My research interest is focused on understanding how protein arginine methylation by PRMT`1 regulates megakaryopoiesis and thrombopoiesis at molecular levels. Dysregulated megakaryocytes and their platelet progenies by PRMT1 play critical roles in hematological malignancies including leukemia and pre-leukemia diseases such as myeloid proliferative neoplasm and myelodysplasia syndrome (MDS), as well as in cardiovascular diseases and cancers.

1. To understand PRMT1-mediated molecular pathways in the generation of immune megakaryocytes and regulation of their functions.
   For the last ten years, we have systematically characterized a few proteins (RUNX1, RBM15 and DUSP4) involved in megakaryopoiesis are methylated by PRMT1. These proteins are indispensable for normal megakaryopoiesis. Mutations in RUNX1 are frequently found in leukemia and familial platelet disorders associated with myeloid malignancies. RBM15 is involved in a chromatin translocation t(1:21) in acute megakaryocytic leukemia. DUSP4 dephosphorylates p38 kinase which is often activated in myelodysplasia syndrome. Activation of p38 kinase often occurs in inflammatory response and stress hematopoiesis. From our single cell RNA-seq analysis and transgenic PRMT1 mouse models, our preliminary data support that PRMT1 upregulation blocks the differentiation into normal megakaryocytes but tilts the differentiation into immune megakaryocytes (Mks).
   
   

   Currently, my lab is focused on characterizing the functions of immune Mks regulated by PRMT1. Immune Mks are found in sepsis patients. Mouse studies from several groups including ours discovered that immune Mks can present antigens to T cells. Characterizing immune Mks may open up new avenues for disease treatment and write new chapters for immunology.

2. To understand pathogenic platelets in creating a tumor-friendly microenvironment.
   Upregulation of PRMT1 is associated with diabetes, cancers and bacteria infections. Our preliminary data demonstrated that upregulation of PRMT1 in Mks produce platelets which contain higher levels of RNA and express CD62 the platelet activation marker in higher percentage of platelets. In addition, we found the platelets (our definition of pathogenic platelets) are hyperactive in aggregation and contain higher levels of proteins such as proinflammatory cytokines. The PRMT1 transgenic mice are predisposed to develop ovarian cancer when transplanted with mouse ovarian cancer cells. Currently we are investigating whether immune Mks and pathogenic platelets promote ovarian cancer progression using mouse models and human samples.