Division für Biochemische Pharmakologie

Pharmacological modulation of the Innate Immune response

 

Our research interests focus in understanding the human innate immune response in inflammatory diseases, in particular phagocytes activity and signaling processes involved. Based on this knowledge we intend to develop novel substances that may be specifically applied in the modulation of the immune activity (stimulation or down-regulation).

The innate immune system plays a crucial role not only in fighting infections, but also in many other diseases and medical conditions including cancer. Toll-like receptors (TLRs) are main components of this system. They recognise different molecular patterns in pathogens and also some host derived ligands resulting from tissue damage and their contribution to several inflammatory processes and in sepsis is well recognized. Thus, the discovery of substances with modulatory activity of the TLR signalling may have important implications in the therapy of a broad spectrum of pathologies (e.g. rheumatoid arthritis and cancer).

 

Group members

santos_sierra

 

Dr. Sandra Santos Sierra, Ass. Prof. (Chemist)

e-mail: sandra.santos@i-med.ac.at

phone: + 43 5129003 70451

 

Alumni

Dorothea Malecek, Bachelor Thesis (Mol. Med.)

Alexander Moser, Diploma Thesis (Physician)

Sandra Renk, Diploma Thesis (Physician)

Ramona Bruckner, Master Thesis (Biologist)

 

Collaborations (alphabetical)

Prof. S. Ebner (MUI, Innsbruck), Dr. J. Fuchs (LFU, Innsbruck), Prof. P. Henneke (CCI, Freiburg), Dr. P. Hörtnagl (MUI, Innsbruck), Prof. F Lagler (PMU, Salzburg), Prof. K. Liedl (LFU, Innsbruck), Dr. G. Wietzorrek (MUI), Prof. Wolber (FUB, Berlin)

 

Methods

Surface Plasmon Resonance, microscopy, immunoprecipitation assays, phagocytosis, ELISAs, luciferase assays, etc.

tlr

Teaching

Involved in the Molecular Medicine programs and the PhD programs “Regulation of Gene Expression” and “SPIN-Signal processing in Neurons

Recent publications:

Enhanced immunostimulatory activity of in silico discovered agonists of Toll-like receptor 2 (TLR2).
Murgueitio MS, Ebner S, Hörtnagl P, Rakers C, Bruckner R, Henneke P, Wolber G, Santos-Sierra S.
Biochim Biophys Acta. 2017 Jul 19.

Prospective virtual screening in a sparse data scenario: design of small-molecule TLR2 antagonists.
Murgueitio MS, Henneke P, Glossmann H, Santos-Sierra S*, Wolber G*
ChemMedChem. 2014

Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase.
Kenzel S, Mergen M, von Süßkind-Schwendi J, Wennekamp J, Deshmukh SD, Haeffner M, Triantafyllopoulou A, Fuchs S, Farmand S, Santos-Sierra S, Seufert J, van den Berg TK, Kuijpers TW, Henneke P.
J Immunol. 2012

Novel pharmacological chaperones that correct phenylketonuria in mice.  
Santos-Sierra S
, Kirchmair J, Perna AM, Reiss D, Kemter K, Röschinger W, Glossmann H, Gersting SW, Muntau AC, Wolber G, Lagler FB.
Hum Mol Genet. 2012

Mal connects TLR2 to PI3Kinase activation and phagocyte polarization.
Santos-Sierra S, Deshmukh SD, Kalnitski J, Küenzi P, Wymann MP, Golenbock DT, Henneke P.
EMBO J. 2009

Role of p38 and early growth response factor 1 in the macrophage response to group B streptococcus.
Kenzel S, Santos-Sierra S, Deshmukh SD, Moeller I, Ergin B, Fitzgerald KA, Lien E, Akira S, Golenbock DT, Henneke P.
Infect Immun. 2009

Lipoproteins are critical TLR2 activating toxins in group B streptococcal sepsis.
Henneke P, Dramsi S, Mancuso G, Chraibi K, Pellegrini E, Theilacker C, Hübner J, Santos-Sierra S, Teti G, Golenbock DT, Poyart C, Trieu-Cuot P.
J Immunol. 2008.

 

Funding support:

Austrian Science Fund (FWF), EKFS

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