Research group Regulation of epithelial electrolyte transport

Characterization

Through uniquely synergizing cutting-edge (bio)chemical and biophysical technologies, we aim to deliver detailed insight into epithelial ion channels (mainly TRP channels) and transporters. This will unravel structural domains and regulatory subunits essential for their function, which aids in unravelling the pathogenicity of specific disease variants and can provide detailed insight into the actions of pharmacological compounds, to ultimately support drug development programs.

Understanding

The urinary calcium concentration is an important factor in kidney stone formation, and it is evident that avoidance of new crystal deposits should be the prime target site in order to prevent recurrence. Here, we focus on gaining fundamental knowledge on the related process of how perturbations in tubular calcium transport induce kidney stone formation. In addition, we aim to develop of a new molecular entity with a unique mode of action that might in the future be used for effective treatment of kidney stones.

Kidney organoids

Organoids constitute self-renewing 3D cultures that retain many structural and functional properties exhibited by the organ of origin. Kidney organoids may serve as disease model, provide new drug screening opportunities, and exhibit a high potential for treatment of renal disorders such as inherited electrolyte disorders. Therefore, it is essential to gain better understanding of electrolyte transport and its molecular regulation in kidney organoids. We are currently optimizing organoid culture and evaluating the transport of several electrolytes (Na+, Ca2+, Mg2+) in different types of kidney organoids (i.e. induced pluripotent stem cell (iPSC)-derived, adult stem cell-derived). 
 

Grants and prizes

• NWO ENW KLEIN: “Calmodulation of the epithelial calcium channels TRPV5 and TRPV6: Untangle a dual-faced mechanism”
• ZonMW Off Road for Sara Roig: “Smart-therapy for polycystic kidney disease: a urine-based drug repurposing study” (2020)
• Radboudumc PhD fellowship for Emre Dilmen: “Towards a functioning kidney-on-a-chip” (2020)
• RIMLS Junior Researcher (PhD) grant (2020) “Klotho in the kidney: a hormone goddess or still a myth”, co-supervised with Joost Hoenderop
• Radboud University study prize for Mark van Goor (2019)
• Radboudumc PhD fellowship for Wouter van Megen: “Flow sensing and electrolyte reabsorption in ciliary dysfunction” (2019)
• Marie Curie Individual fellowship for Sara Roig: “Flow-stimulated ion channel signalling in renal epithelia (2019)
• Fundación Alfonso Martín Escudero post-doctoral fellowship for Sara Roig: Calmodulin regulation of the calcium channel TRPV5 (2018)
• Radboudumc PhD fellowship for Mark van Goor: “TRPV structure and function: mechanistic insight into the functional diversities of TRPV ion channels” (2018)

In the media

• Radboudumc news: TRPV5 cryo-EM structure
• NierNieuws news: Kolff Battle of the Universities
• NierNieuws news: ZonMW Off Road project