Abstract: Drug combinations have the potential to greatly expand our pharmacopeia while reducing both cost and drug resistance. Yet the current drug-discovery approach is unable to screen the astronomical number of possible combinations in different cell types and does not account for the complex environment inside the body. We have developed AI tools - INDIGO and MAGENTA - that predict the efficacy of drug combinations based on the properties of the drugs, the pathogen, and the infection environment. We are also using modeling to identify drugs that work in synergy with the host immune system. Using INDIGO and MAGENTA, we have identified highly synergistic combinations of repurposed drugs to treat drug resistant infections including Tuberculosis, the deadliest bacterial infection. INDIGO also accurately predicts the outcome of past clinical trials of drug combinations. Our ultimate goal is to create a personalized approach to treat infections using AI.
Biography: Chandrasekaran received his bachelor’s degree in Biotechnology from Anna University in 2008, and a PhD in Biophysics from the University of Illinois at Urbana-Champaign in 2013. He worked at Harvard University and MIT as a Harvard Junior Fellow between 2013 and 2016 and became an Assistant Professor at UM in 2017. His lab develops systems biology algorithms for drug discovery. Computer models from his lab like INDIGO and MAGENTA are being used to design effective therapies against drug resistant pathogens. His lab also develops systems biology algorithms to understand metabolic regulation. The approaches that they have created (PROM, ASTRIX, DFA, EGEM and GEMINI) perform complementary functions in modeling of metabolic and regulatory networks. Chandrasekaran’s research has been published in Cell, Genome Biology, mBio, and PNAS. For his work, Chandrasekaran previously received the 2013 Harvard Junior Fellowship, the 2011 Howard Hughes Medical Institute (HHMI) International Predoctoral Fellowship, the 2014 William Milton Fund award, 2018 UM Precision Health Investigator Award, and the 2018 Distinguished Young Investigator Award from the AICHE COBRA society.