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Five UCSF Scientists Elected to National Academy of Sciences
Date:5/4/2009

f cancers and to identify therapeutic strategies.

In the mid 1980s, Hanahan produced some of the first 'oncomice' - mice genetically engineered to develop organ-specific human cancers. He has used the models to investigate the multi-stage pathways that govern tumor formation and progression, and to explore the benefits of targeted therapies, in particular strategies aimed at blocking the growth of blood vessels to tumors, which rely on the blood supply for growth. This approach is known as angiogenesis inhibition.

He discovered, in collaboration with the late Judah Folkman at Harvard Medical School, the "angiogenic switch," which is activated to produce new blood vessels in early stage lesions preceding overt tumors. A current focus of his work is elucidating the "organ of genesis" of tumors, in which multiple cell types assemble with overtly transformed cells to form aberrant, expansive microenvironments of cancer.

Most recently, he and UCSF colleague Gabriele Bergers, PhD reported evidence that angiogenesis inhibitors -- drugs designed to starve tumors or their blood supply -- succeed at first, but then promote more invasive cancer growth in animals. This provocative finding, he says, warrants further study in model systems and in humans to elucidate mechanisms that could in turn lead to strategies for harnessing the drugs more effectively.

He has also used genetically engineered mouse models to investigate mechanisms of self tolerance to the pancreatic beta cells, which are destroyed by the immune system in type I diabetes; he found, for example rare tolerance-inducing cells in the thymus that express the beta-cell specific insulin gene.

As a graduate student, Hanahan developed high efficiency plasmid transformation methods and E. coli strains that have facilitated DNA cloning procedures; his work on E. coli transformation (the production of "competent cells") has facilitated molecular gen
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