Dr. Kim was recently awarded a 2025 TAMU-PVAMU PRISE (Panther Research & Innovation for Scholarly Excellence) Grant in collaboration with Dr. Hamed Ali Ismail (TAMU). This is a 20-month grant (October. 2025 - May 2027) to encourage collaborative research between Texas A&M University and PVAMU faculty. The TAMU PI will receive a grant in the amount of $20,000 from the TAMU Division of Research, while the PVAMU PI will receive $20,000 from PVAMU.
Project Title: Sequential Targeting of Alzheimer’s Disease by Novel Gamma-Secretase Modulator and Fyn Kinase Inhibitor
Principal Investigator: Seungchan Kim, Ph.D. (PVAMU) and Hamed Aly Ismail, Ph.D. (TAMU)
Project Summary:
This study addresses the urgent need for effective treatment of Alzheimer’s disease (AD) by sequential targeting of g-Secretase and Fyn kinase. Currently, AD therapies have been largely ineffective, prompting the need for novel therapeutic approaches. g-Secretase modulators (GSMs) offer a compelling alternative to g-secretase inhibitors (GSIs) in selectively modulating Aβ generation without inhibiting Notch1 cleavage, which is associated with major adverse effects. While no selective Fyn kinase inhibitors (KIs) exist, this study aims to develop Fyn inhibitors to mitigate off-target effects. This proposal includes the integration of computer-aided drug design (CADD) to craft selective Fyn kinase inhibitors and the utilization virtual high-throughput screening (vHTS) to identify GSMs with enhanced selectivity. Poor 2D and animal models of disease contribute to the 90% failure rate in clinical drug testing. Therefore, we will develop a 3D, cell culture, brain organoid-based model of Alzheimer’s disease. This proposal will afford a superior prognosis of AD by prioritizing safety and selectivity to improve the quality of life of individuals affected by AD, thus positively impacting our society. These outcomes will be utilized to apply for R21/R01 NIH funding and will have a translational impact on establishing novel therapeutic interventions for treating AD.