Project: Defining CK2-dependent neuronal membrane disorganization as a disease mechanism and biomarker in Okur-Chung Neurodevelopmental Syndrome
Lead Investigator: Thuy Vien, PhD, MBA | Northwestern University
Grant Details:
Project funded for one year starting in 2026 for a total of $50,000.
Aims of Grant:
Although it is known that individuals with OCNDS have neurological symptoms, there is currently no cell-based experimental system that connects specific patient variants in CSNK2A1 with measurable readouts in neurons. Such a system could be used to better understand the biology of different variants and for early testing of therapeutics.
This project proposes that OCNDS does not only alter the activity of CK2, a kinase, which acts like a switch to turn other proteins on or off. It may also affect the organization of the neuronal membrane by regulating binding regions on parts of sodium channels, the proteins that allow electrical signals to pass through the neuronal membrane.
The region of the membrane where CK2 is thought to play a role is important for initiating and stabilizing action potentials, the brief electrical signals that travel along a neuron to send messages to other neurons. Dysfunction in this region may explain some of the neurological features of OCNDS and could serve as a readout for how effective future therapies are.
First, this study will investigate how patient variants in CSNK2A1 alter the organization of the neuronal membrane using patient-derived induced pluripotent stem cells (iPSCs), which are adult cells reprogrammed into a stem-cell state that can differentiate into nearly every cell type. The iPSCs will be differentiated into neurons, and the neurons will be imaged using high-resolution microscopy.
The information gained from the first aim will be used to develop a metric called the “membrane organization score,” a single number that summarizes the most informative features seen in the images. The team will then test how this score changes when CK2 function is disrupted or restored, with the goal of developing an imaging-based biomarker, a measurable indicator of a biological state or a response to treatment.
The results of this project will produce a standardized laboratory test in human iPSC-derived neurons that will allow different CSNK2A1 variants to be linked with specific, measurable physical characteristics in neurons, potentially serving as a biomarker for future therapeutic pipelines.