Human Cell-Based Models for Bridging the Gap Between Genetics and Pathology

Our team is trying to transform how we study the pathophysiological links between genetic risk pathways and molecular pathology. We seek to build a new discovery platform by studying linked in vitro models and post-mortem tissues from the same individual patients. We will use high-dimensional histologic and transcriptomic profiling, analyzed through innovative machine learning-based methods, to identify shared phenotypes within each paired system and across methods and patients. Candidate mechanistic pathways that emerge will have high disease-relevance and robustness due to the human-based and methodologically convergent nature of the strategy. Those candidate mechanisms will then flow naturally into human cell models for perturbation and treatment-related experiments. If successful, this work could begin to provide a new approach for identifying, validating, and pursuing potential therapeutic targets for neurodegenerative disease.