Dynamic signalling networks in Diabetic Nephropathy (DN) – New avenues to a personalized therapy.-
We have developed an exquisite experimental platform that facilitates the systematic unravelling of the signalling
networks leading to (1) the initiation, (2) the progression and (3) the potential regeneration of podocytes in
DN, paving the way to novel therapeutic strategies:
(1) DN initiation: Identification of signalling cascades leading to microalbuminuria: Molecular
By combining transgenic Drosophila lines carrying secreted fluorescent proteins to monitor the barrier function
in vivo with a genome-wide siRNA screen we will establish a unique system to directly identify gene
networks contributing to microalbuminuria.
(2a) DN progression: Molecular fingerprinting of podocyte degeneration: Based on a transgenic
fluorescent mouse model, we have pioneered a highly efficient podocyte purification method from type1 and
type 2 diabetic mice allowing us to develop a precise molecular genetic, quantitative proteomic and micro
RNA fingerprint from freshly isolated podocytes from diabetic and non-diabetic mice.
(2b) DN progression: We established a proteomic approach to measure site-specific phosphorylation dynamics in
primary podocyte cultures originating from transgenic mice that are TORC1 deficient, TORC2 deficient or
TORC1 hyperactive (TSC1 KO) solely in the podocytes.
(3) Potential role of podocyte regeneration in DN: Finally, to target mechanisms that could potentially
reverse the disease process (by repopulating lost podocytes), we invented a strategy to quantitatively monitor
podocyte turnover from different stem cell niches allowing us to precisely assess and potentially
manipulating the capacity of podocyte regeneration in DN.