A5070098454- Acute Lymphoblastic Leukemia research
- Cytokine Signaling Pathways and Interactions
- Chronic Myeloid Leukemia Treatments
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- T-cell and Retrovirus Studies
- Chronic Lymphocytic Leukemia Research
- Advanced biosensing and bioanalysis techniques
- RNA Research and Splicing
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hedgehog Signaling Pathway Studies
- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- Lung Cancer Research Studies
- Reproductive System and Pregnancy
- Advanced Fluorescence Microscopy Techniques
- NF-κB Signaling Pathways
- Lymphoma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Animal Genetics and Reproduction
- Biosensors and Analytical Detection
- MicroRNA in disease regulation
- Genetic and Kidney Cyst Diseases
VIB-KU Leuven Center for Brain & Disease Research
2022-2025
KU Leuven
2012-2025
VIB-KU Leuven Center for Cancer Biology
2012-2025
Wellcome Sanger Institute
2019
Cancer Genetics (United States)
2019
Center for Human Genetics
2013-2019
Munich Leukemia Laboratory (Germany)
2019
Transcriptional enhancers act as docking stations for combinations of transcription factors and thereby regulate spatiotemporal activation their target genes
Abstract In the mammalian liver, hepatocytes exhibit diverse metabolic and functional profiles based on their location within liver lobule. However, it is unclear whether this spatial variation, called zonation, governed by a well-defined gene regulatory code. Here, using combination of single-cell multiomics, omics, massively parallel reporter assays deep learning, we mapped enhancer-gene networks across mouse cell types. We found that zonation affects expression chromatin accessibility in...
Combinations of transcription factors govern the identity cell types, which is reflected by genomic enhancer codes. We used deep learning to characterize these codes and devised three metrics compare types in telencephalon across amniotes. To this end, we generated single-cell multiome spatially resolved transcriptomics data chicken telencephalon. Enhancer orthologous nonneuronal γ-aminobutyric acid–mediated (GABAergic) show a high degree similarity amniotes, whereas excitatory neurons...
Abstract Leukemia is caused by the accumulation of multiple genomic lesions in hematopoietic precursor cells. However, how these events cooperate during oncogenic transformation remains poorly understood. We studied cooperation between activated JAK3/STAT5 signaling and HOXA9 overexpression, two identified as significantly co-occurring T-cell acute lymphoblastic leukemia. Expression mutant JAK3 led to a rapid development leukemia originating from multipotent or lymphoid-committed...
Spatial transcriptomics workflows using barcoded capture arrays are commonly used for resolving gene expression in tissues. However, existing techniques either limited by array density or cost prohibitive large-scale atlasing. We present Nova-ST, a dense nano-patterned spatial technique derived from randomly Illumina sequencing flow cells. Nova-ST enables customized, low-cost, flexible, and high-resolution profiling of large tissue sections. Benchmarking on mouse brain sections demonstrates...
Combinations of transcription factors govern the identity cell types, which is reflected by enhancer codes in cis-regulatory genomic regions. Cell type-specific at nucleotide-level resolution have not yet been characterized for mammalian neocortex. It currently unknown whether these are conserved other vertebrate brains, and they informative to resolve homology relationships species that lack a neocortex such as birds. To compare types from with those bird pallium, we generated single-cell...
With the advent of whole-genome and whole-exome sequencing, high-quality catalogs recurrently mutated cancer genes are becoming available for many types. Increasing access to sequencing technology, including bench-top sequencers, provide opportunity re-sequence a limited set across patient cohort with processing time. Here, we re-sequenced in T-cell acute lymphoblastic leukemia (T-ALL) using Nimblegen sequence capture coupled Roche/454 technology. First, investigated how maximal sensitivity...
Abstract Spatial transcriptomics workflows using barcoded capture arrays are commonly used for resolving gene expression in tissues. However, existing techniques either limited by array density or cost prohibitive large scale atlasing. We present Nova-ST, a dense nano-patterned spatial technique derived from randomly Illumina sequencing flow cells. Nova-ST enables customized, low cost, flexible, and high-resolution profiling of tissue sections. Benchmarking on mouse brain sections...
The NUP214-ABL1 fusion protein is a constitutively active tyrosine kinase that found in 6% of patients with T-cell acute lymphoblastic leukemia and promotes proliferation survival T-lymphoblasts. Although sensitive to ABL1 inhibitors, development resistance these compounds major clinical problem, underlining the need for additional drug targets sparsely studied signaling network. In this work, we identify validate SRC family LCK as whose activity absolutely required cells depend on activity....
Cilia project from the surface of most vertebrate cells and are important for several physiological developmental processes. Ciliary defects linked to a variety human diseases, named ciliopathies, underscoring importance understanding signaling pathways involved in cilia formation maintenance. In this paper, we identified Rer1p as first endoplasmic reticulum/cis-Golgi–localized membrane protein ciliogenesis. Rer1p, quality control receptor, was highly expressed zebrafish ciliated organs...
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of the lymphocytes that driven by cooperation various mutations. Constitutive activation JAK-STAT signaling observed in one-third T-ALL patients and caused activating mutations interleukin 7 receptor alpha chain (IL7R), Janus kinases JAK1 or JAK3, Signal transducer activator transcription 5B (STAT5B).1–3 STAT5B are most frequently N642H variant associated with unfavorable prognosis higher risk relapse.1,2,4,5 We set out...
Abstract Mucosa‐associated lymphoid tissue 1 (Malt1) regulates immune cell function by mediating the activation of nuclear factor κB (NF‐κB) signaling through both its adaptor and proteolytic function. Malt1 is also a target own protease activity this self‐cleavage further contributes to NF‐κB activity. Until now, functional distinction between general in regulating remained unclear. Here we demonstrate, using new mouse model, importance expression genes subsequent T activation....
Cell type identity is encoded by gene regulatory networks (GRN), in which transcription factors (TFs) bind to enhancers regulate target expression. In the mammalian liver, lineage TFs have been characterized for main cell types, including hepatocytes. Hepatocytes cover a relatively broad cellular state space, as they differ significantly their metabolic state, and function, depending on position with respect central or portal vein liver lobule. It unclear whether this spatially defined...
<p>Supplemental tables and figures</p>
<p>Supplemental tables and figures</p>
<div>Abstract<p>Leukemia is caused by the accumulation of multiple genomic lesions in hematopoietic precursor cells. However, how these events cooperate during oncogenic transformation remains poorly understood. We studied cooperation between activated JAK3/STAT5 signaling and HOXA9 overexpression, two identified as significantly co-occurring T-cell acute lymphoblastic leukemia. Expression mutant JAK3 led to a rapid development leukemia originating from multipotent or...
<div>Abstract<p>Leukemia is caused by the accumulation of multiple genomic lesions in hematopoietic precursor cells. However, how these events cooperate during oncogenic transformation remains poorly understood. We studied cooperation between activated JAK3/STAT5 signaling and HOXA9 overexpression, two identified as significantly co-occurring T-cell acute lymphoblastic leukemia. Expression mutant JAK3 led to a rapid development leukemia originating from multipotent or...