A5102788564- Epigenetics and DNA Methylation
- Neuroblastoma Research and Treatments
- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- Acute Lymphoblastic Leukemia research
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Alzheimer's disease research and treatments
- Chronic Myeloid Leukemia Treatments
- Dementia and Cognitive Impairment Research
- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- Chronic Lymphocytic Leukemia Research
- Telomeres, Telomerase, and Senescence
- Genetics and Neurodevelopmental Disorders
- Cancer Genomics and Diagnostics
- Hematopoietic Stem Cell Transplantation
- Genomics and Rare Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Computational Drug Discovery Methods
- RNA Research and Splicing
Centre for DNA Fingerprinting and Diagnostics
2024
AbbVie (United States)
2017-2024
AbbVie (Netherlands)
2024
Jacobs Douwe Egberts (Netherlands)
2024
University of Wisconsin–Madison
2004-2020
Madison Group (United States)
2020
University of Chicago
2009-2019
University of Chicago Medicine Comprehensive Cancer Center
2019
Cornell University
2010-2013
Northwestern University
2013
Somatic mutations in IDH1/IDH2 and TET2 result impaired TET2-mediated conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). The observation that WT1 inactivating anticorrelate with TET2/IDH1/IDH2 acute myeloid leukemia (AML) led us hypothesize may impact function. mutant AML patients have reduced 5hmC levels similar AML. These are characterized by convergent, site-specific alterations DNA hydroxymethylation, which drive differential gene expression more than promoter...
Although aberrant DNA methylation patterning is a hallmark of cancer, the relevance targeting methyltransferases (DNMT) remains unclear for most tumors. In diffuse large B-cell lymphoma (DLBCL) we observed that chemoresistance associated with programming. Prolonged exposure to low-dose DNMT inhibitors (DNMTI) reprogrammed chemoresistant cells become doxorubicin sensitive without major toxicity in vivo. Nine genes were recurrently hypermethylated DLBCL. Of these, SMAD1 was critical...
The ten-eleven-translocation 5-methylcytosine dioxygenase (TET) family of enzymes catalyzes the conversion (5-mC) to 5-hydroxymethylcytosine (5-hmC), a modified cytosine base that facilitates gene expression. Cells respond hypoxia by inducing transcriptional program regulated in part oxygen-dependent dioxygenases require Fe(II) and α-ketoglutarate. Given TET also these cofactors, we hypothesized TETs regulate hypoxia-induced program. Here, demonstrate increases global 5-hmC levels, with...
TET2 enzymatically converts 5-methyl-cytosine to 5-hydroxymethyl-cytosine, possibly leading loss of DNA methylation. mutations are common in myeloid leukemia and were proposed contribute leukemogenesis through To expand on this concept, we studied chronic myelomonocytic (CMML) samples. missense or nonsense detected 53% (16/30) patients. In contrast, only 1/30 patient had a mutation IDH1 IDH2, none them DNMT3A the sites most frequently mutated leukemia. Using bisulfite pyrosequencing, global...
Changes in DNA methylation are required for the formation of germinal centers (GCs), but mechanisms such changes poorly understood. Activation-induced cytidine deaminase (AID) has been recently implicated demethylation through its activity coupled with repair. We investigated epigenetic function AID vivo center B cells (GCBs) isolated from wild-type (WT) and AID-deficient (Aicda−/−) mice. determined that transit GC is associated marked locus-specific loss increased diversity, both which lost...
Hematopoietic stem cell differentiation involves the silencing of self-renewal genes and induction a specific transcriptional program. Identification multiple covalent cytosine modifications raises question how these derivatized bases influence commitment. Using replicative primary human hematopoietic stem/progenitor system, we demonstrate dynamic changes 5-hydroxymethylcytosine (5-hmC) during commitment to erythroid lineage. Genomic loci that maintain or gain 5-hmC density throughout...
Abstract Background Alzheimer’s disease (AD) is a chronic progressive neurodegenerative impacting an estimated 44 million adults worldwide. The causal pathology of AD (accumulation amyloid-beta and tau), precedes hallmark symptoms dementia by more than decade, necessitating development early diagnostic markers onset, particularly for new drugs that aim to modify processes. To evaluate differentially methylated positions (DMPs) as novel blood-based biomarkers AD, we used subset 653...
Abstract Background Identifying biomarkers associated with Alzheimer’s disease (AD) progression may enable patient enrichment and improve clinical trial designs. Epigenome-wide association studies have revealed correlations between DNA methylation at cytosine-phosphate-guanine (CpG) sites AD pathology diagnosis. Here, we report relationships peripheral blood profiles measured using Infinium® MethylationEPIC BeadChip in participants from the Disease Neuroimaging Initiative (ADNI) cohort....
TET2 enzymatically converts 5-methylcytosine to 5-hydroxymethylcytosine as well other covalently modified cytosines and its mutations are common in myeloid leukemia. However, the exact mechanism extent which affect DNA methylation remain question. Here, we report on methylomes wild-type (TET2-WT) mutant (TET2-MT) cases of chronic myelomonocytic leukemia (CMML). We analyzed 85,134 CpG sites [28,114 islands (CGI) 57,020 non-CpG (NCGI)]. do not explain genome-wide differences CMML, found few...
Abstract Background Limited understanding of the diversity variants in cystic fibrosis transmembrane conductance regulator ( CFTR ) gene across ancestries hampers efforts to advance molecular diagnosis (CF). The consequences pose a risk delayed diagnoses and subsequently worsened health outcomes for patients. Therefore, characterizing spectrum is critical revolutionizing CF. Methods We analyzed 454,727 UK Biobank (UKBB) whole-exome sequences characterize ancestries. Using PanUKBB...
5-hydroxymethylcytosine (5-hmC) is a recently discovered epigenetic modification that altered in cancers. Genome-wide assays for 5-hmC determination are needed as many of the techniques 5-methylcytosine (5-mC) determination, including methyl-sensitive restriction digestion and bisulfite sequencing cannot distinguish between 5-mC 5-hmC. Glycosylation residues by beta-glucosyl transferase (β-GT) can make CCGG insensitive to MspI. Restriction HpaII, MspI or after β-GT conversion, followed...
Epigenetic changes are among the most common alterations observed in cancer cells, yet mechanism by which cells acquire and maintain abnormal DNA methylation patterns is not understood. Cancer have an altered distribution of express aberrant methyltransferase 3B transcripts, encode truncated proteins, some lack COOH-terminal catalytic domain. To test if a DNMT3B isoform disrupts vivo, we constructed two lines transgenic mice expressing DNMT3B7, commonly found cells. DNMT3B7 exhibit embryonic...
INTRODUCTION: Genome-wide association studies (GWAS) have identified Bridging Integrator 1 (BIN1) as the second-most significant genetic risk factor for Alzheimer's disease (AD). We performed GWAS by proxy (GWAX) using UKBiobank and replicated this finding. However, mechanism which BIN1 impacts AD is largely unknown. METHODS: To address this, we first measured expression of isoforms in a human induced pluripotent stem cells (hiPSC) model further evaluated whether loci associated with Phase 2...
Abstract Background Analysis of cerebrospinal fluid (CSF) facilitates the understanding brain-specific molecular changes that may associate with disease progression. Proximity extension assays (PEA) have been deployed in several CSF studies, however validation assay and impact freeze-thaw cycles on protein signal has not documented. We sought to (1) validate PEA platform (2) evaluate effect detectability analytes platform. Results validated Next Generation Sequencing (NGS) readout report...