Grants and Contracts Details
The abnormal growth of blood vessels, known as pathological angiogenesis, drives over 70 diseases that affect over 500 million people worldwide (Carmeliet. Nature 2005). Principal among these are arthritis, atherosclerosis, cancer, diabetes, and age-related macular degeneration (AMD). From cradle to grave, the leading causes of blindness also have as a common culprit pathological angiogenesis. Retinopathy of prematurity, diabetic retinopathy, corneal injury/infection, and AMD all rob vision by stimulating aberrant blood vessel growth Therapies for all these scourges are extremely unsatisfying due, in large part, to insufficient insight into their pathobiology. Our laboratory focuses on broad aspects of ocular vascular biology in an effort to develop novel therapies for blinding diseases. We believe that effective translation from the bench to the bedside is impossible without the solid foundation of basic science, guided by a firm mechanistic understanding of their pathogeneses. There are three major areas of focus in my laboratory whose progress would be accelerated and stimulated by an RPB Senior Scientific Investigator Award. The first is our study of the mechanisms of action of small interfering RNA (siRNA) that is independent of RNA interference. A second area of focus is the development of novel diagnostic and therapeutic tools for AMD. Recently we published an Article in Nature that reported that the chemokine receptor CCR3 is specifically expressed in human choroidal endothelial cells in vivo only in human donor eyes with CNV due to AMD. The third focus area is the identification of endogenous angiogenesis modulators. Using the avascular and alymphatic cornea as a model discovery system, we demonstrated that sVEGFR 1 was singularly essential for corneal avascularity (Nature 2006), and also recently discovered a novel molecule called sVEGFR-2 that it is singularly critical for the development of an alymphatic cornea (Nature Medicine 2009). The scaffolding of our studies is the use of multiple experimental platforms such as molecular, biochemical, and transgenic techniques to achieve our objectives of defining the mechanistic principles governing fundamental biological processes in the eye and translating this information into clinically valuable diagnostic and therapeutic tools.
|Effective start/end date||1/1/10 → 12/31/10|
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