r e s e a r c h.. p r o g r a m . o v e r v i e w

We study the roles of cellular ion transporter in cellular regulation and signaling. In particular, we focus on how certain ion transporters are regulated and on how they might play a role in cellular signaling. We use two experimental models to examine these facets of membrane ion transporters.

Our model for normal regulation is the human lung fibroblast cultured cell (MRC-5) model.  We currently use this model to examine the regulation of normal trafficking of the sodium-potassium-chloride cotransporter (NKCC) protein.  Little or nothing is known about what stimulates its synthesis, whether it is cycled into or out of the membrane and if so, what signals these transitions or what are the pathways for protein degradation.  Our lab is presently addressing all these questions Another project underway that uses this model is to determine the role of the NKCC in the normal cell cycle of this human cell line.

Our second experimental model uses the cytopathologic changes induced in the host human cell by the human cytomegalovirus (HCMV) to understand not only how a virus may co-opt ion transporter functions for its own reproduction, but also to try to gain additional insights into the role roles of these ion transporters in normal, uninfected cells. When HCMV infects cultured human fibroblasts, a distinctive cytopathology occurs prior to viral replication. HCMV cytopathology is characterized by a two-to-four-fold increase in cell size (cytomegaly). We have shown that cytomegaly is accompanied by distinctive changes in several membrane ion transporters, including the sodium pump, the Na/H exchanger, the Cl/HCO exchanger and the NKCC. We are pursuing the hypothesis that the observed changes in ion transporter activity are causally linked to cytomegaly. We further hypothesize that ion transporter changes play critical roles in viral replication. In addition, HCMV causes the host cell to partially enter the cell cycle but stop well short of cell division and it appears to block apoptosis or programmed cell death. We are pursuing the possibility that these ion transporters play critical roles in both the normal cell cycle and the HCMV effects on these transporters may be related to their roles in the normal cell cycle.

Work in our lab involves mammalian cell culture techniques, and the uses of such cell biology tools as gel electrophoresis, western blotting, metabolic labeling, biotinylation labeling, immunostaining, immunoprecipitation, confocal microscopy, and cell sorting/counting.

Undergraduate students: Please click here for information about research opportunities in my lab.