A5081730157- Multiple Myeloma Research and Treatments
- Lymphoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Pluripotent Stem Cells Research
- Atherosclerosis and Cardiovascular Diseases
- Angiogenesis and VEGF in Cancer
- Renal and related cancers
- Viral-associated cancers and disorders
- Computational Drug Discovery Methods
- Peptidase Inhibition and Analysis
- Cancer Genomics and Diagnostics
- Chronic Lymphocytic Leukemia Research
- Bioinformatics and Genomic Networks
- Ubiquitin and proteasome pathways
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Advanced Proteomics Techniques and Applications
- Gene expression and cancer classification
- Congenital heart defects research
- Pancreatic function and diabetes
- Tissue Engineering and Regenerative Medicine
- Molecular Biology Techniques and Applications
- Cancer Mechanisms and Therapy
- Chemokine receptors and signaling
- CNS Lymphoma Diagnosis and Treatment
Bristol-Myers Squibb (United States)
2020-2024
Center for Innovation
2021
Centro Andaluz de Biología Molecular y Medicina Regenerativa
2020
Bristol-Myers Squibb (Switzerland)
2012-2019
Instituto de Investigaciones Químicas
2019
Scarborough General Hospital
2019
Wellcome/MRC Cambridge Stem Cell Institute
2011-2016
Medical Research Council
2016
University of Cambridge
2008-2015
Chesterfield Royal Hospital
2013
The pluripotent status of embryonic stem cells (ESCs) confers upon them the capacity to differentiate into three primary germ layers, ectoderm, mesoderm and endoderm, from which all adult body are derived. An understanding mechanisms controlling pluripotency is thus essential for driving differentiation human cell types useful clinical applications. Activin/Nodal signalling pathway necessary maintain in ESCs mouse epiblast (EpiSCs), but molecular by it achieves this effect remain obscure....
Patients with newly diagnosed multiple myeloma (NDMM) high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used identify patients, each which has significant weaknesses. Inclusion molecular into risk stratification could resolve current challenges. In a genome-wide analysis largest set and clinical data established date from NDMM, as part Myeloma Genome Project, we defined DNA drivers...
BMP is thought to induce hESC differentiation toward multiple lineages including mesoderm and trophoblast. The BMP-induced trophoblast phenotype a long-standing paradox in stem cell biology. Here we readdressed function hESCs mouse epiblast-derived cells. We found that BMP4 cooperates with FGF2 (via ERK) inhibit endoderm differentiation. These conditions induced cells high levels of BRACHYURY (BRA) coexpressed CDX2. BRA was necessary for preceded CDX2 expression; both genes were essential...
Understanding the molecular mechanisms controlling early cell fate decisions in mammals is a major objective toward development of robust methods for differentiation human pluripotent stem cells into clinically relevant types. Here, we used embryonic and mouse epiblast to study specification definitive endoderm vitro. Using combination whole-genome expression chromatin immunoprecipitation (ChIP) deep sequencing (ChIP-seq) analyses, established an hierarchy transcription factors regulating...
Human embryonic stem cells (hESC) and induced pluripotent (iPSC) provide new prospects for studying human neurodevelopment modeling neurological disease. In particular, iPSC-derived neural permit a direct comparison of disease-relevant molecular pathways in neurons glia derived from patients healthy individuals. A prerequisite such comparative studies are robust protocols that efficiently yield standardized populations cell types. Here we show long-term self-renewing neuroepithelial-like...
Human embryonic stem cells have unique value for regenerative medicine, as they are capable of differentiating into a broad variety cell types. Therefore, defining the signalling pathways that control early fate decisions pluripotent represents major task. Moreover, modelling steps development in vitro may provide best approach to produce types with native properties. Here, we analysed function key developmental growth factors such Activin, FGF and BMP human cells. This analysis resulted...
The declining efficiency of myelin regeneration in individuals with multiple sclerosis has stimulated a search for ways by which it might be therapeutically enhanced. Here we have used gene expression profiling on purified murine oligodendrocyte progenitor cells (OPCs), the remyelinating adult CNS, to obtain comprehensive picture how they become activated after demyelination and this enables them contribute remyelination. We find that OPCs transcriptome more similar oligodendrocytes than...
Abstract The production of megakaryocytes (MKs)—the precursors blood platelets—from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach the large-scale generation MKs in chemically defined conditions using a forward programming strategy relying on concurrent exogenous expression three transcription factors: GATA1, FLI1 and TAL1. programmed proliferate differentiate culture several months with MK purity...
Abstract Dense surface models can be used to analyze 3D facial morphology by establishing a correspondence of thousands points across each face image. The provide dramatic visualizations face‐shape variation with potential for training physicians recognize the key components particular syndromes. We demonstrate their use visualize and shape differences in collection images that includes 280 controls (2 weeks 56 years age), 90 individuals Noonan syndrome (NS) (7 months years), 60...
Abstract Activin/Nodal signaling is necessary to maintain pluripotency of human embryonic stem cells (hESCs) and induce their differentiation toward endoderm. However, the mechanisms by which achieves these opposite functions remain unclear. To unravel mechanisms, we examined transcriptional network controlled in hESCs Smad2 Smad3, represent direct effectors signaling. These analyses reveal that Smad2/3 participate control core characterizing pluripotency, includes Oct-4, Nanog, FoxD3,...
The transcription factor brachyury (T, BRA) is one of the first markers gastrulation and lineage specification in vertebrates. Despite its wide use importance stem cell developmental biology, functional genomic targets human cells are largely unknown. Here, we differentiating embryonic to study role BRA activin A-induced endoderm BMP4-induced mesoderm progenitors. We show that has distinct genome-wide binding landscapes these two populations, interacts collaborates with SMAD1 or SMAD2/3...
Epigenetic reprogramming in early germ cells is critical toward the establishment of totipotency, but investigations germline events are intractable. An objective cell culture-based system could provide mechanistic insight on how key determinants primordial (PGCs), including Prdm14, induce to an epigenetic ground state. Here we show a Prdm14-Klf2 synergistic effect that can accelerate and enhance reversion mouse epiblast stem (epiSCs) naive pluripotent state, X reactivation DNA...
We have examined the transcriptional changes associated with differentiation from villous to extravillous trophoblast using a whole genome microarray. Villous (VT) is in contact maternal blood and mediates nutrient exchange whereas (EVT) invades decidua remodels uterine arteries. Using highly purified first trimester we identified over 3000 transcripts that are differentially expressed. Many of these represent novel functions pathways show co-ordinated up-regulation VT or EVT. In addition...
The design of effective cell replacement therapies requires detailed knowledge how embryonic stem cells form primary tissues, such as mesoderm or neurectoderm that later become skeletal muscle nervous system. Members the T-box transcription factor family are key in formation these but their underlying molecular activities poorly understood. Here, we define vivo genome-wide regulatory inputs proteins Brachyury, Eomesodermin, and VegT, which together maintain neuromesodermal determine...
Human epidermal stem cells express high levels of β1 integrins, delta-like 1 (DLL1) and the EGFR antagonist LRIG1. However, there is cell-to-cell variation in relative abundance DLL1 LRIG1 mRNA transcripts. Single-cell global gene expression profiling showed that undifferentiated fell into two clusters delineated by its binding partner syntenin. The DLL1(+) cluster had elevated genes associated with endocytosis, integrin-mediated adhesion receptor tyrosine kinase signalling. Differentially...
Background The tumor microenvironment (TME) is increasingly appreciated as an important determinant of cancer outcome, including in multiple myeloma (MM). However, most studies have been based on bone marrow (BM) aspirates, which often do not fully reflect the cellular content BM tissue itself. To address this limitation research, we systematically characterized whole (WBM) during premalignant, baseline, treatment, and post-treatment phases. Methods findings Between 2004 2019, 998 samples...