A5031611528- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Fibroblast Growth Factor Research
- Kruppel-like factors research
- RNA modifications and cancer
- Hedgehog Signaling Pathway Studies
- Colorectal Cancer Treatments and Studies
- Cancer, Hypoxia, and Metabolism
- TGF-β signaling in diseases
- Peptidase Inhibition and Analysis
- Uterine Myomas and Treatments
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- DNA and Nucleic Acid Chemistry
- Genomics and Phylogenetic Studies
- Lymphatic System and Diseases
- Protein Degradation and Inhibitors
- Genetic Associations and Epidemiology
- Connective tissue disorders research
- Chromosomal and Genetic Variations
University of Cambridge
2017-2025
Wellcome Sanger Institute
2025
University of Helsinki
2016-2025
Karolinska Institutet
2016-2025
Genomics (United Kingdom)
2020-2025
Institute for Molecular Medicine Finland
2006-2023
Science for Life Laboratory
2011-2023
Public Health Institute
2023
Karolinska University Hospital
2013-2021
University of Oslo
2021
The steroidal alkaloid cyclopamine has both teratogenic and antitumor activities arising from its ability to specifically block cellular responses vertebrate Hedgehog signaling. We show here, using photoaffinity fluorescent derivatives, that this inhibitory effect is mediated by direct binding of the heptahelical bundle Smoothened (Smo). Cyclopamine also can reverse retention partially misfolded Smo in endoplasmic reticulum, presumably through binding-mediated effects on protein...
Positives and negatives of methylated CpG When the DNA bases cytosine guanine are next to each other, a methyl group is generally added pyrimidine, generating mCpG dinucleotide. This modification alters structure but can also affect function by inhibiting transcription factor (TF) binding. Yin et al. systematically analyzed effect methylation on binding 542 human TFs (see Perspective Hughes Lambert). In addition some TFs, they found that mCpGs promote others, particularly involved in...
Smoothened (Smo), a distant relative of G protein-coupled receptors, mediates Hedgehog (Hh) signaling during embryonic development and can initiate or transmit ligand-independent pathway activation in tumorigenesis. Although the cellular mechanisms that regulate Smo function remain unclear, direct inhibition by cyclopamine, plant-derived steroidal alkaloid, suggests endogenous small molecules may be involved. Here we demonstrate SAG, chlorobenzothiophene-containing Hh agonist, binds to...
Vascular endothelial growth factor (VEGF) is a key regulator of blood vessel development in embryos and angiogenesis adult tissues. Unlike VEGF, the related VEGF-C stimulates lymphatic vessels through its specific receptor VEGFR-3. Here it shown that targeted inactivation gene encoding VEGFR-3 resulted defective early mouse embryos. Vasculogenesis occurred, but large became abnormally organized with lumens, leading to fluid accumulation pericardial cavity cardiovascular failure at embryonic...
Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth established tumors unclear. Here, we investigate therapeutic efficacy Hh antagonist cyclopamine preclinical models medulloblastoma, most common malignant brain tumor children. Cyclopamine treatment murine medulloblastoma cells blocked proliferation vitro and induced changes gene expression consistent neuronal differentiation loss stem cell–like character. This compound...
Uterine leiomyomas, or fibroids, are benign tumors that affect millions of women worldwide and can cause considerable morbidity. To study the genetic basis this tumor type, we examined 18 uterine leiomyomas derived from 17 different patients by exome sequencing identified tumor-specific mutations in mediator complex subunit 12 (MED12) gene 10. Through analysis 207 additional tumors, determined MED12 is altered 70% (159 225) a total 80 patients. The Mediator 26-subunit transcriptional...
The role of latent transforming growth factor-beta (TGF-beta) binding protein (LTBP) in the association TGF-beta 1 to extracellular matrix cultured fibroblasts and HT-1080 fibrosarcoma cells was studied by immunochemical methods. matrices were isolated from cells, levels LTBP estimated immunoblotting immunoprecipitation. LTBP, 1, its propeptide (latency-associated peptide, LAP) found associate matrix. Immunoblotting analysis indicated that treatment with plasmin resulted a concomitant time...
The genetic code—the binding specificity of all transfer-RNAs—defines how protein primary structure is determined by DNA sequence. also dictates when and where proteins are expressed, this information encoded in a pattern specific sequence motifs that recognized transcription factors. However, the DNA-binding only known for small fraction ∼1400 human factors (TFs). We describe here high-throughput method analyzing factor based on systematic evolution ligands exponential enrichment (SELEX)...