Prof. Dr. med. Paul Thomas Brinkkötter
Department II of Internal Medicine
University Hospital Cologne
Kerpener Str. 62
50937 Cologne, Germany
+49 221 478-30627
paul.brinkkoetter@uk-koeln.de

Address of the institution:

University Hospital of Cologne
Center for Molecular Medicine Cologne (CMMC)
Robert-Koch-Str. 21
50937 Cologne

Research project 6

Targeting metabolic pathways in focal segmental glomerulosclerosis

Paul Brinkkötter

Recent fundamental studies highlighted the pivotal role of insulin signaling in podocytes beyond mere glucose uptake comprising activation of AKT and mTOR. We have shown that insulin signaling in podocytes is tightly controlled by mitochondrial function. An impairment of the mitochondrial fusion and fission machinery is associated with an increased activation of the insulin signal cascade. Yet, it remains elusive whether the activation of the insulin cascade in podocytes is the result of canonical insulin receptor and IGF-1 signaling, or whether it follows insulin-independent intrinsic pathways. Here, our overarching goal is to gain mechanistic insights into the role of deregulated insulin signaling in the pathogenesis of FSGS and to understand the specific contributions of nutrient sensing mTOR signaling and FoxO transcriptions factor activity. For this purpose, we will delineate the contribution of mitochondria to these signaling networks in FSGS and perform extensive proteomic and phospho-proteomic analyses using primary podocytes as well as cell lines. In an independent approach, we will systematically characterize the activities of insulin signaling networks during the development of focal and segmental glomerulosclerosis (FSGS) using several independent models of podocyte injury in a very high temporal resolution.