Donald P. Bottaro, PhD
Donald P. Bottaro, Ph.D., Adjunct Professor
Dr. Bottaro is an Adjunct Professor at the Institute for Regenerative Medicine and a Senior Scientist in the Urologic Oncology Branch at the National Cancer Institute (NCI) in Bethesda, Maryland. He received his PhD from Boston University and was a postdoctoral fellow at Harvard Medical School. At NCI, he helped discover keratinocyte growth factor, hepatocyte growth factor and their cell surface receptors. Later work defined structure-function relationships in these proteins and established the importance of extracellular matrix in receptor activation. This work has proven to be relevant to both oncogenic signaling in cancer as well as physiologic signaling in regenerative medicine. SYNOPSIS OF AREA OF INTEREST:
Dr. Bottaro’s current research is focused on growth factor signaling in heritable forms of kidney cancer, where genetic insights have enabled the rapid identification of specific intracellular networks that contribute to oncogenesis, tumor progression and metastasis. Remarkably, many of these signaling pathways are also essential for normal embryological development as well as tissue repair and regeneration. DETAILED AREA OF INTEREST:
For 20 years, Dr. Bottaro has studied the basic biology of growth factor signaling. In collaboration with Dr. Terry Burke at the NCI, structural analysis of a specific intracellular mediator of hepatocyte growth factor activity enabled the design and development of small synthetic binding antagonists with utility as research tools and potential as anti-cancer drugs. Together, Drs. Bottaro and Burke have identified selective antagonists with nanomolar potency that inhibit growth factor-stimulated cancer cell invasion and tumor metastasis in animal models. With another NCI collaborator, Dr. Andy Byrd, the first three-dimensional structures of the hepatocyte growth factor protein were obtained. Drs. Bottaro and Byrd then used this information as the basis for the rational design of proteins capable of antagonizing the aberrant growth factor signaling frequently observed in cancer, and others optimized for systemic delivery in regenerative medicine applications. These studies demonstrated clearly that extracellular matrix components have critical roles in growth factor signaling that could be exploited to develop novel therapeutic strategies.
Noting the emerging importance of extracellular matrix components for the regulation of cell function and its particular relevance to the fields of regenerative medicine and tissue engineering, Drs. Mohammad Heidaran, Shu Chien and Donald Bottaro founded the Gordon Research Conference on Signal Transduction by Engineered Extracellular Matrices in 2000. This biannual meeting was designed to bridge communication gaps between the wide range of professions that contribute to progress in tissue engineering, to foster the development of enduring interactions between physical and biological scientists, and to expose students and young professionals to the latest and most important ideas, issues and opportunities at the confluence of molecular and cellular biology and tissue engineering. To accomplish these goals, the conference focuses on how environmental cues such as mechanical stress, soluble factors and the extracellular matrix regulate intracellular signaling networks to affect cell adhesion, migration, growth and differentiation in contexts relevant to regenerative medicine. After its first decade, the conference continues to provide a collegial forum for exchanging the latest scientific breakthroughs among a diverse group of talented scientists.