A5049553270- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Molecular Biology Techniques and Applications
- Sirtuins and Resveratrol in Medicine
- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Histone Deacetylase Inhibitors Research
- Genomics and Phylogenetic Studies
- Genetics, Bioinformatics, and Biomedical Research
- HIV Research and Treatment
- Polyamine Metabolism and Applications
- Genetic factors in colorectal cancer
- Plant responses to water stress
- Adenosine and Purinergic Signaling
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Genomics and Rare Diseases
- Cannabis and Cannabinoid Research
- Hippo pathway signaling and YAP/TAZ
- Pancreatic and Hepatic Oncology Research
Karolinska Institutet
2010-2022
Constellation Pharmaceuticals (United States)
2021
University of Cambridge
2016-2020
Wellcome Trust
2017-2018
Addenbrooke's Hospital
2016
Abstract Contact inhibition enables noncancerous cells to cease proliferation and growth when they contact each other. This characteristic is lost undergo malignant transformation, leading uncontrolled solid tumor formation. Here we report that autophagy compromised in contact-inhibited 2D or 3D-soft extracellular matrix cultures. In such cells, YAP/TAZ fail co-transcriptionally regulate the expression of myosin-II genes, resulting loss F-actin stress fibers, which impairs autophagosome The...
DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding biology. Most sequencing approaches address either genetics or epigenetics thus capture incomplete information. Methods widely used detect bases fail common C-to-T mutations distinguish 5-methylcytosine from 5-hydroxymethylcytosine. We present a single base-resolution methodology that sequences complete the two most cytosine modifications workflow. is copied enzymatically...
Macroautophagy/autophagy is a conserved catabolic pathway that targets cytoplasmic components for their degradation and recycling in an autophagosome-dependent lysosomal manner. Under physiological conditions, this process maintains cellular homeostasis. However, autophagy can be stimulated upon different forms of stress, ranging from nutrient starvation to exposure drugs. Thus, seen as central component the integrated adaptive stress response. Here, we report even brief induction coupled
Abstract Early detection of cancer will improve survival rates. The blood biomarker 5-hydroxymethylcytosine has been shown to discriminate cancer. In a large covariate-controlled study over two thousand individual samples, we created, tested and explored the properties 5-hydroxymethylcytosine-based classifier detect colorectal (CRC). an independent validation sample set, discriminated CRC samples from controls with area under receiver operating characteristic curve (AUC) 90% (95% CI [87,...
Abstract Macroautophagy/autophagy is an evolutionarily conserved and tightly regulated catabolic process involved in the maintenance of cellular homeostasis whose dysregulation implicated several pathological processes. Autophagy begins with formation phagophores that engulf cytoplasmic cargo mature into double-membrane autophagosomes; latter fuse lysosomes/vacuoles for degradation recycling. Here, we report yeast Set2, a histone lysine methyltransferase, its mammalian homolog, SETD2, both...
Abstract The combinatorial power of genetics and epigenetics is vital to understanding biology in healthy cancerous states. Utilizing a recent novel approach, we enable the simultaneous identification modified cytosine canonical bases A, C, T & G an enzymatic single-workflow solution. Generating this information across whole genome provides much-improved genetic epigenetic changes, but can require large amount sequencing, particularly when exploring at depth. Enrichment protocols such as...
Abstract Liquid biopsy for profiling of cell free DNA (cfDNA) in blood holds huge promise to transform how we experience and manage cancer by early detection identification residual disease subtype. While work liquid focused on the actionable somatic variations at specific loci, past decade has seen an expansion into non-genetic features, notably methylation. 5-methylcytosine (5-mC) profiles are differential from non-cancer many more loci so provide a stronger signal. Moreover, recent...
Abstract DNA comprises molecular information stored via genetic bases (G, C, T, A) and also epigenetic bases, principally 5-methylcytosine (5mC) 5-hydroxymethylcytosine (5hmC). Both are vital to our understanding of biology disease states. Most sequencing approaches address either genetics or epigenetics thus capture incomplete information. Methods widely used detect typically fail common C-to-T mutations distinguish 5mC from 5hmC. Here, we present a single-base-resolution methodology that...
Abstract Early detection of colorectal cancer (CRC) will improve survival rates. We created a classifier to detect CRC, based on 5-hydroxymethylcytosine levels in cell free DNA isolated from blood samples 2198 individuals. Our discriminated CRC controls with an area under the receiver operating characteristic curve (AUC) 90% (sensitivity was 55% at 95% specificity). Performance similar for early stage 1 (AUC 89%) and late 4 94%). independent proportion tumor-DNA DNA. expanded include...
Abstract Liquid biopsy for profiling of cell free DNA (cfDNA) in blood holds huge promise to transform how we experience and manage cancer by early detection identification residual disease subtype. However, a standard draw yields an average only 10 ng cfDNA, which derived from the tumor is small minority. Therefore, are faced with dilemma when utilizing limited sample obtain maximum information. Genetic sequencing provides information on actionable somatic mutations but few loci minority...