CMRC Children's Memorial Research Center
Profile


Richard E.B. Seftor
 Director: Program in Matrix Biology



Children's Memorial Research Center
2300 Children's Plaza, Box 222 Room 476
Chicago, IL 60614
Phone: (773) 755-6377


Education
Year Degree Institution
1986 Postdoctoral Research Fellow Department of Anatomy, University of Arizona, Tucson, Arizona
1984 Postdoctoral Research Fellow Department of Biochemistry, University of Arizona, Tucson, Arizona
1983 Ph.D. - Biology University of California, Los Angeles, California
1977 B.S. - Biology of Natural Resources; Bioenergetics University of California, Berkeley

Work Experience
Period Description Organization
July 2006 - Present Associate Member, Graduate Faculty Department of Cell Biology, Neurobiology & Anatomy, Loyola University, Chicago, Illinois
June 2005 - Present Adjunct Professor Department of Cell Biology, Neurobiology & Anatomy, Loyola University, Chicago, Illinois
June 2004 - Present Director: Program in Matrix Biology Children's Memorial Research Center, Chicago, Illinois
August 1996 - June 2004 Research Scientist Department of Anatomy & Cell Biology, University of Iowa, Iowa City, Iowa
March 1996 - June 1996 Assitant Professor (Secondary Appointment) Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, Missouri
June 1994 - June 1996 Assistant Professor (Secondary Appointment) Department of Ophthalmology, St. Louis University School of Medicine, St. Louis, Missouri
December 1993 - June 1996 Assistant Professor Department of Pediatrics, St. Louis University School of Medicine, St. Louis, Missouri
December 1991 - November 1993 Research Assistant Professor (Secondary Appointment) Department of Ophthalmology, University of Arizona, Tucson, Arizona
January 1990 - November 1993 Research Assistant Professor Department of Anatomy, University of Arizona, Tucson, Arizona

Research Interests
A major focus of our research is the examination of tumor cell/extracellular matrix interactions that contribute to the invasive and/or metastatic processes associated with cancer progression. Recently, microarray gene chip analyses of highly compared to poorly aggressive melanoma cells identified an increase in the expression of certain genes with the aggressive, vasculogenic mimicry phenotype demonstrated by aggressive melanoma cells. Vasculogenic mimicry describes a process where aggressive tumor cells in three-dimensional matrices mimic embryonic vasculogenesis by forming extracellular matrix-rich, patterned tubular networks. Microarray analyses revealed a significant increase in the expression of laminin 5 (Ln-5 gamma 2 chain), and matrix metalloproteinases (MMP)-1, -2, -9 and MT1-MMP (MMP-14) in aggressive compared to poorly aggressive melanoma cells. These components were found to co-localize with developing patterned networks, and antisense oligonucleotides to the Ln-5 gamma 2 chain (but not sense oligonucleotides), and antibodies to MMP-2 or MT1-MMP (but not MMP-9) inhibited the formation of these networks. Cultures which did not receive antibodies to either MMPs-2 or -14 were found to contain the Ln-5 gamma 2 chain promigratory cleavage fragments. A significant observation from these studies was that poorly aggressive melanoma cells seeded on a three-dimensional matrix pre-conditioned by the aggressive cells formed tubular networks along the Ln-5 gamma 2 chain-enriched tracks deposited into the matrix by the aggressive cells. These results suggest that increased expression of MMP-2 and MT1-MMP, along with deposition of the Ln-5 gamma 2 chain and/or its cleavage fragments into the tumor cells’ microenvironment, are required for vasculogenic mimicry by aggressive melanoma cells. Furthermore, generation of laminin-rich, patterned networks by aggressive melanoma tumor cells in three-dimensional culture appears to recapitulate the networks observed in aggressive melanoma patients’ tissue sections. These results suggest that culturing aggressive tumor cells in three-dimensional matrices may serve as a model to help identify specific molecular targets that could function as templates for the coordinated migration of aggressive tumor cells and the proteolytic remodeling of their extracellular microenvironment, and may lead to profound implications for the development of novel therapies directed at the extracellular matrix to alter tumor progression.

Lab Affiliations
Mary J.C. Hendrix Laboratory; Children's Memorial Research Center
Recent Publications
Please see Curriculum Vitae for all publications. (In Press). . .

Awards/Honors
1986-1989 - National Institutes of Health Cancer Biology Training Grant Fellow

Professional Service
2007 - Present Member, CMRC Microscopy and Imaging Facility User's Group
2006 - Present Member, CMRC Information Technology Committee
2006 - Present Member, CMRC Genomics Users Group Committee
2004 - Present Member, Society for Melanoma Research
2004 - Present Member, The Robert H. Lurie Comprehensive Cancer Center of Northwestern University
2003 - Present Ad hoc Reviewer, NIH Innovative Technologies for Molecular Analysis of Cancer Program
2003 - Present Ad hoc Reviewer, NIH Innovations in Cancer Sample Preparation Program
2000 - Present Member, The New York Academy of Sciences
2000 - Present Ad hoc Reviewer, NIH SBIR/STTR Grant Applications
1999 - Present Reviewer, Scientific Grants for the National Institutes of Health
1993 - Present Member, American Association for Cancer Research
1990 - Present Member, American Association for the Advancement of Science
1990 - Present Member, Metastasis Research Society
1989 - Present Member, American Society for Cell Biology
2006 - 2007 Member, CMRC Seminar Series Committee
2004 - 2006 Chairman, CMRC Information Technology Committee
2004 - 2005 Chairman, CMRC FACSAria High Speed Cell Sorter Oversight and Use Committee
1997 - 2004 Member, The Holden Comprehensive Cancer Center at The University of Iowa Carver College of Medicine
2002 - 2003 Reviewer, Scientific Grants for Cancer Research, UK

Curriculum Vitae
Adobe Acrobat PDF View Adobe Acrobat PDF file of Richard Seftor's CV.

Last Updated: Aug 7 2007 3:02PM

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