Gloria Lee, PhD, Professor of Internal Medicine in Immunology, and Thimmasettappa Thippeswamy, DVM, PhD, Professor of Biomedical Sciences at Iowa State University, have been awarded a two-year, $50,000 seed grant supported by the University of Iowa’s Office of Research and Economic Development (ORED) and the Office of the Vice President for Research at Iowa State University. Their intermural collaboration is one of five such grants announced last month.

Drs. Lee and Thippeswamy, along with UI co-investigators Dr. Alexander Bassuk, Professor of Pediatrics, and Dr. Marco Hefti, Assistant Professor of Pathology, will examine the effects and interactions of proteins Tau and Fyn in an Alzheimer disease-related pathway in epileptic seizures.

There is an observed increased incidence of seizures in Alzheimer’s disease, and Tau protein pathology, a hallmark feature in Alzheimer’s disease, has also been found in epilepsy. Fyn, a protein tyrosine kinase, is critically involved in numerous biological processes, including synaptic function, and has also been connected to Alzheimer’s disease.

Dr. Lee’s laboratory was the first to recognize that Tau interacted with Fyn and that the interaction had a role in Alzheimer’s disease. To investigate further, her lab has developed a mouse model deleted for both Tau and Fyn. She and Dr. Thippeswamy, an established epilepsy researcher, have been examining mouse models deleted for Tau, Fyn, or both, to determine how these deletions affect seizure activity.

The collaboration between the two labs will examine the role of Tau-Fyn signaling in epilepsy, testing the hypothesis that during a seizure, the Tau-Fyn complex activates the neuronal NMDA receptor/PSD95 pathway, resulting in hyperexcitability of neurons and seizures. Using the different mouse models, the complex between NMDA receptor and PSD95 will be examined before and after seizure induction. The seizures will also be monitored using continuous video-EEG acquisition, allowing correlations to be made between characteristics of the seizure and the presence/absence of Tau, Fyn, and NMDA receptor-PSD95 complexes. Lastly, human serum and tissue samples will be examined for the presence of abnormal Tau and complexes of Tau-Fyn and NMDA receptor-PSD95. 

This is the first year that collaborations such as this have been funded by the two schools. By combining each university’s complementary strengths, the two institutions hope that successes will spur more cross-site interactions, further discoveries, and create opportunities to win larger grants.