The Brekken laboratory is located in the Hamon Center for Therapeutic Oncology Research and studies tumor - host interactions with a particular emphasis on extracellular matrix (ECM) and angiogenesis. The function of matricellular proteins and the biology of anti-cancer therapy are the central areas of focus for the lab. The lab studies how angiogenesis and ECM remodeling are key components of the tumor microenvironment. Current projects are focused on the function of matricellular proteins (e.g., SPARC and fibulin-5) as regulators of ECM remodeling and angiogenesis.
Another major area of study in the lab is the development and evaluation of novel therapy for cancer with a particular focus on anti-angiogenic strategies. Vascular endothelial growth factor (VEGF) is a primary stimulant of blood vessel growth in tumors and as such is a relevant target for anti-angiogenic intervention. Currently we are studying the mechanism of anti-VEGF therapy and how inhibition of VEGF activity affects the tumor microenvironment.
RESEARCH INTERESTS
Angiogenesis
Cancer Therapy
Extracellular Matrix
Metastasis
Tumor Microenvironment
RECENT PUBLICATIONS
Arnold SA, Rivera LB, Miller AF, Carbon JG, Dineen SP, Xie Y, Castrillon DH, Sage EH, Puolakkainen P, Bradshaw AD, Brekken RA., "Lack of host SPARC enhances vascular function and tumor spread in an orthotopic murine model of pancreatic carcinoma" Disease Models and Mechanisms, PMID: 20007485, January 2010
Roland CL, Lynn KD, Toombs JE, Dineen SP, Udugamasooriya DG, Brekken RA, "Cytokine levels correlate with immune cell infiltration after anti-VEGF therapy in preclinical mouse models of breast cancer." PLoS One, PMID: 19888452, November 2009
Roland CL, Dineen SP, Lynn KD, Sullivan LA, Dellinger MT, Sadegh L, Sullivan JP, Shames DS, Brekken RA., "Inhibition of vascular endothelial growth factor reduces angiogenesis and modulates immune cell infiltration of orthotopic breast cancer xenografts." Molecular Cancer Therapeutics, PMID: 19567820, July 2009
Udugamasooriya et al, "A peptoid antibody surrogate that antagonizes VEGF receptor 2 activity" J. Am. Chem. Soc., 130:5744-5752, February 2008
Arnold SA, Brekken RA., "SPARC: a matricellular regulator of tumorigenesis." J Cell Commun Signal, PMID: 19809893, October 2009
SIGNIFICANT PUBLICATIONS
Brekken, R.A., Huang, X., King, S.K., and Thorpe, P.E., "Vascular endothelial growth factor as a marker of tumor endothelium." Cancer Research, 58:1952 - 1959, 1998
Bergers, G., Brekken, R., Vu, T.H., Itoh, T., Tamaki, K., Tanazawa, K., Thorpe, P., Itohara, S., Werb, Z., and Hanahan, D., "Gelatinase B triggers the angiogenic switch during carcinogenesis." Nature Cell Biology, 2:737 - 744, 2000
Brekken, R.A., Overholser, J.P., Stastny, V.A., Waltenberger, J., Minna, J.D., and Thorpe, P.E., "Selective inhibition of VEGFR2 activity by a monoclonal anti - VEGF antibody blocks tumor growth in mice." Cancer Research, 60:5117 - 5124, 2000
Puolakkainen*, P., Brekken*, R. A., Muneer, S., and Sage, E. H., "Enhanced growth of pancreatic tumors in SPARC-null mice is associated with decreased deposition of extracellular matrix and reduced tumor cell apoptosis" Molecular Cancer Research, 2:215-224, May 2004
Dineen SP, Lynn KD, Holloway SE, Miller AF, Sullivan JP, Shames DS, Beck AW, Barnett CC, Fleming JB, Brekken RA., "Vascular endothelial growth factor receptor 2 mediates macrophage infiltration into orthotopic pancreatic tumors in mice." Cancer Research, PMID: 18519694, June 2008
Point and right click (click and hold for Mac users) your mouse onand select "Save this link (or target) as..." option to save the file to your local computer.
