- Mast Cell Signaling
Our research interests are in calcium signaling mechanisms via lipid second messengers in mast cells. Stimulation of mast cells via the high affinity receptor for IgE (Fc?RI) leads to the release of inflammatory mediators that are responsible for allergic inflammatory diseases, such as asthma and allergic dermatitis. The release of inflammatory mediators is dependent on the increase in cytosolic free Ca2+ ([Ca2+]i), which is initiated by the mobilization of Ca2+ from the endoplasmic reticulum (ER) and followed by influx of Ca2+ from outside of the cell. It is generally believed that inositol 1,4,5-trisphosphate (IP3) is responsible for mobilizing Ca2+ from the intracellular stores. We previously demonstrated that Fc?RI-mediated production of IP3 is not sufficient to account for the increase in [Ca2+]i and suggested an alternative mechanism for Ca2+ mobilization via sphingosine 1-phosphate, a product of sphingosine kinase. In an effort to identify the enzyme responsible for the production of sphingosine 1-phosphate in the endoplasmic reticulum, we discovered that overexpression of the ? isoform of Class II phosphoinositide 3-kinase (PI3KC2?) in a mast cell line (RBL-2H3) cells caused an increase in sphingosine 1-phosphate production and Ca2+ mobilization. It is not clear at present how PI3KC2? causes sphingosine 1-phosphate production. It may have intrinsic sphingosine kinase activity or may recruit a sphingosine kinase such as SPHK1 to produce sphingosine 1-phosphate in the ER. Currently, we are investigating the signaling pathway that leads to the activation of PI3KC2? and SPHK1 upon stimulation of Fc?RI and downstream signals of these enzymes.
Oksoon H. Choi, Ph.D.
Assistant Professor- senior laboratory investigator
Huyn-Sil Lee, Ph.D.
Postdoctoral Fellow, currently studying the role of sphingosine kinase in calcium signaling and release of sphingosine 1-phosphate from mast cells.
Ho Young Suk, Ph.D.
Postdoctoral Fellow, currently trying to identify upstream signaling molecules of PI3KC2? using siRNA knockdown and site-directed mutagenesis approaches.
Positions are available for qualified and motivated post-doctoral fellows. Please inquire via email to firstname.lastname@example.org
Last Updated: 3/31/06