FATTT Lab: Fatty Acid Transport, Trafficking and Transcriptional Regulation

Telephone: (518) 641-6461
Fax: (518) 641-6304
pblack@ordwayresearch.org

Research Focus

Dr. Black's research is directed to determine the components and mechanisms governing fatty acid transport across biological membranes and how these events are liked to downstream fatty acid trafficking and metabolism. Of particular interest are the multiple isoforms of the fatty acid transport proteins and the fatty acyl CoA synthetases.

Abnormalities in lipid metabolism are major contributing factors to various disease states including obesity, diabetes, and cardiomyopathies. Together, these diseases are the leading cause of death in the United States and most other developed countries. It is hypothesized that high circulating levels of lipids lead to internalization and the resultant lipotoxicity of normal cells and tissues. Prevention of these disease states and therapeutic intervention therefore is desired and requires an understanding of the underlying molecular mechanisms leading to import and trafficking of fatty acids. Current efforts are directed towards defining the roles of the fatty acid transport proteins (FATP) and the fatty acyl CoA synthetases (ACSL) in fatty acid transport and trafficking. This includes:

• Defining how these proteins promote both selectivity and specificity of different classes of fatty acid (saturated, monounsaturated and polyunsaturated) and assessing whether they function individually or in concert with each other. This work addresses how these proteins influence fatty acid homeostasis and more specifically their discrete roles in fatty acid trafficking.
• Defining the domain organization of selected members of the FATP and ACSL family, including mechanistic enzymology and structure/function studies. These studies include the production of protein chimeras and directed mutagenesis to define the roles of different domains within these proteins.
• Defining the three-dimensional structures of selected members of the FATP and ACSL family. This work includes protein expression using mammalian, yeast and bacterial expression systems, protein purification and through collaborative efforts crystallography trials.
• Establishing a state-of-the-art lipidomic core to facilitate studies on fatty acid trafficking using stable isotopes.

Selected Publications
www.pubmed.com

• Zou, Z., DiRusso, C. C., Ctrnacta, V. and Black, P. N. 2002. Fatty Acid Transport in Saccharomyces cerevisiae. Directed mutagenesis of FAT1 distinguishes intrinsic activities associated with Fat1p. The Journal of Biological Chemistry, 277: 31062-31071.


• Zou, Z., Tong, F., Færgeman, N. J., Børsting, C., Black, P. N., and DiRusso, C. C. 2003. Vectorial acylation in Saccharomyces cerevisiae: Fat1p and fatty acyl-CoA synthetase are interacting components of a fatty acid import complex. The Journal of Biological Chemistry, 278: 16414-1642.
  
• Berg, B. V., Black, P. N., Clemons, W. M., and Rapoport, T. A. 2004. Crystal structure of the long-chain fatty acid transporter FadL. Science, 304: 1506-1509.
  
• Mashek, D. G., Bornfeldt, K. E., Coleman, R. A., Berger, J., Bernlohr, D. A., Black, P., DiRusso, C. C., Farber, S. A., Guo, W., Hashimoto, N., Khodiyar, V., Kuypers, F. A., Maltais, L. J., Nebert, D. W., Singh, I., Schaffer, J. E., Stahl, A., Watkins, P. A., Vasiliou, V., and Yamamoto, T. T., 2004. Revised nomenclature for the mammalian acyl-CoA synthetase gene family. Journal of Lipid Research, 45: 1958-1961.
  
• DiRusso, C. C., Li, H., Darwis, D., Berger, J., Watkins, P. A. and Black, P. N. 2005. Comparative biochemical studies of the murine fatty acid transport proteins expressed in yeast. The Journal of Biological Chemistry, 280: 16829-16837.
  
• Black, P. N., Li, H., Tong, F. and DiRusso, C. C. 2005. The gateway to fat in yeast: The cell biology fatty acids. In: Cell Biology and Dynamics of Yeast Lipids, (Guenther Daum, ed.), 1-20.
  
• DiRusso, C. C. and Black, P. N. 2006. Acyl-CoA synthetases at the crossroads between lipid metabolism and regulation. Biochimica et Biophysica Acta (Lipids), In Press.

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