Summary outlining the primary research activity

Cellular signaling

     The research in my laboratory involves deciphering complex signaling systems and control networks using immune cells. We have analyzed transcriptional and cytokine changes after the addition of a single (2MA, Anti-Ig, BAFF, BLC, Bombesin, C5a, CD40L, CGS, CpG, CSF, Dimaprit, ELC, fMLP, GMF, IFNa, IFNb, IFNg, IGF1, IL1b, IL4, IL6, IL10, ISO, KDO, LPA, LPS, LTB4, MIP3a, Neurokinin B, Neuropeptide Y, NGF, PAF, PAM2, PAM3, PGE2, PolyIC, R-848, S1P, SDF1, SLC, Taxol, TER, TGFb, TNFa, UDP, UTP, Zymosan, etc) or multiple ligands (2MA, 8BR, IFNb, IFNg, IL6, ISO, KDO, LPS, PGE2, TGFb, etc) in mouse B cells and macrophages. A time series examining the combinational effects of endogenous or exogenous ligands enabled identification of the signal networks causing crosstalk effects related to Toll-like receptors (TLR), G protein coupled receptors (GPCR), and others. We have also examined the effectiveness of RNA interference (RNAi) methodology using macrophage cells transfected with lentiviral small hairpin RNA (shRNA), small interfering RNA (siRNA) or antisense oligonucleotide in order to further develop RNAi as a gene knockdown tool.

     Biological processes are driven by complex systems of functionally interacting macromolecules. Systems biology combined with molecular biological tools is ideal for the identification of the genes involved in these processes and the description of the signaling pathways that regulate them. Complex biological phenomena can be understood in terms of the interactions of functioning components, and network perturbations and the measurement of cellular responses can be used to probe connectivity and signaling system function.