Signal transduction in health and disease: the role of cAMP signalling pathways.
The group's work addresses major health problems such as cancer, cardiovascular disease and obesity, as well as AIDS and other infectious diseases. Currently, the group is focused on understanding intracellular signalling pathways and in particular, how cAMP signalling networks cross-talk with and integrate into the complex web of signalling pathways. In order to perform their research, the group also establishes new tools and technology platforms for in-depth study of these pathways and to promote the development of highly specific pharmaceuticals with minimal side-effects. Furthermore, several translational research projects are running, including the discovery of and intervention with mechanisms of suppression of anti-tumor immunity, development of immunostimulating therapies in HIV and perturbation of damaging signal pathways in heart failure.
- To understand how signalling networks mediate hormonally regulated physiological and pathophysiological processes (e.g. PGE2-stimulation)
- To investigate the role of anchoring proteins in signalling networks and to engineer specific anchoring disruptors to perturb signalling in defined localizations
- To understand the role of the cAMP second messenger system in the regulation of T cell function and immunomodulation, and the significance in immune diseases and inflammation
- To better characterise regulatory T cell subsets and investigate their intercellular communication and functions
- To develop mouse transgenic models and disease models for testing of small-molecule disrupters in 'Proof-of -Principle' experiments
The Taskén group has several projects currently running. More information about these projects is found here.
- We have developed a solid competence and broad basis of knowledge in the area of human cAMP/PKA.
- We have identified and characterised of a number of AKAPs involved in regulating different physiological processes.
- We have contributed significantly to the understanding of the molecular mechanisms of cAMP modulation of T cell immune function with clinical relevance in immunodeficiencies and cancer.
- We have established a number of techniques for the analysis of protein-protein interactions and complex signalling patterns (e.g. phospho-flow cytometry, peptide array and Chemical Biology HTS)
- In the past ten years, we have published well over 100 original research articles as well as a number of reviews and book chapters.
A variety of techniques are available for screening new targets for in vitro and in vivo function, including high-throughput screening assays and genetic tools:
- High-throughput screening assays
- Reporter assays
- Biochemical activity assays
- Biochemical purification of lipid rafts
- Expertise in purification of primary cells (T cells, B cells, NK cells) and analysis of lymphocyte effector functions (proliferation, cytokine production, cytotoxicity) is available.
- RNA interference
- Peptide array
- Chemical proteomics
- Phospho-flow analysis
Ten publications from the last five years are listed below:
- Pidoux G, Witczak O, Jarnæss E, Myrvold L, Urlaub H, Stokka AJ, Küntziger T, Taskén K. (2011) Optic atrophy 1 is an A-kinase anchoring protein on lipid droplets that mediates adrenergic control of lipolysis. EMBO J. (Epub ahead of print)
- Kalland ME, Oberprieler NG, Vang T, Taskén K, Torgersen KM (2011) T Cell-Signaling Network Analysis Reveals Distinct Differences between CD28 and CD2 Costimulation Responses in Various Subsets and in the MAPK Pathway between Resting and Activated Regulatory T Cells. J. Immunol. (Epub ahead of print)
- Solstad T, Bains SJ, Landskron J, Aandahl EM, Thiede B, Taskén K, Torgersen KM (2011) CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells. Blood (Epub ahead of print)
- Mosenden, R., Singh P., Cornez, I., Heglind, M., Ruppelt, A., Moutschen, M., Enerbäck, S., Rahmouni, S., Taskén K. (2011) Mice with disrupted type I protein kinase A anchoring in T cells resist retrovirus-induced immunodeficiency. J. Immunol. 186:5119-30.
- Oberprieler, N.*, Lemeer, S.*, Kalland, M.E., Torgersen, K., Heck, A.J.R., Taskén, K. (2010) High-resolution mapping of prostaglandin E2-dependent signaling networks identifies a constitutively active PKA signaling node in CD8+CD45RO+ T cells. Blood, 116:2253-65. (*First authors)
- Bjørgo, E., Solheim, S.A., Abrahamsen, H., Baillie, G.S., Brown, K.M., Berge, T., Okkenhaug, K., Houslay, M.D., Taskén, K.. (2010) Cross talk between phosphatidylinositol 3-kinase and cyclic AMP (cAMP)-protein kinase a signaling pathways at the level of a protein kinase B/beta-arrestin/cAMP phosphodiesterase 4 complex. Mol. Cell. Biol., 30: 1660-72.
- Jarnæss, E., Ruppelt, A., Stokka, A.J., Lygren, B., Scott, J.D., Taskén, K. (2008) Dual specificity A-kinase anchoring proteins (AKAPs) contain an additional binding region that enhances targeting of protein kinase A type I. J. Biol. Chem., 283: 33708-33718.
- Mahic, M., Yaqub, S., Bryn, T., Henjum, Eide, D.M., Torgersen, K.M., Aandahl, E.M., Taskén, K. (2008) Differentiation of naive CD4+ T cells into CD4+CD25+FOXP3+ regulatory T cells by continuous antigen stimulation. J. Leukocyte Biol., 83:1111-7.
- Lygren, B.*, Carlson, C.R.*, Santamaria, K., Lissandron, V., McSorley, T., Rosenthal, W., Zaccolo, M., Taskén, K.#, Klussmann, E. (2007) AKAP-complex regulates Ca2+ reuptake into heart sarcoplasmic reticulum. EMBO Reports, 8:1061–1067
- Ruppelt, A., Mosenden, R., Grönholm, M., Aandahl, E.M., Tobin, D., Carlson, C.R., Abrahamsen, H., Herberg, F.W., Carpén, O. Taskén, K. (2007) Inhibition of T cell activation by cAMP requires lipid raft targeting of protein kinase A type I by the A-kinase anchoring protein Ezrin. J. Immunol., 179:5159-68.