Dr. Li of the Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University studies a high-risk subtype of B-Cell ALL, occurring in about 15% of B-Cell ALL patients that is dependent on the activity of a signaling pathway, JAK2, but is resistant to classical Jak2 inhibitors (Type I), due to several acquired mutations. A Type II JAK2 inhibitor shows promise in mouse models of B-Cell ALL, increasing overall survival and reducing cancer growth but cannot be tested in humans due to its poor chemical properties.
Dr. Li will identify alternatives to this compound that can be developed for use in human clinical studies. Dr. Li will use two strategies: first, she will test a panel of novel type II JAK2 inhibitors and second, a panel of compounds that selectively degrade JAK2 within cancer cells (JAK2 degraders) in B-Cell ALL cells and animal models.
In the first year, Dr. Li expects to identify 2-3 lead compounds for further drug development. She will determine their suitability for human clinical studies by the end of the second year. By the end of year three, she expects to initiate drug development work with the goal of translating her research into pediatric clinical trials.