A5010108878- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Platelet Disorders and Treatments
- Blood disorders and treatments
- Blood groups and transfusion
- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- Chronic Lymphocytic Leukemia Research
- Endoplasmic Reticulum Stress and Disease
- Renal Diseases and Glomerulopathies
- Eosinophilic Disorders and Syndromes
- Neutropenia and Cancer Infections
- Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Hematological disorders and diagnostics
- Kruppel-like factors research
- RNA modifications and cancer
- Neonatal Respiratory Health Research
- Liver Disease Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Ubiquitin and proteasome pathways
- Intestinal Malrotation and Obstruction Disorders
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
Harvard University
2019-2024
Brigham and Women's Hospital
2018-2024
Radboud University Nijmegen
2013-2024
Radboud University Medical Center
2013-2024
Radboud Institute for Molecular Life Sciences
2013-2021
University Medical Center
2013-2019
The gray platelet syndrome is a hereditary, usually autosomal recessive bleeding disorder caused by deficiency of alpha granules in platelets. We detected nonsense mutation the gene encoding transcription factor GFI1B (growth independent 1B) that causes dominant syndrome. Both platelets and megakaryocytes had abnormal marker expression. In addition, dysplastic features, they were abnormally distributed bone marrow. mutant protein inhibited nonmutant transcriptional activity dominant-negative...
In 11q23 leukemias, the N-terminal part of mixed lineage leukemia (MLL) gene is fused to >60 different partner genes. order define a core set MLL rearranged targets, we investigated genome-wide binding MLL-AF9 and MLL-AF4 fusion proteins associated epigenetic signatures in acute myeloid (AML) cell lines THP-1 MV4-11. We uncovered both common as well specific target genes, which were all marked by H3K79me2, H3K27ac H3K4me3. Apart from promoter binding, also identified at subsets...
Inherited platelet disorders are a heterogeneous group of rare diseases, caused by inherited defects in production and/or function. Their genetic diagnosis would benefit clinical care, prognosis and preventative treatments. Until recently, this has usually been performed via Sanger sequencing limited number candidate genes. High-throughput is revolutionizing the including bleeding disorders. We have designed novel high-throughput platform to investigate unknown molecular pathology cohort 82...
The majority of JAK2 V617F -negative myeloproliferative neoplasms (MPNs) have disease-initiating frameshift mutations in calreticulin ( CALR ), resulting a common carboxyl-terminal mutant fragment (CALR MUT representing an attractive source neoantigens for cancer vaccines. However, studies shown that -specific T cells are rare patients with MPN unknown reasons. We examined class I major histocompatibility complex (MHC-I) allele frequencies from two independent cohorts. observed MHC-I alleles...
To identify novel therapeutic targets in acute myeloid leukemia (AML), we examined kinase expression patterns primary AML samples. We found that the serine/threonine IKBKE, a noncanonical IkB kinase, is expressed at higher levels cells compared with normal hematopoietic cells. Inhibiting or its close homolog TANK-binding 1 (TBK1), by either short hairpin RNA knockdown pharmacological compounds, induces apoptosis and reduces viability of Using gene profiling set enrichment analysis,...
Calreticulin (CALR) mutations are frequent, disease-initiating events in myeloproliferative neoplasms (MPNs). Although the biological mechanism by which CALR cause MPNs has been elucidated, there currently no clonally selective therapies for CALR-mutant MPNs. To identify unique genetic dependencies MPNs, we performed a whole-genome clustered regularly interspaced short palindromic repeats (CRISPR) knockout depletion screen mutant CALR-transformed hematopoietic cells. We found that genes...
Novel therapeutics are urgently needed to prevent opportunistic infections in immunocompromised individuals undergoing cancer treatments or other immune-suppressive therapies. Trained immunity is a promising strategy reduce this burden of disease. We previously demonstrated that mesenchymal stromal cells (MSCs) preconditioned with class A CpG oligodeoxynucleotide (CpG-ODN), Toll-like receptor 9 (TLR9) agonist, can augment emergency granulopoiesis murine model neutropenic sepsis. Here, we...
Dominant-negative mutations in the transcription factor Growth Factor Independence-1B (GFI1B), such as GFI1BQ287*, cause a bleeding disorder characterized by plethora of megakaryocyte and platelet abnormalities. The deregulated molecular mechanisms pathways are unknown. Here we show that both normal Q287* mutant GFI1B interacted most strongly with lysine specific demethylase-1 – REST corepressor - histone deacetylase (LSD1-RCOR-HDAC) complex megakaryoblasts. Sequestration this GFI1BQ287*...
Abstract Patients with immune deficiencies from cancers and associated treatments represent a growing population within the intensive care unit increased risk of morbidity mortality sepsis. Mesenchymal stromal cells (MSCs) are an integral part hematopoietic niche express toll-like receptors, making them candidate to sense translate pathogenic signals into innate response. In this study, we demonstrate that MSCs administered therapeutically in murine model radiation-associated neutropenia...
Although the involvement of glycan structures in diseases has long been recognized, their detailed and high-throughput investigation only recently made possible due to technological advancements. For this reason, glycosylation is a generally understudied phenomenon, however it could provide critical information on pathobiology many disorders by virtue its widespread abundance role protein function. Here, we focus myeloid malignancies, conditions for which survival rates are often poor...