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Derrick Brazill, Associate Professor of Biology |
Education:
- Postdoc. 1995-1999, Rice University
- Ph.D. 1995, University of California, Berkeley
- B.S. 1989, Stanford University
Research Interest:
Extracellular Factors Regulating Cell Behavior
Proteins in human serum constantly bombard our cells with numerous signals, telling them to grow, multiply, differentiate or die. These signals must be properly integrated by the cells in order to ensure the health of the individual. Loss of regulation can lead to defects and diseases including metastatic cancer and atherosclerosis. Our lab is specifically interested in how these signals regulate the cytoskeleton. Unfortunately, the sheer number of players involved in signaling to the cytoskeleton creates an unwieldy morass of interconnected proteins, making the process difficult to study. We therefore study the role of extracellular factors in regulating cell behavior in the simple eukaryote Dictyostelium discoideum. As an NIH model system, Dictyostelium offers a variety of advantages in including its ease of growth, its conservation of mammalian signaling pathways and its genetic tractability.
Dictyostelium normally exist as vegetative amoebae that feed on bacteria and multiply by fission. When the amoebae overgrow their food source and begin to starve, they aggregate using relayed pulses of cAMP as a chemoattractant, eventually forming a multicellular fruiting body. The entire process takes 24 hours, but will not begin unless the density of starving cells is high enough to allow formation of an appropriately sized fruiting body. The ability to develop is regulated by an extracellular protein called CMF, which starving cells secrete. Only when the cells are at a high density, as determined by high levels of CMF, will the cells initiate development. We study the signal transduction pathways activated by CMF and how they impact other developmental pathways. We have found that CMF regulates development by modulating the cell's cytoskeleton, as well as its ability to respond to cAMP. Specifically, we’ve been looking at how CMF controls signaling by G proteins, protein kinases, phospholipase D and paxillin, all of which have human homologs.
While continuing our work on Dictyostelium, we’ve expanded our studies to include cancer cells. Phospholipase D and paxillin, two proteins which CMF uses to regulate Dictyostelium cells, are also involved in cancer metastasis in mammalian. Using what we have learned in Dictyostelium, we are examining how serum proteins use paxillin and phospholipase D to regulate the cytoskeleton, and thus metastasis.
Selected Publications:
- Pribic J, Garcia R, Kong M, Brazill D. Paxillin and phospholipase D interact to regulate actin-based processes in Dictyostelium discoideum. Eukaryot Cell. 2011 Jul;10(7):977-84. Epub 2011 Apr 29.
- Gomer RH, Jang W, Brazill D. Cell density sensing and size determination. Dev Growth Differ. 2011 May;53(4):482-94.
- Ray S, Chen Y, Ayoung J, Hanna R, Brazill D. Phospholipase D controls Dictyostelium development by regulating G protein signaling.Cell Signal. 2011 Feb;23(2):335-43.
- Duran, M.B., Rahman, A., Colten, M., Brazill, D. (2009) Dictyostelium discoideum Paxillin Regulates Actin-Based Processes. Protist 160(2):221-32
- Deenadayalan, B., Brazill, D. Gomer, R., H., Eichinger, L., Rivero, F., Noegel, A., A. (2007) An unusual G protein coupled receptor mediates cell density sensing in Dictyostelium. Current Biology, 17(10):
- Brazill, D. and Gomer, R.H. (2008) Brazill, "A eukaryotic neighbor: Dictyostelium discoideum." Myxobacteria: Multicellularity and Differentiation (2008) : 439-452.
- Thomason, P., A., Brazill, D., T and Cox, E., C.(2006) A Series of Dictyostelium Expression Vectors for Use With Recombination Cloning. Plasmid 56(3): 142 – 152
- Chen. Y.., Rodrick, V., Yan, Y., Brazill, D. (2005) PldB, a Phospholipase D Homologue in Dictyostelium discoideum mediates quorum sensing during development. Euk Cell. 4: 694-702.
- Gomer, R.H. and Brazill, D.T. (2003) The versatile Dictyostelium discoideum. Meeting Report: International Dictyostelium Conference 2002. Protist 154, 11-16.
- Bishop, J.D., Moon, B.C., Ratner, D., Dottin, R.P., Gomer, R.H., Brazill, D.T. (2002) A second UDP-glucose pyrophosphorylase is required for differentiation and development in Dictyostelium discoideum. J Biol Chem 277:32430-32437.
- Azhar, M., Kennady, PK., Pande, G., Espiritu, M., Holloman, W., Brazill, D., Gomer, RH., Nanjundiah, V. Cell cycle phase, cellular Ca2+ and development in Dictyostelium discoideum. Int J Dev Biol. 2001 Apr;45(2):405-14.
- Brazill, D.T., Meyer, L.R., Diane Hatton, Debra A. Brock, Gomer, R.H. (2001) ABC transporters required for endocytosis and endosomal pH regulation in Dictyostelium J Cell Sci. 2001 Nov 1;114(Pt 21):3923-3932.
- Brazill, D.T.,Lindsey, D.F., Bishop, J.D., and Gomer, R.H. (1998) Cell-density sensing mediated by a G-protein-coupled receptor activating phospholipase C. J Biol Chem. 273, 8161-8168.
- Brazill, D.T., Gundersen, R. and Gomer, R.H. (1997) A cell-density sensing factor regulates the lifetime of a chemoattractant-induced Ga-GTP conformation. FEBS Letters 404, 100-104.
- Jain, R., Brazill, D.T., Cardelli, J.T., Bush, J., and Gomer, R.H. (1997) Autocrine factors controlling early development. In Dictyostelium-A Model System for Cell and Developmental Biology. (Y. Maeda, K. Inouye, and I. Takeuchi, Eds.) Universal Academy Press, Inc., Tokyo, Japan. pp. 219-234.
- Chen. Y.., Rodrick, V., Yan, Y., Brazill, D. (2005) PldB, a Phospholipase D Homologue in Dictyostelium discoideum mediates quorum sensing during development.