PhD Degree for Lotte Tholen

Lotte Tholen successfully defended her thesis entitled ‘Capturing HNF1β-mediated gene expression in the kidney’.

Outline of this thesis
Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor involved in the development and homeostasis of many epithelial tissues including the liver, kidney, pancreas and intestines. In the kidney HNF1β is responsible for cell-type specific gene expression of renal transporters, signaling molecules and differentiation genes. Genetic defects in HNF1B cause a dominantly inherited, multisystem disease called autosomal dominant tubulointerstitial kidney disease type HNF1β (ADTKD-HNF1β). Patients suffer from renal malformations, cyst and/or electrolyte disturbances including hypomagnesemia, hypocalciuria and hypokalemia. Extrarenal phenotypes consist of diabetes, gout and neurodevelopmental disorders. The clinical presentation of the disease is highly variable and currently the type mutation has no predicate value for development of diabetes or need for renal replacement therapy. Therefore, correctly diagnosing patients and predicting disease progression is challenging. Over the years HNF1β-mediated transcription in the kidney has been implicated in pathways including renal metabolism, cell polarity, kidney development and ion transport. However, the spectrum of HNF1β-target genes is currently incomplete and therefore key players in the molecular mechanism of the disease are likely missing. In this thesis, we have investigated transcriptional regulation governed by HNF1β in the kidney and studied the importance of co-factor binding and 3D genome conformation in this process. 

Biography
Lotte Tholen (1994) obtained her master’s degree in Molecular Mechanisms of Disease (MMD) in 2017 from the Radboud Institute for Molecular Life Sciences (RIMLS), Radboudumc in Nijmegen. During her PhD research Lotte investigated gene expression regulation by transcription factor HNF1β in the kidney. Lotte presented her findings by oral and poster presentations at national and international conferences such as the Dutch Nephrology days in Veldhoven and the Experimental Biology meeting (online). Moreover, she was awarded a travel grant by the RIMLS to attend and present a poster at the EMBO workshop on enhanceropathies in Santander (Spain).