|Address:||Shelby Biomedical Rsch Building
19th Street South
Birmingham, AL 35294-0024
|Areas of Focus: My long-term research focus is on the molecular basis of normal hematopoiesis and hematological
malignancies including leukemia and pre-leukemia diseases such as myeloid proliferative neoplasm and myelodysplasia
1. To understand PRMT1-mediated metabolic reprogramming in leukemogenesis. In the Elife paper, we elucidate that protein arginine methyltransferases 1 (PRMT1) methylates an RNA binding protein called RBM15 and thus controls the RBM15 protein stability. RBM15 regulates the stress response of hematopoietic stem cell for self-renewal, and is involved in chromosome translocation with MKL1 in acute megakaryocytic leukemia (AMKL). I have established several metabolic assays to monitor PRMT1-RBM15 regulated metabolic changes in cell culture systems as well as in a mouse model for acute megakaryocytic leukemia. In this project, I will address the hypothesis that the PRMT1-RBM15 axis regulates metabolic pathways, which is the key for leukemia progression.
2. To understand RBM15-mediated RNA splicing pathways in MDS. We have demonstrated that alternative RNA splicing of a few key transcription factors pivotal for hematopoiesis is regulated by the PRMT1-RBM15 axis. In collaboration with Dr. Christina Leslie’s lab at Memorial Sloan Kettering Cancer Center, my second project is to decipher the RNA splicing codes regulated by the PRMT1-RBM15 axis, which may play a pivotal role for MDS. Given that more than 70% of MDS have mutations in splicing factors, understanding the RNA splicing codes will hold a key to design precision medicine for MDS. Besides bioinformatics analysis of RBM15 binding sequences at transcriptome-wide level, my lab has been working on the new mechanism of transcription-couple RNA splicing regulated by the PRMT1-RBM15 axis.
3. To understand how RBM15 protein translation is regulated by a long noncoding RNA (AS-RBM15). This project is based on our paper in EMBO Reports. Given that little is known about the biological roles of long noncoding RNAs in hematology, the endeavor in my lab will open up new frontiers to understand hematopoiesis and cancer.
In summary, my research is centered on the PRMT1-RBM15 axis for its molecular roles in hematopoiesis and for targeting the downstream genes in this axis for treating leukemia and other pre-leukemia diseases. In the next five years, I expect to make major breakthroughs on how metabolic reprogramming in leukemogenesis is regulated via arginine methylation of RBM15 and DUSP4 by PRMT1; and how anti-sense long noncoding RNA AS-RBM15 regulates hematopoiesis. In the translational medicine front, I expect to develop strategies for using PRMT1 inhibitors for cancer treatment.