This application is for Dr. Jennie Lin to develop her career as an academic physician-scientist focusing on the functional genomics of chronic kidney disease (CKD). The proposed studies and mentored activities will take place at Northwestern University's Feinberg School of Medicine, which offers a remarkably rich research environment that will foster the candidate's professional development. The proposed research focuses on elucidating the molecular basis of the macrophage’s role in APOL1-mediated kidney disease with single-cell resolution. Human genetics studies have identified two common coding variants, G1 and G2, in the APOL1 gene encoding apolipoprotein L1 (APOL1) that drive the disproportionately increased risk of CKD and end-stage renal disease (ESRD) in African Americans. Despite the large effect these variants have on kidney disease, not all individuals with the high-risk APOL1 genotype, i.e., carrying two risk alleles, develop CKD. We currently lack an understanding of which patients will develop APOL1-mediated kidney disease, and we currently do not have therapeutic strategies to mitigate disease risk. This proposal aims to investigate using single-cell transcriptomics (1) how APOL1 risk variants influence macrophage-kidney crosstalk and the intracellular stress response of different cell types in 3D kidney cell culture models and (2) how APOL1 risk variants modulate inflammatory profiles and responses of induced pluripotent stem cell (iPSC) derived macrophages. Completion of the proposed studies will generate crucial data for understanding the molecular underpinnings of APOL1-mediated kidney disease and prepare the candidate to compete successfully for R01 funding in the near future.
|Effective start/end date||7/1/19 → 6/30/21|
- National Kidney Foundation of Illinois (Award Email 6/28/19)