Ron Yahil

Present Position: Graduate Student

Previous Position: Research Technician at the Wistar Institute (2001-04) (Ellen Pure's lab)

Undergraduate: Reed College, B.A. (2000) Biochemistry and Molecular Biology

Research interests: Immune complex driven IL-10 production by macrophages and DC

Publications:

Kothapalli, D., Fuki, I., Ali, K., Stewar, S.A., Zhao, L., Yahil, R., Kwiathowski, D., Hawthorne, E.A., FitzGerald, G.A., Phillips, M.C., Lund-Katz, S., Pure, E., Rader, D.J., Assoian, R.K.  2004.  Antimitogenic effects of HDL and APOE mediated by Cox-2-dependent IP activation. J. Clinical Investigation 113(4):609-18.

Research Summary:

Current research in the Mosser lab is focused on the genetic regulation of IL-10.  We have already shown that cross-linking of the FCgR of macrophages with immune complexes, combined with simultaneous stimulation by Toll-like receptor ligands (e.g. LPS), causes a robust secretion of IL-10 as well as a marked decrease in IL-12 production.  These concurrent signals result in activation of ERK which then leads to chromatin remodelling of the IL-10 locus, specifically phosphorylation of histone H3 followed by a less robust acetylation.  Since these events are not observed elsewhere in the IL-10 promoter region, nor have they been described in other gene promoter regions, we believe that they represent a unique method of cytokine gene regulation.

Recently searches of EST databases has led to the discovery of an entire family of Class 2 cytokine that share structural and/or sequence homology to IL-10.  These include IL-19, IL-20, IL-22, IL-24 (Mda-7), IL-26, interferons (IFN-a,-b, -e, -k, -w, -d, -t, and -g) and interferon-like molecules (limitin, IL-28A, IL28B, and IL-29).  I want to determine whether the regulator events observed with IL-10 are in fact unique to this gene, or instead are a common theme of this family of cytokines.  Since IL-19 is expressed by macrophages and lies upstream of the IL-10 gene on the same chromosome, it seemed a likely candidate to address this question.  Indeed, initial studies have shown that IL-19 gene transcription is upregulated by stimulation with LPS and immune complexes, as compared to stimulation with LPS alone.  I hope to further characterize the kinetics of IL-19 gene transcription as well as the relevant signalling molecules and chromatin remodelling events necessary for transcription of this gene.