Angiogenesis, or growth of blood vessels, is often suboptimal in many injured tissues such as ischemic tissues following heart attack or diabetic wounds. The healing and regeneration of such tissues critically depend on proper angiogenesis. On the other hand, uncontrolled neovascularization underlies many diseases such as tumor growth, diabetic retinopathy (DR), and age-related macular degeneration (AMD). In addition, capillary destruction is a significant pathological contributor to such diseases as bronchopulmonary dysplasia (BPD) and retinopathy of the prematurity (ROP). At the current state of the knowledge, the molecular mechanisms controlling angiogenesis and vascular integrity are only partially understood, which handicaps efforts to develop effective therapies. In our laboratory, we use both developmental and disease models to understand how these processes are controlled, and explore potential therapeutic approaches.
- Regulation of vascular development by oxygen sensing mechanism. In particular, we generate and use genetically modified mice to understand how the oxygen sensing mechanism regulates vascular development in neonatal retinas.
- Regulation of microvascular integrity. In this project we explore how the oxygen sensing mechanism regulates microvascular stability in diabetic mice and mice exposed to large doses of oxygen.
- Mechanisms of neovascularization in age-related macular degeneration. This is a new project which we are just initiating, and we are interested in understanding the mechanisms underlying neovascularization associated with AMD.
- Role of VEGF signaling in vascular development and stability. The vascular endothelial growth factor is a major inducer of angiogenesis, but it is also required for other aspects of vascular functions. We are interested in defining how each of these individual roles is specified by the same factor.
- Mechanism of vascular regression. Vascular regression is an important aspect for the formation of a healthy vascular system, but the underlying mechanism is poorly understood. We are interested in exploring potential mechanisms.