Current Research Projects
The Lynn Lee Lab's research is focused on elucidating the mechanisms driving childhood leukemias using functional genomics and cutting-edge molecular biology techniques. Our specific areas of research are as follows:
MBNL1-mediated RNA processing in MLL-rearranged acute leukemia
Our laboratory recently described how we found the RNA binding protein MBNL1 to be highly upregulated in MLL-rearranged leukemia. We subsequently showed that knockdown of MBNL1 preferentially resulted in MLL-rearranged leukemia cell death, and in collaboration with Dr. Nathan Salomonis, showed a characteristic missplicing signature that included key genes involved in MLL leukemia pathogenesis. We are continuing to investigate and better understand our observations using technologies such as long-read sequencing and CLIP-seq. Furthermore, we are developing assays to screen compound libraries for small-molecule inhibitor candidates, with the eventual goal of developing a clinical candidate.
Target discovery with in vivo CRISPR screening in leukemia xenografts
In collaboration with the lab of Dr. Jim Mulloy and their expansive collection of pediatric leukemia xenografts, we have developed methods to optimally perform targeted CRISPR screens in vivo in order to identify novel dependencies and thus therapeutic targets. Our focus has been on high-risk leukemias, such as ETO2/GLIS2-rearranged acute megakaryoblastic leukemia.