Professor of Physiology
Institute for Physiology
Center for Physiology and Pharmacology
Schwarzspanierstrasse 17, 1090 Vienna, Austria
Phone: +43 (0)1 40160 - 31427
FAX: +43 (0)1 40160 - 931101
Macrophages and dendritic cells, innate immunity, PI3K/PTEN and related signal transduction, autoimmunity, tumor immune surveillance.
Signaling pathways modulating macrophage- and dendritic cell-function in infectious as well as non-infectious inflammatory diseases
The main focus of my lab is concentrated on the elucidation of immune-modulating signaling pathways and their involvement in pathophysiologic processes in innate immune cells such as macrophages and dendritic cells.
In particular we are interested in the role of the PI3-Kinase pathway and its antagonistic lipid phosphatase PTEN in the modulation of infectious and non-infectious inflammatory processes.
We could show that PI3K downregulates inflammation and coagulation in acute inflammatory processes 4.
Genetic analysis revealed an important immune-modulatory role not only for PI3K but also for PTEN in LPS mediated TLR4 signaling in macrophages 2.
Recently we could extend our findings to models including clinically relevant pathogens, showing that PTEN deficiency specifically in myeloid cells dampens the innate immune response to bacterial infections of the lung 1,3.
On a related topic we could publish a paper showing that ablation of the PTEN gene promotes osteoclastogenesis as well as bone destruction in a murine model of TNFa-induced inflammatory arthritis 5.
Taken together we postulate that the PI3K/PTEN pathway essentially contributes to the regulation of inflammatory processes in innate immune cells.
Currently we are investigating effects of cell-type specific PTEN deficiency in murine models of non-infectious acute and chronic inflammation and different models of autoimmunity.
For instance we could find that antigen presentation was dramatically altered in PTEN deficient mice resulting in differential T-cell polarization in collagen induced arthritis. We aim to elucidate the molecular mechanisms relevant for this interesting phenomenon.
Furthermore we found alternative activation of macrophage depending on PTEN expression. We assume that this type of activation of macrophage will alter the course of chronic inflammation and inflammation induced colon cancer. This will be done in murine models of fibrosis and colitis.
S.Blüml, “Loss of phosphatase and tensin homolog (PTEN) in myeloid cells controls inflammatory bone destruction by regulating the osteoclastogenic potential of myeloid cells,” Ann Rheum Dis. 2013 Dec 10.
G. Schabbauer, "Myeloid PTEN promotes inflammation but impairs bactericidal activities during murine pneumococcal pneumonia," J. Immunol. 185(1), 468 (2010).
P. Gunzl, "Anti-inflammatory properties of the PI3K pathway are mediated by IL-10/DUSP regulation," J. Leukoc. Biol. 88(6), 1259 (2010).