The Rannar Airik laboratory focuses on identifying the genetic and molecular mechanisms of chronic kidney disease (including renal ciliopathies), that may be targetable by therapy. To achieve this, the lab combines transgenic animal models and biochemical assays that provide a basis for further molecular dissection of the mechanisms involved in these human diseases.
Chronic kidney disease
Chronic kidney disease is a devastating condition that affects an increasing number of people in the world. It leads to a progressive loss of kidney function in affected individuals and ultimately necessitates dialysis or kidney transplantation for survival. My lab has demonstrated that impairment of DNA damage response in the kidney tubular epithelium can lead to kidney tubular injury and precipitate progressive fibrotic changes in the kidney, culminating in loss of kidney function. Investigating the role of DNA damage response in normal tubular maintenance, and assessing how its deficiency underpins chronic kidney pathology is a high priority of our work.
Renal ciliopathies are a group of fibrocystic kidney diseases that are caused by structural or functional defects in the primary cilium – a whiplike cell-surface organelle, that regulates the activity of several cellular signaling pathways. Accordingly, mutations in ciliary genes, such as those encoding nephrocystins/NPHP-proteins, compromise the cilium, and result in fibrocystic kidney pathology. Although, being a major genetic cause of childhood end-stage kidney disease, the pathomechanisms underlying NPHP are not well understood. To get better insights into the disease mechanisms, and to develop therapies against this condition, we use transgenic animal models and cell culture systems.
Chaki M*, Airik R*, Ghosh AK, Giles RH, Chen R, Slaats GG, Wang H, Hurd TW, Zhou W, Cluckey A, Gee HY, Ramaswami G, Hong CJ, Hamilton BA, Červenka I, Ganji RS, Bryja V, Arts HH, van Reeuwijk J, Oud MM, Letteboer SJF, Roepman R, Husson H, Ibraghimov-Beskrovnaya O, Ysunaga T, Walz G, Eley L, Sayer JA, Schermer B, Liebau MC, Benzing T, Le Corre S, Drummond I, Joles JA, Janssen S, Allen SJ, Natarajan S, O’Toole JF, Attanasio M, Saunier S, Antignac C, Koenekoop RK, Ren H, Lopez I, Nayir A, Stoetzel C, Dollfus H, Massoudi R, Gleeson JG, Andreoli SP, Doherty DG, Lindstrad A, Golzio C, Katsanis N, Pape L, Abboud EB, Al-Rajhi AA, Lewis RA, Lupski JR, Omran H, Lee E, Wang S, Sekiguchi JM, Saunders R, Johnson CA, Garner E, Vanselow K, Andersen JS, Shlomai J, Nurnberg G, Nurnberg P, Levy S, Smogorzewska A, Otto EA and Friedhelm Hildebrandt. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell 150:533-548, 2012 *Co-first authors.
Airik R, Slaats G, Guo Z, Weiss AC, Khan N, Ghosh A, Hurd T, Bekker-Jensen S, Schrøder J, Elledge S, Andersen J, Kispert A, Castelli M, Boletta A, Giles R, Hildebrandt F. Renal-retinal ciliopathy gene Sdccag8 regulates DNA damage response signaling. JASN 25:2573-2583, 2014.
Insolera R, Shao W, Airik R, Hildebrandt F, Shi SH. SDCCAG8 regulates the pericentriolar material recruitment and neuronal migration in the developing cortex. Neuron 83:805-822, 2014.
Airik R*, Schueler M, Airik M, Cho J, Porath JD, Mukherjee E, Sims-Lucas S, Hildebrandt F*. A FANCD2/FANCI-Associated Nuclease 1-Knockout Model Develops Karyomegalic Interstitial Nephritis. JASN 2016, 2016 Mar 29. ASN.2015101108. *Co-corresponding authors.
Airik R*, Schueler M, Airik M, Cho J, Ulanowicz KA, Porath JD, Hurd TW, Bekker-Jensen S, Schrøder JM, Andersen JS, Hildebrandt F*. SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling. PLoS One 2016 11(5):e0156081. *Co-corresponding authors.
Opportunities in the Airik Lab
We are always welcoming applications from enthusiastic students or postdocs looking to work with us. For more information, please email firstname.lastname@example.org.