My group focuses on epigenetic regulation in kidney disease. The aim is to understand the transcriptional regulation of kidney specific programs in normal homeostasis and in kidney injury and repair with focus on enhancer hierarchies, transcription factor identification / cooperation and in-vivo validation with CRISPR/Cas9 gene or base editing tools. We believe our comprehensive analysis of epigenetic changes after kidney injury in-vivo provides a detailed molecular model and rich resource, and has the potential to identify new targets for therapeutic intervention.
Background and Significance
Chronic kidney disease (CKD) is common, affecting 1 in 7 people in first‐world countries, and is associated with high morbidity, mortality and socioeconomic burden. CKD brings vast costs to healthcare systems and dialysis alone has an estimated cost of 14 billion euros per year in the EU. The evelopment of progressive CKD is frequently caused by repeated and severe injury to the kidney as a result of diabetes, hypertension, nephrotoxic substances or AKI. Regardless of the initial insult, progression to CKD is characterized by nephron loss including tubular atrophy, interstitial fibrosis and glomerulosclerosis. The patho‐biological mechanisms of progressive CKD are incompletely understood. Recent findings highlight the consequences of the injury and repair process (e.g. after AKI) to the development and progression of CKD, especially if it is incomplete and a ‘maladaptive’ repair.
On the cellular level, previous studies have identified surviving tubular epithelial cells as the main cellular source of the repair process in the kidney through robust proliferation of the tubular epithelium. The proliferating tubular epithelial cells rapidly activate transcriptional injury and repair programs.
We are particularly interested in these molecular changes after kidney injury as their prolonged expression associated with severe and repeated injury often progressively results in aberrant signaling between tubular epithelium and the surrounding non‐tubular cell types, ultimately leading to chronic kidney disease.
‘BET Inhibtion in Kidney Fibrosis’ funded by the Austrian Science Fund.
Enhancer and super‐enhancer dynamics in repair after ischemic acute kidney injury. Wilflingseder J, Willi M, Lee HK, Olauson H, Jankowski J, Ichimura T, et al. Nat Commun. 2020;11(1):3383.
Interferon‐regulated genetic programs and JAK/STAT pathway activate the intronic promoter of the short ACE2 isoform in renal proximal tubules. Jankowski J, Lee HK, Wilflingseder J, and Hennighausen L. bioRxiv. 2021.
Graduate student: Jakub Jankowski, MSc
Lothar Hennighausen, NIDDK, National Institute of Health, Bethesda, MD, USA
Joseph V. Bonventre, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Publications (short link)