A5055700623- Pancreatic function and diabetes
- Pluripotent Stem Cells Research
- Cardiac Fibrosis and Remodeling
- Congenital heart defects research
- Tissue Engineering and Regenerative Medicine
- Diabetes and associated disorders
- Extracellular vesicles in disease
- Immune cells in cancer
- Congenital Heart Disease Studies
- Single-cell and spatial transcriptomics
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Cardiac Structural Anomalies and Repair
- 3D Printing in Biomedical Research
- Pulmonary Hypertension Research and Treatments
- Cancer Cells and Metastasis
- Cardiovascular Function and Risk Factors
- Cardiac Valve Diseases and Treatments
- Coronary Artery Anomalies
University of Oxford
2020-2025
John Radcliffe Hospital
2022-2024
German Center for Diabetes Research
2023-2024
TU Dresden
2019-2024
Paul Langerhans Institute Dresden
2024
Helmholtz Zentrum München
2024
King Abdullah University of Science and Technology
2023
Heinrich Heine University Düsseldorf
2023
Deutsches Diabetes-Zentrum e.V.
2023
Center for Systems Biology Dresden
2023
Abstract Canonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that directly contribute forming post-injury scar. Unbiased transcriptomics shows an upregulation collagens both zebrafish mouse following injury. Adoptive transfer macrophages, from either collagen-tagged or adult GFP tpz -collagen donors, enhances scar formation via cell...
Abstract Aims Acute myocardial infarction rapidly increases blood neutrophils (<2 h). Release from bone marrow, in response to chemokine elevation, has been considered their source, but levels peak up 24 h after injury, and neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 min) release of extracellular vesicles (EVs), which have emerged as an important means cell–cell...
Abstract In adult mice, surgically-induced myocardial infarction (MI) activates the cardiac lymphatics, which undergo sprouting angiogenesis, draining interstitial fluid and trafficking macrophages to mediastinal lymph nodes (MLNs), improving function. Given importance of lymphatics post-MI, we investigated their role across neonatal “regenerative window”. At post-natal day 1 (P1) mice fully regenerate heart following MI, in a macrophage-dependent manner, whereas equivalent injury at P7...
Abstract Diabetes causes a range of complications that can affect multiple organs. Hyperglycemia is an important driver diabetes‐associated complications, mediated by biological processes such as dysfunction endothelial cells, fibrosis, and alterations in leukocyte number function. Here, we dissected the transcriptional response key cell types to hyperglycemia across tissues using single‐cell RNA sequencing (scRNA‐seq) identified conserved, well organ‐specific, changes associated with...
Human embryonic stem cells (hESCs) retain the extraordinary capacity to differentiate into different cell types of an adult organism, including pancreatic β-cells. For this particular lineage, although a lot effort has been made in last ten years achieve efficient and reproducible differentiation protocol, it was not until recently that aim roughly accomplished. Besides, several studies evidenced impact resveratrol (RSV) on insulin secretion, even though mechanism by which polyphenol...
In mammalian visceral organs, vascular smooth muscle cells (VSMCs) originate from an epithelial-to-mesenchymal transition (EMT) of embryonic mesothelial (MCs). The ability adult MCs to recapitulate EMT and acquire (SM) markers upon provasculogenic culture suggested they might retain vasculogenic differentiation potential. However, it remains unknown whether MCs-derived SM-like may specific SM lineage the functionality differentiated contractile VSMCs. Here, we describe how a gentle...
Lineage commitment during embryonic stem cell (ESC) differentiation is controlled not only by a gamut of transcription factors but also epigenetic events, mainly histone deacetylation and promoter DNA methylation. The demethylation agent 5′-aza-2′-deoxycytidine (AzadC) has been widely described as an effective cardiomyogenic in various types. However, its toxicity instability complicate use. Therefore, the purpose this study was to examine effects zebularine...
The unlimited expansion of human progenitor cells in vitro could unlock many prospects for regenerative medicine. However, it remains an important challenge as requires the decoupling mechanisms supporting self-renewal and from those promoting their differentiation. This study focuses on pluripotent stem (hPS) cell-derived pancreatic progenitors (PP) to advance novel therapies diabetes. We obtained mechanistic insights into PP requirements identified conditions robust hPS under GMP-compliant...
The unlimited expansion of human progenitor cells in vitro could unlock many prospects for regenerative medicine. However, it remains an important challenge as requires the decoupling mechanisms supporting self-renewal and from those promoting their differentiation. This study focuses on pluripotent stem (hPS) cell-derived pancreatic progenitors (PP) to advance novel therapies diabetes. We obtained mechanistic insights into PP requirements identified conditions robust hPS under GMP-compliant...
Understanding the mechanisms that promote specification of pancreas progenitors and regulate their self-renewal differentiation will help to maintain expand progenitor cells derived from human pluripotent stem (hPS) cells. This improve efficiency current protocols hPS into β-cells bring such closer clinical applications for therapy diabetes. Aldehyde dehydrogenase 1b1 (Aldh1b1) is a mitochondrial enzyme expressed specifically in during mouse development, we have shown its functional...
ABSTRACT The significant advances in the differentiation of human pluripotent stem (hPS) cells into pancreatic endocrine cells, including functional β-cells, have been based on a detailed understanding underlying developmental mechanisms. However, final steps, leading from progenitors to mono-hormonal and mature remain be fully understood this is reflected remaining shortcomings hPS cell-derived islet (SC-islet cells), which include lack β-cell maturation variability among different cell...
Abstract The significant advances in the differentiation of human pluripotent stem (hPS) cells into pancreatic endocrine cells, including functional β-cells, have been based on a detailed understanding underlying developmental mechanisms. However, final steps, leading from progenitors to mono-hormonal and mature remain be fully understood this is reflected remaining shortcomings hPS cell-derived islet (SC-islet cells), which include lack β-cell maturation variability among different cell...
Abstract Background In adult mice, myocardial infarction (MI) activates the cardiac lymphatics, which undergo sprouting angiogenesis (lymphangiogenesis) and function to drain interstitial fluid traffic macrophages mediastinal lymph nodes (MLNs). This prevents oedema reduces inflammatory immune cell content improve function. Purpose Given importance of lymphatics in macrophage clearance after injury, we investigated their role across neonatal "regenerative window". At post-natal day 1 (P1)...
Acute myocardial infarction rapidly increases blood neutrophils (<2 hours). Release of from bone marrow, in response to chemokine elevation, has been considered their source, but levels peak up 24 hours after injury, and neutrophil elevation. This suggests that additional non chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 minutes) release extracellular vesicles (EVs), which are enriched vascular adhesion molecule-1 (VCAM-1)...
Abstract Diabetes causes a range of complications that can affect multiple organs. Hyperglycaemia is an important driver diabetes-associated complications, mediated by biological processes such as dysfunction endothelial cells, fibrosis and alterations in leukocyte number function. Here, we dissected the transcriptional response key cell types to hyperglycaemia across tissues using single-cell RNA-seq (scRNA-seq) identified conserved, well organ-specific, changes associated with diabetes...
Abstract In humans, new-born infants have the ability to regenerate their heart during early life. This is modelled in mouse, where regenerative capacity maintained for first week after birth but lost thereafter. Reactivation of this process holds significant therapeutic potential, however, molecular pathways that might be targeted extend neonatal regeneration remain elusive. Here, we explore a role hypoxia and HIF signalling on regulation epicardial activity which essential development...
ABSTRACT The unlimited expansion of human progenitor cells in vitro could unlock many prospects for regenerative medicine. However, it remains an important challenge as requires the decoupling mechanisms supporting self-renewal and from those promoting their differentiation. This study focuses on pluripotent stem (hPS) cell derived pancreatic progenitors (PP) to advance novel therapies diabetes. We obtained mechanistic insights into PP requirements and, through a hypothesis-driven iterative...
The unlimited expansion of human progenitor cells in vitro could unlock many prospects for regenerative medicine but it remains an important challenge as requires the decoupling mechanisms supporting self-renewal and from feed-forward promoting their differentiation. pluripotent stem (hPS) cell derived pancreatic progenitors (PP) will accelerate development novel therapies diabetes.We obtained mechanistic insights into requirements PP leveraged them to conduct a hypothesis-driven iterative...
The unlimited expansion of human progenitor cells in vitro could unlock many prospects for regenerative medicine. However, it remains an important challenge as requires the decoupling mechanisms supporting self-renewal and from those promoting their differentiation. This study focuses on pluripotent stem (hPS) cell derived pancreatic progenitors (PP) to advance novel therapies diabetes.We obtained mechanistic insights into PP requirements and, through a hypothesis-driven iterative approach,...