Ismael Al-Ramahi, Ph.D.

Research Focus: High-throughput genetic and drug screens

My group specializes in the integration of computational approaches with high-throughput screens in order to identify therapeutic targets, pharmacological agents and risk or protective genetic factors for neurodegenerative diseases.

Part of our research focuses on dominantly inherited polyglutamine diseases using Drosophila and cell-based models to perform genetic screens followed by validation in mice and human patient samples. This work has led to the identification of previously unknown links between different neurodegenerative diseases. We also target the “druggable genome”. In this line, we have uncovered novel therapeutic targets that could improve proteostasis, lowering the levels of the culprit proteins in neurodegenerative diseases, one of the most attractive therapeutic approaches being pursued by academia and industry.

In the context of Alzheimer’s disease, we leverage the growing number of patient transcriptomic, proteomic and genomic datasets that are becoming available. Using computational methods we identify candidate genes. This is followed by state-of-the-art behavioral screening in Drosophila (using a robot assisted platform) and cells to assess the effect of each of these genes on age-related neurodegeneration. The most promising candidates are pursued using mouse models. This work has revealed transcriptomic signatures that are neuroprotective in Alzheimer’s and identified mutations that influence the risk of developing Alzheimer’s disease, including many protective variants. 

Women are twice as likely as men to suffer from Alzheimer’s. One specific area of our research targets the identification of sex-specific genetic factors that influence Alzheimer’s risk. We use Drosophila, cell-based and mouse models of Alzheimer’s to identify and characterize the mechanisms of action of female-specific risk and protective genes. One of the projects focuses on a particularly intriguing gene involved in DNA quality control, which could link Alzheimer’s and breast cancer, another condition predominant in females.