A5056490394- Epigenetics and DNA Methylation
- Hemoglobinopathies and Related Disorders
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Erythrocyte Function and Pathophysiology
- Acute Myeloid Leukemia Research
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Gene expression and cancer classification
- Molecular Biology Techniques and Applications
- Connective Tissue Growth Factor Research
- Prenatal Screening and Diagnostics
- Protein Degradation and Inhibitors
- Zebrafish Biomedical Research Applications
- Systemic Sclerosis and Related Diseases
- Cell Adhesion Molecules Research
- Genetic Syndromes and Imprinting
- Dermatologic Treatments and Research
- HIV/AIDS drug development and treatment
- Bone and Dental Protein Studies
- interferon and immune responses
- Helicobacter pylori-related gastroenterology studies
- Parvovirus B19 Infection Studies
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
Acetylon Pharmaceuticals (United States)
2012-2017
University of Massachusetts Chan Medical School
2009-2012
Biogen (United States)
2002-2008
University of Washington
1999
Abstract Objective To determine whether biopsy specimens obtained from systemic sclerosis (SSc) lesions show a distinctive gene profile, that profile is maintained in fibroblasts cultured SSc skin specimens, and results tissue multiple clinical centers can be combined to yield useful observations this rare disease. Methods Biopsy samples passaged were stored RNAlater solution prior processing for RNA. RNA control as well explanted passage 4 fibroblasts, 9 patients controls was hybridized...
During red blood cell development, differentiation and cycle progression are intimately uniquely linked through interdependent mechanisms involving the erythroid transcriptional suppressor PU.1 cyclin-dependent kinase inhibitor p57KIP2.
In the mammalian genome, 5'-CpG-3' dinucleotides are frequently methylated, correlating with transcriptional silencing. Genome-wide demethylation is thought to occur only twice during development, in primordial germ cells and pre-implantation embryo. These events followed by de novo methylation, setting up a pattern inherited throughout development modified at tissue-specific loci. We studied DNA methylation differentiating mouse erythroblasts vivo using genomic-scale reduced representation...
The study of erythropoiesis aims to understand how red cells are formed from earlier hematopoietic and erythroid progenitors. Specifically, the rate cell formation is regulated by hormone erythropoietin (Epo), whose synthesis triggered tissue hypoxia. A threat adequate oxygenation results in a rapid increase Epo, driving an erythropoietic rate, process known as stress response. resulting number circulating improves oxygen delivery. An efficient response therefore critical survival recovery...
Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (ALL) expressing BCR-ABL1 oncoprotein is a major subclass of ALL with poor prognosis. BCR-ABL1-expressing leukemic cells are highly dependent on double-strand break (DSB) repair signals for their survival. Here we report that first-in-class HDAC1,2 selective inhibitor and doxorubicin (a hyper-CVAD chemotherapy regimen component) impair DSB networks in Ph+ using common as well distinct mechanisms. The but not...
Abstract Objective Previously published studies have demonstrated that a majority of systemic sclerosis (SSc) fibroblasts exhibit elevated levels transforming growth factor β type I receptor (TGFβRI). An experimental model recapitulates this condition was established in control dermal by titrating the dose adenovirus vector expressing TGFβRI (AdTGFβRI). The present study undertaken to determine functional consequences increased SSc. Methods Gene array analysis transduced with AdTGFβRI...
Gain-of-function mutations in the catalytic site of EZH2 (Enhancer Zeste Homologue 2), is observed about 22% diffuse large B-cell lymphoma (DLBCL) cases. Here we show that selective inhibition histone deacetylase 1,2 (HDAC1,2) activity using a small molecule inhibitor causes cytotoxic or cytostatic effects gain-of-function mutant (EZH2GOF) DLBCL cells. Our results blocking HDAC1,2 increases global H3K27ac without causing concomitant decrease H3K27me3 levels. data shows sufficient to present...
Therapeutic intervention aimed at reactivation of fetal hemoglobin protein (HbF) is a promising approach for ameliorating sickle cell disease (SCD) and β-thalassemia. Previous studies showed genetic knockdown histone deacetylase (HDAC) 1 or 2 sufficient to induce HbF. Here we show that ACY-957, selective chemical inhibitor HDAC1 (HDAC1/2), elicits dose time dependent induction γ-globin mRNA (HBG) HbF in cultured primary cells derived from healthy individuals patients. Gene expression...
The study of erythropoiesis aims to understand how red cells are formed from earlier hematopoietic and erythroid progenitors. Specifically, the rate cell formation is regulated by hormone erythropoietin (Epo), whose synthesis triggered tissue hypoxia. A threat adequate oxygenation results in a rapid increase Epo, driving an erythropoietic rate, process known as stress response. resulting number circulating improves oxygen delivery. An efficient response therefore critical survival recovery...
Human genetics has validated de-repression of fetal gamma globin (HBG) in adult erythroblasts as a powerful therapeutic paradigm diseases involving defective beta (HBB)1. To identify factors involved the switch from HBG to HBB expression, we performed Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq)2 on sorted erythroid lineage cells derived bone marrow (BM) or cord blood (CB), representing and states, respectively. BM CB cell ATAC-seq profile comparisons...
The integrin α6β4 is defined as an adhesion receptor for laminins. Referred to 'β4', this plays a key role in the progression of various carcinomas through its ability orchestrate signal transduction events and promote cell motility. To identify novel downstream effectors β4 function breast cancer, microRNAs (miRNAs) were examined because their extensive links tumorigenesis regulate gene expression globally. Two carcinoma lines collection invasive with varying used assess effect on miRNA...
Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic stem cell disorders characterized by defects in differentiation and increased proliferation neoplastic precursor cells. Outcomes for patients with AML remain poor, highlighting the need novel treatment options. Aberrant epigenetic regulation plays an important role pathogenesis AML, inhibitors DNA methyltransferase or histone deacetylase (HDAC) enzymes have exhibited activity preclinical models. Combination studies HDAC...
The use of microarrays to monitor gene expression has become a standard research tool at both academic and industrial institutions. Quality control common printing defects during DNA deposition onto glass substrates is critical maintaining data integrity preventing the needless consumption precious RNA, labeling reagents, time. Here we demonstrate nondestructive method for monitoring quality every spot on chip microarray production run. We have identified many manufacturing defects, while...