Our Science – Rubin Website

Jeffrey S. Rubin, M.D., Ph.D.

Laboratory of Cellular and Molecular Biology Senior Investigator Building 37, Room 2066 37 Convent Dr., MSC 4256 Bethesda, MD 20892-4256 Phone:   301-496-4265 Fax:   301-496-8479 E-Mail:   rubinj@mail.nih.gov

Biography

Dr. Rubin received his M.D. and Ph.D. in molecular biology from Washington University, St. Louis, MO, in 1983. Following an internal medicine residency program at the Jewish Hospital of St. Louis, he joined the Laboratory of Cellular and Molecular Biology at the NCI in 1986 as a biotechnology fellow, where he is now a senior investigator. Dr.Rubin has served as a reviewer for many scientific journals, notably as an editorial board member of the Journal of Biological Chemistry, 1998-2003.

Research

Keratinocyte Growth Factor and Hepatocyte Growth Factor/Scatter Factor

For many years, my research primarily dealt with the purification and biological activities of two heparin-binding mitogens, keratinocyte growth factor (KGF, also known as FGF-7) and hepatocyte growth factor/scatter factor (HGF/SF). These proteins are mediators of mesenchymal-epithelial communication that can stimulate cell migration, differentiation, proliferation and tissue morphogenesis. Through collaborative studies, we explored the role of these factors in development, tissue repair, reproductive tract biology, and neoplasia.

KGF has remarkable cytoprotective effects consistent with the hypothesis that it functions as a homeostatic factor to maintain epithelial barrier function. Palifermin (Kepivance®), a recombinant modified version of KGF, is now being evaluated in clinical trials sponsored by Amgen, Inc. to determine its ability to reduce mucositis that results from chemoradiotherapy. In a phase III clinical trial, palifermin decreased the incidence and duration of severe oral mucositis in patients receiving intensive cancer treatment prior to peripheral blood progenitor cell transplantation for hematologic malignancies. Based on this study, the U.S. Food and Drug Administration approved palifermin for use in this setting. Additional trials are underway to test its safety and efficacy in diminishing severe mucositis in patients treated for solid tumors, such as non-small cell lung cancer as well as head and neck cancer.


Wnt Signaling and Secreted Frizzled-Related Proteins

Currently the major focus of my research is Wnt signaling and a soluble Wnt-binding protein that is homologous to Frizzleds, cell surface Wnt receptors. We demonstrated that this secreted Frizzled-related protein (sFRP-1) binds directly to Wnt protein and modulates its activity. We believe it functions to regulate Wnt-dependent developmental processes and might also have an impact on Wnt signaling in cancer. We have expressed and purified various sFRP family members and sFRP-1 derivatives to study their structure/function properties and biological activity in different contexts. We also have been producing Wnt and Frizzled proteins to facilitate the analysis of sFRP/Wnt/Frizzled interactions and the regulation of Wnt signaling. In addition, we have created an Sfrp1 null mouse model to assess sFRP-1 function in vivo.

With the support of an NCI Intramural Research Award, we used phage display peptide analysis to identify a binding motif for sFRP-1. Although Wnt proteins lack this motif, our results suggest that other proteins possessing such sequences may function as novel binding partners for sFRP-1.

In summary, my work has centered on the discovery and analysis of soluble polypeptide factors involved in the regulation of growth and differentiation. The projects have been highly interactive, involving several collaborations on and off the NIH campus. They have the potential to generate reagents of therapeutic relevance.

Our collaborators include Alan Perantoni, David Salomon and Terry Yamaguchi, NCI; Paul Marker, University of Minnesota Cancer Center; Aykut Uren, Georgetown University Medical Center; Bart Williams, Van Andel Research Institute.

This page was last updated on 6/12/2008.