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The Moise Lab

Lab Members

• Linsee Addington – Student Research Assistant
• Ben Jang – Student Research Assistant
• Sara Billings – Research Assistant
• Xiaoyan Pang, Ph.D. – Post-Doctoral Research Associate

Research Interestes

My research centers on the metabolism of vitamin A, or retinol, which plays essential roles in the processes of vision, development, cellular differentiation and immunity in vertebrates. The two known bioactive vitamin A metabolites are retinoic acid, which activates the retinoic acid receptor (RAR), and 11-cis-retinal, the visual chromophore. Our studies examine the regulation of retinoid metabolism and the physiological roles of classical and novel retinoid metabolites.

Research Projects

Our research projects address the following topics:

We described an alternate pathway in the metabolism of vitamin A that is initiated by the enzyme retinol saturase (RetSat), which saturates all-trans-retinol to produce (R)-all-trans-13,14-dihydroretinol (1,2). RetSat displays sequence homology and has similar enzymatic mechanism as carotene synthesizing enzymes from plants (3). (R)-all-trans-13,14-dihydroretinol undergoes oxidation leading to the formation of (R)-all-trans-13,14-dihydroretinoic acid, a potential ligand of RAR (4,5). We characterized the role of RetSat using genetic animal models (6) and we analyzed the biological activity of dihydroretinoid metabolites using pharmacological screens (7). Our results suggest that RetSat diverts retinoid metabolism from the production of retinoic acid to produce novel bioactive retinoids that might play roles in lipid metabolism and/or the regulation of energy balance.

Regulation of retinoid transport and metabolism
We are interested in the processes that govern the production of bioactive retinoids. Previously, we described the membrane topology of the enzyme lecithin: retinol acyltransferase, one of the key factors regulating vitamin A uptake and storage (8). In our current studies, we pursue the structural characterization of proteins and enzymes involved in retinoid metabolism and the identification of the transcriptional and post-translational regulatory mechanisms that govern their level and activity. These studies could improve our understanding of the delivery of retinoids and retinoid-based drugs (9) and could provide a framework for the development of pharmacological modulators of retinoid enzymes with possible therapeutic applications.

For more information about our lab, research projects and positions available please visit www.midwestlipids.com

Postdoctoral Position Available

A postdoctoral position is available in the Department of Pharmacology and Toxicology in the School of Pharmacy at the University of Kansas to study nuclear receptor signaling pathways and retinoid metabolism. Experience in biochemistry, molecular biology, structural biology, mass spectrometry or chemistry required. Please contact Dr. Alex Moise (alexmoise@ku.edu) for more information.

References

1. Moise, A.R., Kuksa, V., Imanishi, Y., and Palczewski, K. (2004) J. Biol. Chem. 279, 50230-50242 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2665716
2. Moise, A.R., Isken, A., Dominguez, M., de Lera, A.R., von Lintig, J., and Palczewski, K. (2007) Biochemistry 46, 1811-1820 http://www.pubmedcentral.gov/articlerender.fcgi?tool=nihms&artid=2561287
3. Moise, A. R., von Lintig, J., and Palczewski, K. (2005) Trends Plant Sci. 10, 178-186 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=nihms&artid=1351244
4. Moise, A.R., Kuksa, V., Blaner, W.S., Baehr, W., and Palczewski, K. (2005) J. Biol. Chem. 280, 27815-27825 http://www.pubmedcentral.gov/articlerender.fcgi?tool=nihms&artid=1352314
5. Moise, A.R., Dominguez, M., Alvarez, S., Alvarez, R., Schupp, M., Cristancho, A.G., Kiser, P.D., de Lera, A. R., Lazar, M.A., and Palczewski, K. (2008) J. Am. Chem. Soc. 130, 1154-1155
6. Moise A.R., Lobo G.P., Erokwu B., Wilson D.L., Peck D., Alvarez S., Domínguez M., Alvarez R., Flask C.A., de Lera A.R., von Lintig J., Palczewski K. FASEB J. (in press)
7. Moise A.R., Alvarez S., Dominguez M., Alvarez R., Golczak M., Lobo G.P., von Lintig J., de Lera A.R., Palczewski K. Mol. Pharmacol. Sep 21, 2009 (epub)
8. Moise, A.R., Golczak, M., Imanishi, Y., and Palczewski, K. (2007) J. Biol. Chem. 282, 2081-2090
9. Moise, A.R., Noy, N., Palczewski, K., and Blaner, W.S. (2007) Biochemistry 46, 4449-4458 http://www.pubmedcentral.gov/articlerender.fcgi?tool=nihms&artid=2562735