Dr. Loretta Li – Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University
CureSearch Young Investigator Award: 2018-2020
Focus: High-risk B-cell Acute Lymphoblastic Leukemia
Project Title: JAK2 inhibition and degradation in B-cell acute lymphoblastic leukemia
Project Overview: Dr. Li 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.
“I am incredibly grateful for CureSearch’s support. This funding came at a critical juncture in my career as I made the transition from trainee to independent investigator,” shared Dr. Li. “I am optimistic that our work will lead to new targeted agents that can be translated to clinical trials for pediatric patients with high-risk leukemia.”
Project Update: As of September 2020, Dr. Li has transitioned from the Dana-Farber Cancer Institute to a tenure-track faculty position at Northwestern University. In addition to establishing her new lab, she has validated on-target binding of her JAK2 inhibitors, demonstrating that they are properly interacting with the desired target in B-cell ALL. She is also building a collaboration with GlaxoSmithKline in order to test their JAK2 degraders in JAK2-dependent leukemia cell lines and determine if they will serve as a treatment strategy in high-risk JAK2-dependent B-cell ALL.