Retinoic Acid Homeostasis

One of the main areas of interest in our lab is vitamin A and retinoic acid homeostasis with special focus on the processes that mediate the synthesis of retinoic acid from vitamin A and the elimination of retinoic acid from target cells and from the body. We research the biochemistry and clinical significance of the enzymes in the Cytochrome P450 family 26. These include CYP26A1, CYP26B1 and CYP26C1 that are responsible for the clearance of retinoic acid from the body. Our research projects include basic studies on how these enzymes function, their structure-function and their specific expression patterns in human and animal tissues. We also investigate how these enzymes maintain specific tissue health and how alterations in their activity and expression may play a role in disease progression or toxic effects of environmental factors or xenobiotics. As more discoveries are made in the genetics of these enzymes we are actively involved in projects that aim to characterize how genetic variability in CYP26 activity may affect risks of disease development. In the area of retinoic acid synthesis we work on characterizing the alcohol and aldehyde dehydrogenase enzymes that are responsible for formation of retinoic acid in various tissues with special focus on their expression and activity in the testes, kidney, liver, lung and the pancereas.

RA-homeostasis

Overall schematic of retinoic acid homeostasis

CYP26A1 homology model

Homology model of CYP26A1 with retinoic acid in the active site. Figure adapted from Shimshoni et al 2012 by Art Roberts

International Innovation report article

Click on image to read story of CYP26 enzymes and our research