A5006889551- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Chronic Lymphocytic Leukemia Research
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Cancer-related molecular mechanisms research
- Acute Lymphoblastic Leukemia research
- Molecular Biology Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Lung Cancer Research Studies
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Cancer, Stress, Anesthesia, and Immune Response
- RNA modifications and cancer
- DNA and Nucleic Acid Chemistry
- Prostate Cancer Treatment and Research
- Cardiac electrophysiology and arrhythmias
- Pancreatic function and diabetes
- Genetics, Bioinformatics, and Biomedical Research
- Nutrition, Genetics, and Disease
- Skin and Cellular Biology Research
- Cancer Cells and Metastasis
ID Genomics (United States)
2018-2022
Genomics (United Kingdom)
2021
Scripps Research Institute
2013-2018
Scripps Health
2017-2018
Scripps Clinic
2012
Abstract Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort ( n = 64) comparison with non-cancer 243). Differential hydroxymethylation found thousands genes, most significantly genes related to pancreas development or function GATA4 , GATA6 PROX1 ONECUT1 MEIS2 ), and pathogenesis...
Diagnosis of monogenic as well atypical forms diabetes mellitus has important clinical implications for their specific diagnosis, prognosis, and targeted treatment. Single gene mutations that affect beta-cell function represent 1–2% all cases diabetes. However, phenotypic heterogeneity lack family history can limit the diagnosis Next-generation sequencing technologies provide an excellent opportunity to screen large numbers individuals with a in disease-associated genes. We utilized approach...
Analysis of DNA methylation is a valuable tool to understand disease progression and increasingly being used create diagnostic prognostic clinical biomarkers. While conversion cytosine 5-methylcytosine (5mC) commonly results in transcriptional repression, further 5-hydroxymethylcytosine (5hmC) associated with activation. Here we perform the first study integrating whole-genome 5hmC DNA, 5mC, transcriptome sequencing samples benign, localized, advanced prostate cancer. shown mark activation...
Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare common genetic environmental determinants. To identify variants associated AN, we pursued a series of sequencing genotyping studies focusing on the coding regions upstream sequence 152 candidate genes in total 1205 AN cases 1948 controls. We identified individual variant associations Estrogen Receptor-ß (ESR2) gene, as well set Epoxide Hydrolase 2 (EPHX2) an initial...
The conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is a key step in DNA demethylation that mediated by ten-eleven translocation (TET) enzymes, which require ascorbate/vitamin C. Here, we report the 5hmC landscape normal hematopoiesis and identify cell type-specific profiles associated with active transcription chromatin accessibility hematopoietic regulators. We utilized CRISPR/Cas9 model TET2 loss-of-function mutations primary human stem progenitor cells (HSPC)....
Background Treatment with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) can yield durable antitumor responses, yet not all patients respond to ICIs. Current approaches select who may benefit from anti-PD-1 treatment are insufficient. 5-hydroxymethylation (5hmC) analysis of plasma-derived cell-free DNA (cfDNA) presents a novel non-invasive approach for identification therapy response biomarkers which tackle challenges associated tumor biopsies such as heterogeneity...
The Scripps Molecular Autopsy (MA) study seeks to incorporate genetic testing into the postmortem examination of cases sudden death in young (< 45 years old). Here we describe results from first two study, which consisted whole exome sequencing (WES) a cohort 50 predominantly San Diego County. Apart individual description cases, analyzed data at cohort-level, brought new perspectives on causes death. We investigated advantages and disadvantages using WES compared gene panel for cardiac...
PurposeNail-Patella syndrome is a dominantly inherited genetic disorder characterized by abnormalities of the nails, knees, elbows, and pelvis. Nail are most constant feature Nail-Patella syndrome. Pathogenic mutations in single gene, LMX1B, mesenchymal determinant dorsal-ventral patterning, explain approximately 95% cases. However, 5% cases remain unexplained.MethodsHere, we present exome sequencing analysis four generations family with Nail-Patella-like (nail dysplasia some features...
ABSTRACT Our study employed the detection of 5-hydroxymethyl cytosine (5hmC) profiles on cell free DNA (cfDNA) from plasma cancer patients using a novel enrichment technology coupled with sequencing and machine learning based classification method. These methods were develo i ped to detect presence disease in control subjects. Cancer patient cfDNA cohorts accrued multiple sites consisting 48 breast, 55 lung, 32 prostate 53 pancreatic In addition, cohort 180 subjects (non-cancer) was match...
Abstract Background: Treatment with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) can yield durable anti-tumor responses, yet not all patients respond to ICIs. Current approaches select who may benefit from anti-PD-1 treatment are insufficient. 5-hydroxymethylation (5hmC) analysis of plasma-derived cell free DNA (cfDNA) presents a novel non-invasive approach for identification therapy response biomarkers which tackle challenges associated tumor biopsies such as...
<h3>Background</h3> Immune checkpoint inhibitors targeting programmed death-1 (PD-1) are among commonly used treatments for non-small cell lung cancer (NSCLC), but not all patients respond to anti-PD-1. The definition of biomarkers identify responders from non-responders anti-PD-1 treatment using liquid biopsy is an area active research.<sup>1</sup> Multiple types, including tumor and immune cells found when present, contribute the complexity plasma cell-free DNA (cfDNA).<sup>2</sup>...
Abstract Background: Epigenomic changes via the measurement of 5-hydroxymethylation cytosine (5hmC) in DNA have been shown to enable detection a variety cancers including pancreatic and ovarian cancer plasma-derived cell-free (cfDNA). Here, we investigated whether blood-based 5hmC profiling genomic (gDNA) derived from cells buffy coat (BC) possess signals that breast, colorectal lung cancers. Method: Blood samples collected Streck tubes patients or non-cancer controls were processed obtain...
Abstract Pancreatic cancers are typically diagnosed at late stage where disease prognosis is poor as exemplified by a 5-year survival rate of 8.2%. Earlier diagnosis would be beneficial enabling surgical resection or earlier application therapeutic regimens. We investigated the detection pancreatic ductal adenocarcinoma (PDAC) in non-invasive manner interrogating changes 5-hydroxymethylation cytosine status (5hmC) circulating cell free DNA plasma PDAC cohort (n=51) comparison with non-cancer...
Abstract BACKGROUND Pancreatic cancer (PaC) has poor (10%) 5-year overall survival, largely due to predominant late-stage diagnosis. Patients with new-onset diabetes (NOD) are at a six-to eightfold increased risk for PaC. We developed pancreatic detection test the use in clinical setting that employs logistic regression model based on 5-hydroxymethylcytosine (5hmC) profiling of cell-free DNA (cfDNA). METHODS cfDNA was isolated from plasma 89 subjects PaC and 596 case-control non-cancer...
Pancreatic cancers are typically diagnosed at late stage where disease prognosis is poor as exemplified by a 5-year survival rate of 8.2%. Earlier diagnosis would be beneficial enabling surgical resection or earlier application therapeutic regimens. We investigated the detection pancreatic ductal adenocarcinoma (PDAC) in non-invasive manner interrogating changes 5-hydroxymethylated cytosines (5hmC) circulating cell free DNA plasma PDAC cohort (n=51) comparison with non-cancer (n=41). 5hmC...
Abstract Pancreatic cancers are typically diagnosed at late stage where disease prognosis is poor as exemplified by a 5-year survival rate of 8.2%. Earlier diagnosis would be beneficial enabling surgical resection or earlier application therapeutic regimens. We investigated the detection pancreatic ductal adenocarcinoma (PDAC) in non-invasive manner interrogating changes 5-hydroxymethylated cytosines (5hmC) circulating cell free DNA plasma PDAC cohort (n=51) comparison with non-cancer...
<div>Abstract<p>The conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is a key step in DNA demethylation that mediated by ten–eleven translocation (TET) enzymes, which require ascorbate/vitamin C. Here, we report the 5hmC landscape normal hematopoiesis and identify cell type–specific profiles associated with active transcription chromatin accessibility hematopoietic regulators. We utilized CRISPR/Cas9 model <i>TET2</i> loss-of-function mutations...
<div>Abstract<p>The conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is a key step in DNA demethylation that mediated by ten–eleven translocation (TET) enzymes, which require ascorbate/vitamin C. Here, we report the 5hmC landscape normal hematopoiesis and identify cell type–specific profiles associated with active transcription chromatin accessibility hematopoietic regulators. We utilized CRISPR/Cas9 model <i>TET2</i> loss-of-function mutations...
Supplementary Figure from The Cell Type–Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis <i>TET2</i>-Mutant Preleukemia
Supplementary Figure from The Cell Type–Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis <i>TET2</i>-Mutant Preleukemia