Publications

The role of PHD2 in breast cancer metastasis

Targeting endothelial metabolism for anti-angiogenesis therapy: A pharmacological perspective

Regulation of Protein kinase D2 by Hsp is crucial for tumour cell-endothelial cell communication in gastrointestinal tumours

Endothelial Growth Factor B Endothelial Fatty Acid Transport: Role of Vascular

The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade during HER2-Positive Breast Cancer Progression

Gene prioritization through genomic data fusion

Novel roles of plasmin, uPAR and suPAR in mobilization and retention of HSC/HPCs

Generation of monoclonal antibodies against autologous proteins in gene-inactivated mice

Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions

Metabolic Pathways Fueling the Endothelial Cell Drive

Endothelial cell (EC) metabolism is important for health and disease. Metabolic pathways, such as glycolysis, fatty acid oxidation, and amino acid metabolism, determine vasculature formation. These metabolic pathways have different roles in securing the production of energy and biomass and the maintenance of redox homeostasis in vascular migratory tip cells, proliferating stalk cells, and quiescent phalanx cells, respectively. Emerging evidence demonstrates that perturbation of EC metabolism results in EC dysfunction and vascular pathologies. Here, we summarize recent insights into EC metabolic pathways and their deregulation in vascular diseases. We further discuss the therapeutic implications of targeting EC metabolism in various pathologies.

348 Effect of propranolol on heart rate and arrhythmias in freely moving mice and isolated hearts of deltaKPQ-SCN5A LQT3 mice

Increased cardiac expression of TIMP-1 and TIMP-2 is related to cardiac fibrosis and dysfunction in the chronic pressure-overloaded human heart

Guidance of Vascular and Neuronal Network Formation

Stroma Formation and Angiogenesis by Overexpression of Growth Factors, Cytokines, and Proteolytic Enzymes in Human Skin Grafted to SCID Mice

Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development

GAS6 and AXL Promote Insulin Resistance by Rewiring Insulin Signaling and Increasing Insulin Receptor Trafficking to Endosomes

Growth arrest–specific 6 (GAS6) is a secreted protein that acts as a ligand for TAM receptors (TYRO3, AXL, and MERTK). In humans, GAS6 circulating levels and genetic variations in GAS6 are associated with hyperglycemia and increased risk of type 2 diabetes. However, the mechanisms by which GAS6 influences glucose metabolism are not understood. Here, we show that Gas6 deficiency in mice increases insulin sensitivity and protects from diet-induced insulin resistance. Conversely, increasing GAS6 circulating levels is sufficient to reduce insulin sensitivity in vivo. GAS6 inhibits the activation of the insulin receptor (IR) and reduces insulin response in muscle cells in vitro and in vivo. Mechanistically, AXL and IR form a complex, while GAS6 reprograms signaling pathways downstream of IR. This results in increased IR endocytosis following insulin treatment. This study contributes to a better understanding of the cellular and molecular mechanisms by which GAS6 and AXL influence insulin sensitivity. Article Highlights

Engineering Vascularized Bone: Osteogenic and Proangiogenic Potential of Murine Periosteal Cells

One of the key challenges in bone tissue engineering is the timely formation of blood vessels that promote the survival of the implanted cells in the construct. Fracture healing largely depends on the presence of an intact periosteum but it is still unknown whether periosteum-derived cells (PDC) are critical for bone repair only by promoting bone formation or also by inducing neovascularization. We first established a protocol to specifically isolate murine PDC (mPDC) from long bones of adult mice. Mesenchymal stem cells were abundantly present in this cell population as more than 50% of the mPDC expressed mesenchymal markers (CD73, CD90, CD105, and stem cell antigen-1) and the cells exhibited trilineage differentiation potential (chondrogenic, osteogenic, and adipogenic). When transplanted on a collagen-calcium phosphate scaffold in vivo, mPDC attracted numerous blood vessels and formed mature bone which comprises a hematopoiesis-supportive stroma. We explored the proangiogenic properties of mPDC using in vitro culture systems and showed that mPDC promote the survival and proliferation of endothelial cells through the production of vascular endothelial growth factor. Coimplantation with endothelial cells demonstrated that mPDC can enhance vasculogenesis by adapting a pericyte-like phenotype, in addition to their ability to stimulate blood vessel ingrowth from the host. In conclusion, these findings demonstrate that periosteal cells contribute to fracture repair, not only through their strong osteogenic potential but also through their proangiogenic features and thus provide an ideal cell source for bone regeneration therapies.

Mice lacking factor VII develop normally but suffer fatal perinatal bleeding