methylcytosine to thymine makes methylated cytosines unusually susceptible mutation and consequent depletion. The loci where CG remain relatively enriched, presumably due their unmethylated status during germ cell cycle, have been referred as CpG islands. Currently, islands solely defined by base compositional criteria, allowing annotation any...
The molecular heterogeneity of acute leukemias and other tumors constitutes a major obstacle towards understanding disease pathogenesis developing new targeted-therapies. Aberrant gene regulation is hallmark cancer plays central role in determining tumor phenotype. We predicted that integration different genome-wide epigenetic regulatory marks along with expression levels would provide greater power capturing biological differences between leukemia subtypes. Gene expression, cytosine...
Abstract Motivation: DNA cytosine methylation is an important epigenetic regulator, critical for mammalian development and the control of gene expression. Numerous techniques using either restriction enzyme or affinity-based approaches have been developed to interrogate status genome-wide, however these assays must be validated by a more quantitative approach, such as MALDI-TOF mass spectrometry bisulphite-converted (commercialized Sequenom's EpiTYPER assay MassArray system). Here, we...
Uncontrolled local growth is the cause of death in ∼ 30% patients with unresectable pancreatic cancers. The addition standard-dose radiotherapy to gemcitabine has been shown confer a modest survival benefit this population. Radiation dose escalation three-dimensional planning not feasible, but high-dose intensity-modulated radiation therapy (IMRT) improve control. Still, dose-escalation remains limited by gastrointestinal toxicity. In study, authors investigate potential use double...
Epigenetic factors play a role in the expression of virulence traits Apicomplexa. Apicomplexan genomes encode putative DNA cytosine methylation enzymes. To assess presence Toxoplasma gondii and Cryptosporidium parvum DNA, we used mass spectrometry analysis confirmed that these organisms lack detectable methylcytosine their DNA.