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Tissue Growth and Repair


 Napoleone Ferrara

Napoleone Ferrara,
Genentech Fellow
In the past, blood vessels were considered to be a simple system of conduits that did little more than provide oxygen and nutrients to maintain cellular functions within different tissues. Recent studies of the biochemistry and cell biology of the vessel wall, however, have dramatically extended the role of the vasculature, which is now believed to directly regulate the development and function of certain organs. Thus, the identification and characterization of the genes that govern vascular functions within various organs may be beneficial for the treatment of disease processes. This redefinition and expansion of the role of the vasculature has helped the field of vascular biology evolve into a distinct discipline with its own set of unique scientific questions and its own potential for important translational research projects.

In 1989, Dr. Napoleone Ferrara and his team at Genentech identified vascular endothelial growth factor (VEGF) as a major regulator of vascular functions. Since then, his team has further characterized VEGF as a key player in a broad variety of biological processes, including embryonic development, reproductive functions, growth of the long bones in the body, and the generation of blood cells. In addition, his team has demonstrated that VEGF is a key mediator of tumor angiogenesis, or blood vessel growth, and that interference with VEGF activity by means of a neutralizing antibody can reduce tumor growth. Studies on the role of VEGF in blood vessel formation in the retina initiated clinical development of an anti-VEGF antibody fragment, Lucentis® (ranibizumab injection), as a therapy for degenerative eye disease. In June 2006, Lucentis was approved by the FDA for the treatment of neovascular (wet) age-related macular degeneration (AMD).

Angiogenesis and the Vessel Wall Angiogenesis and the Vessel Wall

Currently, scientists at Genentech are not only studying the effects of inhibiting VEGF but also the effects of increasing VEGF levels in a host of different medical conditions, including bone repair, wound healing and treatment after a heart attack. In addition, a group of researchers is investigating whether increased VEGF levels are implicated in the progression of inflammatory diseases involving the vasculature, such as artheriosclerosis and arthritis.

Another highly innovative area of research at Genentech focuses on the identification of novel tissue-specific factors that regulate the blood supply or vascular function of particular organ systems. Although vascular cells are an integral part of all tissues, they may differ molecularly and functionally between different tissues. Ferrara and his team recently identified the endocrine gland vascular endothelial growth factor (EG-VEGF), which regulates blood vessel formation in endocrine tissues exclusively. This groundbreaking approach of identifying tissue-specific angiogenic factors holds promise for the development of therapeutic strategies that may activate local angiogenesis and thus avoid some of the potential side effects of systemic angiogenic therapy.

Today, research in tissue growth and repair represents a wide-ranging and exciting research direction for Genentech, with a large number of scientists in different departments working to better understand the role of the vasculature in a range of tissues and organ systems.