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Michael Klagsbrun

2013 NAVBO Earl P. Benditt Award - Michael Klagsbrun, Harvard Medical School

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Dr. Klagsbrun gave his talk, "FromFGF to neuropilin: Identifying novel regulators of angiogenesis and cancer" via a pre-recorded video. Dr. Patricia D'Amore was on hand at the meeting to accept the award on his behalf.

The NAVBO Meritorious Awards Committee and Council are pleased to announce the selection of Michael Klagsbrun, Ph.D., as the 2013 recipient of the Earl P. Benditt Award, in recognition of his long history of accomplishment in elucidating the role of growth factors in vascular homeostasis and disease. Dr. Klagsbrun will present the Benditt Lecture, "FromFGF to neuropilin: Identifying novel regulators of angiogenesis and cancer," and receive the award, one of NAVBO's highest accolades, at the NAVBO Workshops in Vascular Biology 2013 (October 20-24) in Hyannis, Massachusetts.

Dr. Klagsbrun earned his Ph.D. from the University of Wisconsin-Madison in the laboratory of Robert Bock and pursued post-doctoral training in the Laboratory of Biochemical Pharmacology, in what was then the NIH's Institute of Arthritis, Metabolism, and Digestive Diseases. Following a stint as a staff member at the NIH, he joined the Department of Surgery at Harvard Medical School in 1973 and has remained at that institution ever since, earning the position of Patricia K. Donahoe Professor of Surgery in 2001. Dr. Klagsbrun is currently Senior Associate in Medicine, Vascular Biology Program at Boston Children's Hospital.

Dr. Klagsbrun's laboratory is credited with the first purifications of basic fibroblast growth factor (FGF-2), a potent angiogenic factor, and of heparin-binding EGF-like growth factor (HB-EGF), a potent smooth muscle mitogen. Dr. Klagsbrun's colleagues point to his introduction of heparin-affinity chromatography to the purification of growth factors as a significant accelerator of research into the regulation of cell proliferation in general, and of vascular endothelial mitogenesis in particular.

More recently, the Klagsbrun lab has purified and characterized the neuropilin class of vascular growth
factor receptors that act as novel receptors for members of the VEGF family of angiogenic factor. Neuropilin was originally described as a receptor for semaphorin, a protein involved in regulating axon guidance. These studies have suggested that similar molecular mechanisms regulate angiogenesis and neuronal guidance, both of which are networking processes whose close regulation is essential during prenatal development. This work, published in Cell, yielded landmark findings that have transformed our view of the role of neuropilin in regulating key biological processes. Since that original study, Dr. Klagsbrun and his group have gone on to demonstrate that VEGF binds both neuropilin and VEGFR-2 to form a ternary complex that enhances VEGF's angiogenic activity. His work with neuropilin knockouts in mice and knockdowns in zebrafish was the first to demonstrate the neuropilins are necessary for angiogenesis. These studies have led to the discovery that members of the class-3 semaphorin family of axon guidance mediators actually inhibit angiogenesis.

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In the realm of the EGF receptor family of proteins, Dr. Klagsbrun and his group have found that tumor endothelial cells, unlike normal endothelial cells, express ERbB1 and that EGFR KI inhibits tumor growth partly by blocking tumor endothelial EGFR activity. These studies suggest that it may, in fact, be possible to target tumor blood vessels without affecting the normal vasculature, a finding with significant therapeutic importance.

To quote from a letter of nomination: "It is my opinion that the field of vascular biology would be ten years behind its present accomplishments had it not been for the pioneering and continuing work of Dr. Michael Klagsbrun. ... with nearly 300 publications, many in the very best journals, and the clear credit for developing several new areas within the field of vascular biology, Dr. Klagsbrun's accomplishments should not be underestimated. He is a true pioneer, a creative thinker, a rigorous scientist and one of the great lights of our field."

Compiled by William R. Huckle,
NAVBO Editor

Read more about the Benditt Award

Read more about Dr. Klagsbrun's research