359 Biotechnology Building
Professor of Cell Biology
Bill Brown is a Professor of Cell Biology in the Department of Molecular Biology and Genetics, and he is a member of the Graduate Field of Biochemistry, Molecular and Cell Biology. He received his Ph.D. in Medical Sciences from the University of Texas Southwestern Medical Center at Dallas in 1981, where he worked with Bill Snell. After that he was a Postdoctoral Fellow in cell biology with Marilyn Farquhar at Yale University School of Medicine from 1981 to 1985. In 1985, he joined the faculty at Cornell. He was a Visiting Scientist at the Scripps Research Institute in 2003.
Our general research interests are in the area of eukaryotic cell biology but with a common theme of the role of lipid modifying enzymes in organelle biology. The first project focuses on the cellular and molecular mechanisms of intracellular membrane trafficking in the secretory and endocytic pathways. We are examining the role that phospholipid-modifying enzymes (phospholipases and lysophospholipid acyltransferases) play in the formation of membrane tubules from the Golgi complex and endosomes. These membrane tubules appear to facilitate membrane trafficking from both the Golgi complex and endosomes. The second project is on the cellular and molecular mechanisms of lipid (fat) storage and utilization within organelles called lipid droplets (also called adiposomes). Excess fats are converted to triglycerides (TGs) and then stored in lipid droplets, which are highly dynamic intracellular organelles conserved from yeast to humans. When the chemical energy stored in TGs is needed by cells, lipolysis is triggered to breakdown TGs and lipid droplets. We are currently engaged in a project to better understand TG hydrolysis, which is catalyzed by newly discovered family of neutral lipases, the Patatin Domain Containing Phospholipase A (PNPLA) enzymes. Storage and utilization of excess fats in lipid droplets has direct relevance to our understanding of obesity and diabetes.
Click here to view Dr. Brown's PubMed listings.
de Figueiredo, P., R. S. Polizotto, D. Drecktrah, and W. J. Brown. 1999. Membrane tubule-mediated reassembly and maintenance of the Golgi complex is disrupted by phospholipase A2 antagonists. Mol. Biol. Cell 10:1763-1782.
Polizotto, R. S., P. de Figueiredo and W. J. Brown. 1999. Stimulation of Golgi membrane tubulation and retrograde trafficking to the ER by Phospholipase A2 Activating Protein (PLAP) peptide. J. Cell. Biochem. 74:670-683.
Drecktrah, D., and W. J. Brown. 1999. Phospholipase A2 antagonists inhibit nocodazole-induced Golgi mini-stack formation: evidence for an ER-intermediate and constitutive recycling. Mol. Biol. Cell. 10:4021-4032.
de Figueiredo, P. and W. J. Brown. 1999. Clofibrate Inhibits Membrane Trafficking to the Golgi Complex and Induces its Retrograde Movement to the Endoplasmic Reticulum. Cell Biol. & Toxicol. 15: 311-323.
de Figueiredo, P., Drecktrah, D. R. S. Polizotto, N. Cole, J. Lippincott-Schwartz, and W. J. Brown. 2000. Phospholipase A2 antagonists inhibit constitutive retrograde membrane trafficking from the Golgi complex and TGN to the ER. Traffic 1:504-511.
de Figueiredo, P., R. S. Polizotto, D. Drecktrah, S. A. Wood, M. Banta and W. J. Brown. 2001. Inhibition of endosome tubulation and receptor recycling by phospholipase A2 (PLA2) antagonists suggests a general role for PLA2 in tubule-mediated membrane trafficking. J. Biol. Chem. 276:47361-47370.
Drecktrah, D., K. Chambers, E. L. Racoosin, E. B. Cluett, A. Gucwa, B. Jackson, and W. J. Brown. 2003. Inhibition of a Golgi complex lysophospholipid acyltransferase induces membrane tubule formation and retrograde trafficking. Mol. Biol. Cell. 14:3459-3469.
Brown, W. J., K. Chambers, and A. Doody. 2003. Phospholipase A2 (PLA2) enzymes in membrane trafficking: mediators of membrane shape and function. Traffic. 4:214-221.
Chambers, K., and W. J. Brown. 2004. Characterization of a novel CI-976-sensitive lysophospholipid acyltransferase that is associated with the Golgi complex. Biochem. Biophys. Res. Comm. 313: 681-868.
Chan, D., M. B. Strang, B. L. Judson, and W. J. Brown. 2004 Inhibition of membrane tubule formation and trafficking by isotetrandrine, an antagonist of G-protein regulated phospholipase A2 enzymes. Mol. Biol. Cell. 15:1871-1880.
Smirnova, E. E. B. Goldberg, K. S. Makarova, L. Lin, W. J. Brown, C. L. Jackson . 2006. ATGL has a key role in lipid droplet/adiposome degradation in mammalian cells. EMBO Rep. 7:106-113.
Listenberger, L.L., A. G. Ostermeyer-Fay, E. B. Goldberg, W. J. Brown, and D. A. Brown. 2007. Adipocyte differentiation-related protein reduces the lipid droplet association of adipose triglyceride lipase and slows triacylglycerol turnover. J. Lipid Res. 48: 2751 - 2761.
Gaspar, M. L., S. A. Jesch, R. Viswanatha, A. L. Antosh, W. J. Brown, S. D. Kohlwein, and S. A. Henry. 2008. A block in ER-to-Golgi trafficking inhibits phospholipids synthesis and induces neutral lipid accumulation. J. Biol. Chem. 283:25735-25751.
Brown, W. J., H. Plutner, D. Drecktrah, B. L. Judson, and W.E. Balch. 2008. The Lysophospholipid Acyltransferase Antagonist CI-976 Inhibits a Late Step in COPII Vesicle Budding. Traffic 8:789-797.
Schmidt, J. A., and W. J. Brown. 2009. Lysophosphatidic acid acyltransferase 3 regulates Golgi complex structure and function. J. Cell Biol. 186:211-218.