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Profile
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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
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Year |
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Degree |
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Institution |
1986 |
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Postdoctoral Research Fellow |
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Department of Anatomy, University of Arizona, Tucson, Arizona |
1984 |
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Postdoctoral Research Fellow |
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Department of Biochemistry, University of Arizona, Tucson, Arizona |
1983 |
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Ph.D. - Biology |
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University of California, Los Angeles, California |
1977 |
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B.S. - Biology of Natural Resources; Bioenergetics |
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University of California, Berkeley |
Period |
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Description |
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Organization |
July 2006 - Present |
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Associate Member, Graduate Faculty |
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Department of Cell Biology, Neurobiology & Anatomy, Loyola University, Chicago, Illinois |
June 2005 - Present |
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Adjunct Professor |
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Department of Cell Biology, Neurobiology & Anatomy, Loyola University, Chicago, Illinois |
June 2004 - Present |
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Director: Program in Matrix Biology |
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Children's Memorial Research Center, Chicago, Illinois |
August 1996 - June 2004 |
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Research Scientist |
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Department of Anatomy & Cell Biology, University of Iowa, Iowa City, Iowa |
March 1996 - June 1996 |
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Assitant Professor (Secondary Appointment) |
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Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, Missouri |
June 1994 - June 1996 |
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Assistant Professor (Secondary Appointment) |
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Department of Ophthalmology, St. Louis University School of Medicine, St. Louis, Missouri |
December 1993 - June 1996 |
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Assistant Professor |
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Department of Pediatrics, St. Louis University School of Medicine, St. Louis, Missouri |
December 1991 - November 1993 |
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Research Assistant Professor (Secondary Appointment) |
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Department of Ophthalmology, University of Arizona, Tucson, Arizona |
January 1990 - November 1993 |
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Research Assistant Professor |
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Department of Anatomy, University of Arizona, Tucson, Arizona |
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.
Mary J.C. Hendrix Laboratory; Children's Memorial Research Center
Please see Curriculum Vitae for all publications. (In Press). . .
1986-1989 - National Institutes of Health Cancer Biology Training Grant Fellow
2007 - Present |
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Member, CMRC Microscopy and Imaging Facility User's Group |
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2006 - Present |
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Member, CMRC Information Technology Committee |
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2006 - Present |
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Member, CMRC Genomics Users Group Committee |
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2004 - Present |
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Member, Society for Melanoma Research |
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2004 - Present |
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Member, The Robert H. Lurie Comprehensive Cancer Center of Northwestern University |
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2003 - Present |
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Ad hoc Reviewer, NIH Innovative Technologies for Molecular Analysis of Cancer Program |
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2003 - Present |
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Ad hoc Reviewer, NIH Innovations in Cancer Sample Preparation Program |
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2000 - Present |
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Member, The New York Academy of Sciences |
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2000 - Present |
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Ad hoc Reviewer, NIH SBIR/STTR Grant Applications |
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1999 - Present |
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Reviewer, Scientific Grants for the National Institutes of Health |
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1993 - Present |
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Member, American Association for Cancer Research |
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1990 - Present |
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Member, American Association for the Advancement of Science |
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1990 - Present |
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Member, Metastasis Research Society |
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1989 - Present |
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Member, American Society for Cell Biology |
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2006 - 2007 |
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Member, CMRC Seminar Series Committee |
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2004 - 2006 |
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Chairman, CMRC Information Technology Committee |
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2004 - 2005 |
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Chairman, CMRC FACSAria High Speed Cell Sorter Oversight and Use Committee |
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1997 - 2004 |
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Member, The Holden Comprehensive Cancer Center at The University of Iowa Carver College of Medicine |
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2002 - 2003 |
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Reviewer, Scientific Grants for Cancer Research, UK |
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View Adobe Acrobat PDF file of Richard Seftor's CV.
Last Updated: Aug 7 2007 3:02PM
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