A5021024165- RNA modifications and cancer
- Biochemical and Molecular Research
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Genetic and Kidney Cyst Diseases
- PI3K/AKT/mTOR signaling in cancer
- Acute Lymphoblastic Leukemia research
- DNA Repair Mechanisms
- Protein Tyrosine Phosphatases
- CRISPR and Genetic Engineering
- Adenosine and Purinergic Signaling
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Protein Kinase Regulation and GTPase Signaling
- Genomics and Rare Diseases
- Childhood Cancer Survivors' Quality of Life
- Nuclear Structure and Function
- Virus-based gene therapy research
- Genetics and Neurodevelopmental Disorders
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Cancer Cells and Metastasis
University of Copenhagen
2022-2025
Novo Nordisk Foundation
2022-2024
KU Leuven
2017-2023
Serine/Threonine phosphoprotein phosphatases (PPPs, PP1-PP7) are conserved metalloenzymes and central to intracellular signaling in eukaryotes, but the details of their regulation is poorly understood. To address this, we performed genome-wide CRISPR knockout focused base editor screens PPP perturbed conditions establish a high-resolution functional map that pinpoints novel regulatory mechanisms. Through identify orphan reductase CYB5R4 as an evolutionarily activator PP4 PP6, not closely...
Protein phosphatase 2A (PP2A) complexes counteract many oncogenic kinase pathways. In cancer cells, PP2A function can be compromised by several mechanisms, including sporadic mutations in its scaffolding A and regulatory B subunits or more frequently through overexpression of cellular inhibitors. Here, we identify a novel genetic mechanism which is recurrently affected human cancer, involving haploinsufficiency PPP2R4, gene encoding the activator PTPA. Notably, up to 70% patients showed...
Pancreatic ductal adenocarcinoma (PDAC) has a low survival, its incidence is rising and little therapeutic improvements are expected in the near future. It been observed that Epithelial-to-Mesenchymal transition (EMT) contributes (including PDAC) to more aggressive cancer phenotype. Additionally, largely unexplored, studies indicate mechanistic interplay between Protein Phosphatase Type 2A (PP2A) enzymes EMT could offer treatment opportunities. The aim was investigate relation of PP2A...
Short linear motifs (SLiMs) are the most ubiquitous protein interaction modules in unstructured regions of human proteome. Despite their central role function, our understanding contribution SLiMs to cellular homeostasis remains limited. To address this, we designed base editor libraries precisely mutate all curated and a set computationally predicted instances defined by SLiM-like evolutionary patterns. By targeting 7,293 SLiM containing with 80,473 mutations, define dependency map...
Chronic lung diseases (CLDs) represent a set of disorders characterized by the progressive loss proper function. Among severe CLDs, incidence chronic obstructive pulmonary disease (COPD) and idiopathic fibrosis (IPF) has grown over last decades, mainly in elderly population. Several studies have highlighted an increased expression senescence-related markers resident progenitor cells COPD IPF, possibly undermining epithelial integrity contributing to progression aggravation both diseases....
Abstract Translesion DNA synthesis (TLS) is an essential process that allows cells to bypass lesions encountered during replication and emerging as a primary target of chemotherapy. Among vertebrate polymerases, polymerase kappa (Pol() has the unique ability minor groove adducts in vitro. However, Pol(is also required for overcome major but basis this requirement unclear. Here, we combine CRISPR base editor screening technology human with TLS analysis defined Xenopus egg extracts unravel...
<p>Antibodies used in this study.</p>
<div>Abstract<p>Protein phosphatase 2A (PP2A) complexes counteract many oncogenic kinase pathways. In cancer cells, PP2A function can be compromised by several mechanisms, including sporadic mutations in its scaffolding A and regulatory B subunits or more frequently through overexpression of cellular inhibitors. Here, we identify a novel genetic mechanism which is recurrently affected human cancer, involving haploinsufficiency <i>PPP2R4</i>, gene encoding the...
<p>Histopathology pictures of neoplastic abnormalities in Ppp2r4 gene-trapped mice.</p>
<p>PTPA and PP2A subunit expression in WT, Ptpa +/gt gt/gt healthy neoplastic spleens.</p>
<p>Phosphatase assays in immunoprecipitates of several endogenous PP2A B-type subunits: time courses.</p>
<p>Oligonucleotides used for site-directed mutagenesis of PTPA, and genomic characterization Ppp2r4 gene-trapped ES-cells mice.</p>
<p>Oligonucleotides used for site-directed mutagenesis of PTPA, and genomic characterization Ppp2r4 gene-trapped ES-cells mice.</p>
<p>Overview of cancer-associated PPP2R4 exome mutations found in COSMIC and cBioportal cancer databases.</p>
<p>Antibodies used in this study.</p>
<p>Supplementary Figure legends</p>
<p>Supplementary Figure legends</p>
<div>Abstract<p>Protein phosphatase 2A (PP2A) complexes counteract many oncogenic kinase pathways. In cancer cells, PP2A function can be compromised by several mechanisms, including sporadic mutations in its scaffolding A and regulatory B subunits or more frequently through overexpression of cellular inhibitors. Here, we identify a novel genetic mechanism which is recurrently affected human cancer, involving haploinsufficiency <i>PPP2R4</i>, gene encoding the...
<p>Phosphatase assays in immunoprecipitates of several endogenous PP2A B-type subunits: time courses.</p>