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Research Interests


 
In our laboratory we study intracellular signaling mechanisms in lymphocytes during the immune response to foreign and self (autoimmunity) antigens.

Our current focus is on Complement proteins and their specific receptors on lymphocytes that “bridge” innate and adaptive immune responses, providing an important functional link between these two phylogenetically distant defense systems. Complement and antibodies play important roles in the development of autoimmunity. In particular, Complement receptor 2 (CR2) has been demonstrated to be essential in the development of autoimmune diseases such as arthritis and myocarditis. Our long term goal is to characterize signal transduction mechanisms underlying complement-mediated B cell activation that are important in autoimmune disorders where complement and antibodies play a key role in pathogenesis. C3dg is a cleavage product of the C3 component of complement that can through its interactions with CR2 greatly amplify signals transmitted through the binding of C3dg-attached antigen with its specific B cell antigen receptor (BCR). Our data indicate that there are important qualitative differences between the mechanisms of complement-dependent and -independent B cell activation. Better understanding of this novel mechanism provides an opportunity for a potential new therapeutic approach whereby activation of self-reactive B cells can be down-modulated in a beneficial manner.

Our research relies heavily on fluorescent digital imaging techniques such as:

• Microscopy
-real-time intracellular Ca2+ imaging
-fluorescence-based receptor/ligand trafficking on planar supported lipid bilayers
-Fluorescent Resonance Energy Transfer (FRET) imaging
-digital 3D reconstruction, particle tracking and volume rendering
-immunofluorescent imaging of intracellular signal transduction molecules and cell surface receptors in fixed cells and tissue sections
-2-photon fluorescent microscopy in live tissue

• Flow cytometry
-combination of intracellular phospho-protein fluorescent labeling and surface markers for differential analysis of activation in lymphocyte populations
-real-time Ca2+ influx analysis in lymphocyte populations responding to a stimulus

Other methods used in our laboratory are:

• Western blotting, 2D analytical electrophoresis
• DNA cloning, plasmid engineering, PCR, DNA sequencing/genomics
• recombinant protein production and purification in pro-and eucaroityc systems
• surgery in laboratory animals


Examples of imaging data generated in our laboratory