Naomi Dirckx, PhD
Assistant Professor, WashU Orthopedic Surgery
- Phone: 314-362-8597
- Email: dirckx@nospam.wustl.edu
The role of citrate transport in epilepsy
My lab’s research focuses on understanding the function of the membranous citrate transporter Solute Carrier Family 13 Member 5 (SLC13A5) both at the tissue level as well as systemically. Initially interested in its role in skeletal mineralization due to my background as a bone biologist, my research group investigates how mineral incorporation of citrate affects bone quality during growth and aging, as well as the impact of alterations in skeletal citrate uptake on systemic citrate homeostasis and calcium balance. While studying SLC13A5, I became involved with the TESS Research Foundation, and started collaborating with other scientists and conducting research on primary teeth and human induced pluripotent stem cells (hiPSCs) from individuals with mutations in the SLC13A5 gene and healthy siblings.
Through this work and my interaction with affected families, I developed an interest in another non-skeletal manifestation associated with SLC13A5 mutations, namely epilepsy. Currently, the metabolic signature of neurons with deficient SLC13A5 transporters and the underlying cause of epilepsy remain unclear. To shed light on the mechanisms behind the seizures, I was funded by the CURE epilepsy partnership award in early 2024.
By using a metabolomics approach and 13C-NMR, we will investigate alterations in neuronal metabolism and metabolite trafficking between astrocytes and neurons in SLC13A5 deficient mouse brains respectively. In particular, we believe that the mechanism of metabolite trafficking is affected by SLC13A5 deficiency as we observed that osteoblast that lack this transporter release an increased amount of citrate to the expense of glutamine production. If astrocytes employ a similar mechanism, epilepsy could be evoked by 1) reduced glutamine trafficking to neurons leading to impaired neurotransmitter generation and 2) increased levels of citrate in the synaptic cleft modulating NMDA receptors.