Donald P. Bottaro, Ph.D.
Dr. Bottaro’s research on the role of epithelial growth factors in the onset and progression of solid tumors began with the discovery of the cell surface receptors for keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF). Later work helped define the structural basis of growth factor-receptor interaction and the role of heparan sulfate proteoglycans as co-receptors. Recent efforts include translating basic knowledge of growth factor signaling to support the development of diagnostic and therapeutic agents that target HGF signaling in genitourinary and other malignancies.
Visit Experimental Cancer Therapeutics Targeting the Hepatocyte Growth Factor/Met Signaling Pathway to view a list of clinical trials for cancer therapeutics targeting the HGF/Met signaling pathway.
1) regulation of epithelial cell growth and motility, 2) cellular and molecular oncogenesis,
4) growth factor inhibitors, 5) biomarker development
Research in Urologic Oncology Branch is aimed at identifying the genetic and biochemical defects that contribute to genitourinary malignancies, and to translating these discoveries into safe and effective treatment strategies. The discovery of germline mutations in the hepatocyte growth factor (HGF) receptor, Met, that predispose affected individuals to papillary renal cell carcinoma (HPRC) type 1, significantly strengthened mounting evidence of the oncogenic potential of this signaling pathway. Normally, HGF stimulates proliferation, motility and morphogenesis in a wide spectrum of cell types, contributing to embryonic development and to tissue repair in adulthood. Abnormal activation of the HGF pathway has been found in many human cancers, including carcinomas of the bladder, breast, colon, liver, lung, kidney and thyroid, sarcomas of bone and muscle, leukemia, lymphoma, glioblastoma and melanoma. In many of these cancers, HGF/Met signaling drives cell invasiveness and tumor metastasis, advancing disease beyond current effective therapies. Understanding the molecular basis of oncogenic signaling and developing strategies for its selective disruption in cancer are our highest priorities.
Selected Key Publications
- Science. 251: 802-4, 1991. [ Journal Article ]
- Nature. 423: 593-5, 2003. [ Journal Article ]
The von Hippel-Lindau tumor suppressor gene product represses oncogenic beta-catenin signaling in renal carcinoma cells.Proc Natl Acad Sci U S A. 103: 14531-6, 2006. [ Journal Article ]
Targeted disruption of heparan sulfate interaction with hepatocyte and vascular endothelial growth factors blocks normal and oncogenic signaling.Cancer Cell. 22: 250-62, 2012. [ Journal Article ]
- J Biol Chem. 289: 20448-61, 2014. [ Journal Article ]
Dr. Bottaro received his B.A. from The University of Chicago and Ph.D. in cellular and molecular biology from Boston University. For his doctoral research he was named Young Investigator of the Year by the American Microcirculatory Society in 1986. He trained as a postdoctoral fellow at Harvard Medical School before joining the NCI's Laboratory of Cellular and Molecular Biology in 1987, where he helped identify keratinocyte growth factor (KGF), hepatocyte growth factor (HGF) and their respective cell surface receptors. In 2003, Dr. Bottaro joined the NCI's Urologic Oncology Branch, where he continues to study growth factor signaling pathways and their subversion in cancer.
|Dinuka de Silva Ph.D.||Postdoctoral Fellow (CRTA)|
|Molly Lee Ph.D.||Postdoctoral Fellow (CRTA)|
|Arpita Roy Ph.D.||Postdoctoral Fellow (CRTA)|