Qingfei Jiang, PhD

Cancer relapse can occur months or years after the primary cancer was treated. Recurrent cancer is extremely more difficult to eradicate and more aggressive. In the case of pediatric T-ALL, only 1 out of 4 kids survive the intense treatment. We now understand that relapsed T-ALL is enriched with leukemia initiating cells (LIC). LIC are rare cells that possess many stem cell-like properties. Uncovering the mechanisms by which LIC gain these abilities are critical for identifying targeted approaches to developing curative therapies. Seminal discovery showed that ADAR1-directed RNA mutations is required for LIC expansion. In fact, loss of ADAR1 completely eliminate LIC and prolong survival in patient-derived models. However, no agents directly inhibiting the ADAR1 have successfully advanced to the clinic. Here, we propose to investigate a novel ADAR1-targeting antisense oligonucleotides (ASOs) as therapeutics for this devastating disease. My laboratory focuses on clinical grade patient samples, a patient-derived co-culture system and patient-derived xenograft models to examine our hypothesis. If successful, this discovery will lead to the development of novel therapeutic strategies and quick translation into clinical trials for relapsed patients. This new endeavor will provide a valuable opportunity to continue our work with the shared goals of improving the lives of pediatric T-ALL and potentially other pediatric malignancies.