A5009275849- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- RNA modifications and cancer
- Acute Lymphoblastic Leukemia research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Pluripotent Stem Cells Research
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Hemoglobinopathies and Related Disorders
- Genomics and Chromatin Dynamics
- Chronic Myeloid Leukemia Treatments
- Immune cells in cancer
- RNA Research and Splicing
- Chronic Lymphocytic Leukemia Research
- Renal and related cancers
- RNA Interference and Gene Delivery
- Glioma Diagnosis and Treatment
- Phytase and its Applications
- Genetic Syndromes and Imprinting
- Tuberculosis Research and Epidemiology
- Botanical Research and Applications
- Hematopoietic Stem Cell Transplantation
University of Miami
2017-2025
Sylvester Comprehensive Cancer Center
2017-2025
George Washington University
2025
Ocean Medical Center
2025
University Medical Center
2025
Fundación Huésped
2024
Cornell University
2008-2023
Albert Einstein College of Medicine
2005-2023
Johns Hopkins Medicine
2022
Sidney Kimmel Comprehensive Cancer Center
2014-2022
Acute myeloid leukemia (AML) is a heterogeneous disease with respect to presentation and clinical outcome. The prognostic value of recently identified somatic mutations has not been systematically evaluated in phase 3 trial treatment for AML.We performed mutational analysis 18 genes 398 patients younger than 60 years age who had AML were randomly assigned receive induction therapy high-dose or standard-dose daunorubicin. We validated our findings an independent set 104 patients.We at least...
DNA methylation is a chemical modification of cytosine bases that pivotal for gene regulation, cellular specification and cancer development. Here, we describe an R package, methylKit, rapidly analyzes genome-wide epigenetic profiles from high-throughput hydroxymethylation sequencing experiments. methylKit includes functions clustering, sample quality visualization, differential analysis annotation features, thus automating simplifying many the steps discerning statistically significant or...
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...
We have developed an enhanced form of reduced representation bisulfite sequencing with extended genomic coverage, which resulted in greater capture DNA methylation information regions lying outside traditional CpG islands. Applying this method to primary human bone marrow specimens from patients Acute Myelogeneous Leukemia (AML), we demonstrated that genetically distinct AML subtypes display diametrically opposed patterns. As compared normal controls, observed widespread hypermethylation IDH...
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 azacitidine (AZA) improves survival in patients with high-risk myelodysplastic syndrome, the overall response remains approximately 50%. Entinostat is a histone deacetylase inhibitor that has been combined AZA significant clinical activity previous phase I dose finding study.Open label II randomized trial comparing 50 mg/m(2)/d given for 10 days ± entinostat 4 day 3 and 10. All subtypes of myelodysplasia, chronic myelomonocytic leukemia, acute myeloid leukemia myelodysplasia-related...
Mutant IDH1 coexpressed with inactivating TP53 and ATRX mutations in glioma enhances DNA repair, causing resistance to genotoxic therapies.
The cytidine analogues azacytidine and 5-aza-2'-deoxycytidine (decitabine) are commonly used to treat myelodysplastic syndromes, with or without a myeloproliferative component. It remains unclear whether the response these hypomethylating agents results from cytotoxic an epigenetic effect. In this study, we address question in chronic myelomonocytic leukaemia. We describe comprehensive analysis of mutational landscape tumours, combining whole-exome whole-genome sequencing. identify average...
Motivation: DNA methylation plays critical roles in gene regulation and cellular specification without altering sequences. The wide application of reduced representation bisulfite sequencing (RRBS) whole genome (bis-seq) opens the door to study at single CpG site resolution. One challenging question is how best test for significant differences between groups biological samples order minimize false positive findings. Results: We present a statistical analysis package, methylSig, analyse...
Abstract Aging is associated with functional decline of hematopoietic stem cells (HSC) as well an increased risk myeloid malignancies. We performed integrative characterization epigenomic and transcriptomic changes, including single-cell RNA sequencing, during normal human aging. Lineage−CD34+CD38− [HSC-enriched (HSCe)] undergo age-associated epigenetic reprogramming consisting redistribution DNA methylation reductions in H3K27ac, H3K4me1, H3K4me3. This aged HSCe globally targets...
The class II Histone deacetylase (HDAC), HDAC4, is expressed in a tissue-specific manner, and it represses differentiation of specific cell types. We demonstrate here that HDAC4 the proliferative zone small intestine colon its expression down-regulated during intestinal vivo vitro. Subcellular localization studies demonstrated was predominantly nuclear proliferating HCT116 cells relocalized to cytoplasm after cycle arrest. Down-regulating by interfering RNA (siRNA) induced growth inhibition...