Genetic Analysis of Signal Transduction with Reference to Type 2 Diabetes

We have automated a method to accelerate the identification of the intracellular paths that underlie cellular communication and pathogenic responses in the immune system. As part of that program we have created robotic approaches that allow the rapid identification of genes that control transcriptional activation, subcellular localization and receptor deactivation. We have also developed systems for rapid generation of mice bearing targeted disruptions of specific candidate genes. We are integrating the two approaches with an emphasis on signaling pathways that influence organismic responses to metabolic load and pathogens.

Several of the pathways that have been studied have been found connected with general mechanisms for maintaining energy homeostasis. A particularly prominent theme has been the interactions of genes that control immune responses and those that mediate the balance of catabolism and anabolism. An improved understanding of the factors that regulate inflammation and its influences on energy utilization may deepen our understanding of the traits that increase the risk for diabetes and the possible consequences of interventions directed against one or more of the gene products identified here.


1. Zhou G.L., Beloiartsev A., Yu B., Baron D.M., Zhou W., Niedra R., Lu N., Tainsh L.T., Zapol W.M., Seed B., Bloch K.D. Deletion of the murine cytochrome P450 Cyp2j locus by fused BAC-mediated recombination identifies a role for Cyp2j in the pulmonary vascular response to hypoxia. PLoS Genet. 9:e1003950. PMC3836722 (2013)

2. Freeman J., Kriston-Vizi J., Seed B., Ketteler R. A high-content imaging workflow to study Grb2 signaling complexes by expression cloning. J Vis Exp. PMC3499067 (2012)

Cho J.L., Roche M.I., Sandall B., Brass A.L., Seed B., Xavier R.J., Medoff B.D. Enhanced Tim3 activity improves survival after influenza infection. J Immunol. 189:2879-89. PMC3436990 (2012)

3. Wang X., Spandidos A., Wang H., Seed B. PrimerBank: a PCR primer database for quantitative gene expression analysis, 2012 update. Nucleic Acids Res. 40:D1144-9. PMC3245149 (2012)

4. Lindquist S., Karitkina D., Langnaese K., Posevitz-Fejfar A., Schraven B., Xavier R., Seed B., Lindquist J.A. Phosphoprotein associated with glycosphingolipid-enriched microdomains differentially modulates SRC kinase activity in brain maturation. PLoS One. 6:e23978. PMC3167820 (2011)

5. Kim H., Seed B. The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3. Nat Immunol. 11:743-50. PMC3050627 (2010)

6. Westerberg L.S., Meelu P., Baptista M., Eston M.A., Adamovich D.A., Cotta-de-Almeida V., Seed B., Rosen M.K., Vandenberghe P., Thrasher A.J., Klein C., Alt F.W., Snapper S.B. Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes. J Exp Med. 207:1145-52. PMC2882832 (2010)

7. Ketteler R., Tomov V., Neunkirchner A., Xie Q., Pickl W.F., Seed B. Host-encoded reporters for the detection and purification of multiple enveloped viruses. J Virol Methods. 167:178-85. PMC2916077 (2010)

8. Kueng H.J., Manta C., Haiderer D., Leb V.M., Schmetterer K.G., Neunkirchner A., Byrne R.A., Scheinecker C., Steinberger P., Seed B., Pickl W.F. Fluorosomes: a convenient new reagent to detect and block multivalent and complex receptor-ligand interactions. FASEB J. 24:1572-82. PMC2879947 (2010)

9. Spandidos A., Wang X., Wang H., Seed B. PrimerBank: a resource of human and mouse PCR primer pairs for gene expression detection and quantification. Nucleic Acids Res. 38:D792-9. PMC2808898 (2010)