Shruthi Krishnan

Postdoc              

Initial hypothesis and aims of the project

Based on previously published data and our preliminary data, we hypothesize that CD248 promotes diabetic kidney disease (DKD) by inhibiting the adaptive UPR response, but also by promoting maladaptive signaling. Specifically, we hypothesize that CD248 enhances ATF4 and ATF6α signaling via the UPR, inducing the maladaptive transcription factor CHOP and inflammation by modulating NF-κB signaling. Based on preliminary data and the function of UPR- and mTORC1-signalling in DKD, we also hypothesize that CD248-mediated mTORC1 pathway regulates UPR signaling, thus contributing to renal inflammation and cell death in DKD.

Aims of the project:

1. Identification of the role of CD248 in regulating the maladaptive UPR arms PERK-ATF4-CHOP and ATF6α-CHOP as well as NF-κB activation in diabetic kidney disease.
2. Characterization of the role of CD248 for mTORC1–mediated renal inflammation and the interplay between mTORC1 and maladaptive UPR signaling in diabetic kidney disease.