Benjamin Readhead

My research is focused on developing and applying integrative genomics approaches to high-dimensional biomedical data with the goal of improving therapeutic options for patients with neurodegenerative diseases, particularly Alzheimer's disease. Broadly speaking, my efforts have approached these areas using two complementary conceptual frames. The first, is a “disease-centric” frame, involving the integration of diverse data-driven methods with DNA sequence, transcriptomic, proteomic, metabolomic and clinical data, to build rich, multiscale network models that capture important causal relationships relevant to disease, which can then be systematically mined to prioritize potential therapeutic opportunities for further experimental validation. 

The second frame, is a “therapy-centric” approach, which typically involves a variety of computational drug discovery and repositioning methods, that encompass unbiased surveys across thousands of high-dimensional drug signatures (such as drug induced transcriptional signatures) to identify novel candidate disease indications for existing and approved therapies. In the course of refining and applying these methods, I am fortunate to have been involved in drug discovery and repositioning projects across many therapeutic areas, including Alzheimer’s disease, dystonia, schizophrenia, Niemann-Pick C, cardiometabolic disease, prostate cancer, multiple myeloma, chronic kidney disease, non-alcoholic steatohepatosis, idiopathic pulmonary fibrosis, dermatology and infectious diseases.

The combination of these two frames enables a very integrative, and systems-minded series of efforts aimed at developing and applying integrative computational approaches to high- dimensional biomedical data for the goal of improving therapeutic options for patients with neurodegenerative diseases, especially Alzheimer's.

A major focus of my work is aimed at understanding the potential impact of common pathogens on the risk or progression of Alzheimer’s disease. Important roles for microbes and antimicrobial defenses in the pathogenesis of Alzheimer’s disease have been suspected for over 100 years, although findings have been conflicting, and a consistent association with specific microbial species has not emerged. I am especially interested in helping to disentangle the complex web of interactions between the peripheral infections, the brain microbiome and host biology in the context of neurodegenerative disease to better understand the earliest drivers of disease and use these findings to discover novel therapeutic strategies.