1. Signaling in cerebral cavernous malformation:
Cerebral cavernous malformation (CCM) is a cerebral vascular disease that affects 200,000 individuals in the US. It is both an inherited disease and an acquired disease, in both cases resulting from loss of the CCM protein complex in brain endothelial cells. The lab has identified increased MEKK3-KLF2/4 signaling, ADAMTS5/versican, and other pathways as the basis for this disease. Rotation projects are available to investigate how these and other signaling mechanisms contribute to CCM lesion formation using both mouse models and human patients.
2. Fluid shear forces in cardiovascular development and disease:
An intrinsic aspect of the heart and vasculature is that their function is linked to physical forces associated with the movement of blood or lymph. Fluid forces are believed to play central roles in the development of the heart, blood vessels and even lymphatic vessels, but the molecular and cellular pathways by which they do so have remained mysterious. The lab is presently investigating a number of endothelial signaling pathways that are responsible for valve development and vascular development and remodeling in the blood and lymphatic systems. These studies combine ex vivo flow chambers to study primary endothelial cells and mouse models to study vessel development and function in vivo. Rotation projects are presently available to study the role of KLF2 signaling in response to fluid shear during valve development and novel links between hemodynamic forces and vascular diseases in the arterial and venous system.
3. Lymphatic vascular development and biology:
Although largely forgotten for almost a century, the lymphatic vascular system is essential for many aspects of vertebrate life and a major player in many human diseases, including both cardiovascular disease and cancer. Our lab investigates a number of signaling pathways and cellular responses essential for lymphatic vascular development and function, including a specialized platelet receptor (CLEC2) the mediates lympho-venous hemostasis at sites of connection between the lymphatic and blood vasculatures and specialized signaling pathways (VEGF-C/VEGFR3) by which lymphatic vessels grow. Rotation projects are presently available in both of these areas and in the new area of organ-specific lymphatic function using mouse genetic models and endothelial cell studies ex vivo.
4. Vascular signaling in hematopoiesis and hemostasis:
Although blood cells are produced in the bone marrow after birth, prior to birth blood cell production takes place in several sites, including the yolk sac, arterial vasculature, and fetal liver. Our lab has identified unexpected roles for VEGF-C and other endothelial signaling pathways in embryonic hematopoiesis. We have also identified novel roles for endothelial cells in regulating hemostasis in vivo. Rotation projects are available to investigate how VEGF-C and other pathways control embryonic hematopoiesis, and the endothelium provides spatial and temporal regulation of hemostasis.