Jennifer L. Wilson, Ph.D.
Assistant Professor of Bioengineering
University of California Los Angeles
Faculty Host: Andrew McCulloch, Ph.D.
Seminar Information
Already, we understand that drugs can have multiple effects on disease symptoms and side-effects, and further that they often act through on- and off- target protein binding, yet we underutilize this information at initial drug design or when prescribing. We previously discovered that reclassifying drugs by their effects on proteins downstream of known drug targets can better predict clinical effects. In this study, we developed a novel ALS-focused protein interaction analysis using datasets collected from patient samples, the public domain, and consortia. We used these pathways to design new drug classes, and assessed class-level effects on ALS overall survival in a retrospective analysis of real-world data. With complementary in vitro analysis, we observed that drugs that induce complement activation are associated with increased risk for death, implicating this pathway as a viable therapeutic target for treating ALS. We further extended our approach to search for six protein classes, three of which, including multiple chemokine receptors, had more significant effects on ALS survival, suggesting that targeting proteins such as chemokine receptors could be advantageous for these patients. We also tested four drug classes in Parkinson’s and Myasthenia Gravis. We again recovered effects for drugs associated with complement activation and discovered that drugs associated with chemokine receptors had stronger effects on overall survival. Taken together, these results demonstrate the utility of a network medicine approach for testing novel therapeutic effects using real world data and suggest actionable therapeutic strategies for multiple neuroinflammatory diseases. In addition to insights about neurodegeneration, this suggests a framework for understanding altered disease biology in patients taking medications consistently.
Dr. Jennifer L. Wilson is an Assistant Professor at the UCLA Department of Bioengineering. With the Lab for the Understanding of Network Effects (LUNE), Dr. Wilson studies how proteins downstream of drug targets affect drug-induced phenotypes – the ability to mitigate disease or cause side effects. The lab aims to develop engineering principles for rationally designing novel drug targets by accounting for downstream protein effects. Prior to coming to UCLA, Dr. Wilson earned a B.S. in Biomedical Engineering at the University of Virginia, she was an NSF Graduate Fellow with Doug Lauffenburger at M.I.T., and recently completed a CERSI fellowship in Regulatory Science (with Russ Altman) and SPARK fellowship (with Kevin Grimes) at Stanford University.