Paul N. BlackChair, Professor Lab Webpage |
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Research Interests:
Fatty acid transport proteins, fatty acid trafficking, metabolic transformation.
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:
[1] 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.
[2] 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.
[3] 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.
[4] Establishing a state-of-the-art lipidomic core to facilitate studies on fatty acid trafficking including complex lipid turnover using stable isotopes.
