ESR6
ESR 6: Antonino Cacace
FPR2 agonists as modulators of vascular complications of diabetes
Research project
Diabetic nephropathy is characterised by non-resolved inflammation that perpetuates fibrosis resulting in eventual renal failure. This IRP develops a supporting role for the GPCR termed FPR2/ALX in protective responses evoked by LXA4 in renal fibrosis through mechanisms that include differential mRNA and miRNA expression in resident and infiltrating cells. ESR 6 will study DN to establish innovative therapeutic approaches.
S/he will generate and investigate the therapeutic potential of endogenous FPR2 agonists, both natural-derived like LXA4 derivatives and small molecules (4 prototypes from ESR10) upon exposure of mesangial cells, tubular epithelia, podocytes, macrophages and fibroblasts to prototypic mimics of DN [e.g. high glucose, TGF-b1]. The most effective of the lead molecules will be tested in vivo using an established ‘high throughput’ experimental murine model of renal fibrosis (i.e. unilateral ureteric obstruction, UUO that mimics several important features of diabetic nephropathy). Finally, the target of these agonists will be interrogated by investigating protection in a nephritic model in Fpr2 null mice (QMUL). ESR6 will also link to ESR3 and establish the effect of dihomo-γ-linoleic acid supplementation in this model, thus complementing WP1.
Main Supervisor
Name: Catherine Godson
Email: catherine.godson@ucd.ie
Host Institution
UCD Conway Institute of Biomolecular and Biomedical Research
University College Dublin
Belfield, Dublin 4
Ireland
Expected Results
The potential of FPR2/ALX agonists as lead therapeutics in DN and renal fibrosis will be established. Additionally, through collaboration with the QMUL and LMU, impacts on cardiovascular and other metabolic parameters will be investigated.
Planned secondment(s)
- QMUL, United Kingdom (September-November 2017): To apply selected compounds to the Fpr2 null mouse in models of nephropathy.
- WHRL, United Kingdom (December 2017): To train on how to design and draft preclinical contract research.
