Honorary departmental postdoctoral research assistant
Investigating the interaction of chemokines with the extracellular matrix
Chemokines are small secreted proteins, whose best studied function is the recruitment of target cells between tissues and the positioning of cells therein, although evidence suggests additional tasks in immunology, for instance regulating cell survival or differentiation. The pivotal roles of chemokines in cancer, e.g. as guidance cues for trafficking of leukocytes into the tumor microenvironment or as inducers of tumor cell proliferation, suggest a big translational potential of this target class. However, thus far chemokine targeting was not crowned with success.
A very important and often overlooked aspect is, that chemokines do not act alone. While chemokine presentation on the endothelium via proteoglycans has been well studied, one area about which we know very little is chemokine presentation/immobilization in the tumor microenvironment via the extracellular matrix (ECM). The interaction of chemokines with ECM components could be a missing link explaining the multitude of chemokine’s different effects and also the challenges of therapeutically targeting them.
The aim of my project is to investigate the interaction of chemokines with the ECM in the context of the tumor microenvironment from a molecular/biochemical and an immunological/cellular point of view.
Glycosaminoglycans are important mediators of neutrophilic inflammation in vivo.
Gschwandtner M. et al, (2017), Cytokine, 91, 65 - 73
Interfering with the CCL2-glycosaminoglycan axis as a potential approach to modulate neuroinflammation.
Gschwandtner M. et al, (2016), Neuroscience letters, 626, 164 - 173
Preparation and Characterization of Glycosaminoglycan Chemokine Coreceptors.
Kitic N. et al, (2016), Methods in enzymology, 570, 517 - 538
Glycosaminoglycan silencing by engineered CXCL12 variants.
Gschwandtner M. et al, (2015), FEBS letters, 589, 2819 - 2824
A combinatorial approach to biophysically characterise chemokine-glycan binding affinities for drug development.
Gerlza T. et al, (2014), Molecules (Basel, Switzerland), 19, 10618 - 10634