Barnabas Ilenwabor successfully defended his thesis entitled ‘Exploring novel regulatory pathways in renal magnesium homeostasis’.
Outline of this thesis
The aim of this thesis is to provide further identify and characterize the molecular mechanisms of the regulation of systemic Mg2+ homeostasis by novel regulatory pathways and to provide additional evidence for the role of established pathways in systemic Mg2+ regulation. Development of in vivo models is essential to further increase our understanding how Mg2+ is reabsorbed in health and in disease. Chapter 2 aimed to elucidate the function of FAM111A using knockout mouse models. The generated FAM111A knockout mice were subjected to metabolic cage studies and characterized to understand the importance of FAM111A in regulating systemic Mg2+ levels. This would provide translational value in elucidating the electrolyte disturbance in KCS2. In chapter 3, we further characterized novel pathways/ targets involved in the KCS2 disease. RNA-sequencing and affinity pulldown/mass spectrometry was performed to identify targets and interating partners of FAM111A protein. Our data identified STAT1 as a novel binding partner for FAM111A. In chapter 4, the relationship between the classical immune pathway STAT1 and renal Mg2+ handling was investigated. By employing genetic mouse models, in vitro models, and in patient with immunodeficiencies, the role of STAT1 in regulating Mg2+ balance was studied and the relevance of this regulatory pathway was also explored. Chapter 5 examined the role of SLC41A1 as the basolateral Mg2+ extrusion protein in mammalian models by employing SLC41A1 knockout mice. Mice lacking both SLC41A1 and SLC41A3 were used to investigate redundancy between SLC41A1 and SLC41A3.
Biography
Barnabas Ilenwabor is a PhD candidate at the Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands. His PhD research focuses on the regulation of renal Magnesium transport in health and rare monogenetic tubular disorders under the supervision of Prof. Dr. Joost Hoenderop and Dr. Jeroen de Baaij. In his spare time, Barnabas enjoys watching sporting activities like football, Formula 1, and tennis.