A5073233196- Wnt/β-catenin signaling in development and cancer
- Developmental Biology and Gene Regulation
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- RNA Research and Splicing
- Liver physiology and pathology
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- Pluripotent Stem Cells Research
- Congenital heart defects research
- Hedgehog Signaling Pathway Studies
- Pancreatic function and diabetes
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Bioinformatics and Genomic Networks
- Liver Disease Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Malaria Research and Control
- MicroRNA in disease regulation
- NF-κB Signaling Pathways
- Fungal and yeast genetics research
- 14-3-3 protein interactions
- RNA Interference and Gene Delivery
Novartis (Switzerland)
2015-2024
Novartis Institutes for BioMedical Research
2013-2023
Harvard University Press
2014
Novartis Foundation
2009
European Molecular Biology Laboratory
1999-2002
European Molecular Biology Laboratory
2001
European Bioinformatics Institute
1999
Howard Hughes Medical Institute
1997-1998
University of California, Los Angeles
1996-1998
European Molecular Biology Organization
1998
YAP1 is a major effector of the Hippo pathway and well-established oncogene. Elevated activity due to mutations in components or amplification observed several types human cancers. Here we investigated its genomic binding landscape YAP1-activated cancer cells, as well non-transformed cells. We demonstrate that TEAD transcription factors mediate chromatin-binding genome-wide, further explaining their dominant role primary mediators YAP1-transcriptional activity. Moreover, show largely exerts...
Humans lacking sclerostin display progressive bone overgrowth due to increased formation. Although it is well established that an osteocyte-secreted formation inhibitor, the underlying molecular mechanisms are not fully elucidated. We identified in tandem affinity purification proteomics screens LRP4 (low density lipoprotein-related protein 4) as a interaction partner. Biochemical assays with recombinant proteins confirmed direct. Interestingly, vitro overexpression and RNAi-mediated...
The Yes‐associated protein (YAP)/Hippo pathway has been implicated in tissue development, regeneration, and tumorigenesis. However, its role cholangiocarcinoma (CC) is not established. We show that YAP activation a common feature CC patient biopsies human cell lines. Using microarray expression profiling of cells with overexpressed or down‐regulated YAP, we regulates genes involved proliferation, apoptosis, angiogenesis. activity promotes growth vitro vivo by functionally interacting TEAD...
Sickle cell disease (SCD) is a prevalent, life-threatening condition attributable to heritable mutation in β-hemoglobin. Therapeutic induction of fetal hemoglobin (HbF) can ameliorate complications and has been intently pursued. However, safe effective small-molecule inducers HbF remain elusive. We report the discovery dWIZ-1 dWIZ-2, molecular glue degraders WIZ transcription factor that robustly induce erythroblasts. Phenotypic screening cereblon (CRBN)-biased chemical library revealed as...
ABSTRACT Paraxial Protocadherin (PAPC) encodes a transmembrane protein expressed initially in Spemann’s organizer and then paraxial mesoderm. Together with another member of the protocadherin family, Axial (AXPC), it subdivides gastrulating mesoderm into axial domains. PAPC has potent homotypic cell adhesion activity dissociation reaggregation assays. Gain- loss-of-function microinjection studies indicate that plays an important role convergence extension movements drive Xenopus...
ABSTRACT Bone morphogenetic proteins (Bmps) are signaling molecules that have been implicated in a variety of inductive processes. We report here zebrafish Bmp7 is disrupted snailhouse (snh) mutants. The allele snhst1 translocation deleting the bmp7 gene, while snhty68 displays Val→Gly exhange conserved motif prodomain. mutation temperature-sensitive, leading to severalfold reduced activity mutant at 28°C and non-detectable 33°C. This prodomain lesion affects secretion and/or stability...
ABSTRACT Signaling by members of the TGFβ superfamily is thought to be transduced Smad proteins. Here, we describe a zebrafish mutant in smad5, designated somitabun (sbn). The dominant maternal and zygotic effect sbntc24 mutation caused change single amino acid L3 loop Smad5 protein which transforms into an antimorphic version, inhibiting wild-type related sbn embryos are strongly dorsalized, similarly mutants Bmp2b, its putative upstream signal. Double analyses RNA injection experiments...
Host factor pathways are known to be essential for hepatitis C virus (HCV) infection and replication in human liver cells. To search novel host proteins required HCV replication, we screened a subgenomic genotype 1b replicon cell line (Luc-1b) with kinome druggable collection of 20,779 siRNAs. We identified validated several enzymes including class III phosphatidylinositol 4-kinases (PI4KA PI4KB), carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD), mevalonate...
The polarization of eukaryotic cells is controlled by the concerted activities asymmetrically localized proteins. PAR proteins, first identified in Caenorhabditis elegans, are common regulators cell polarity conserved from nematode and flies to man. However, little known about molecular mechanisms which these proteins protein complexes establish mammals. We have mapped multiprotein formed around putative human Par orthologs MARK4 (microtubule-associated protein/microtubule...