My lab has focused on the identification of novel genes and pathways regulating hematopoiesis and the role of these genes in malignancy. We have cloned and characterized the tyrosine kinases CHK (MATK) and RAFTK/PyK2 as well as the tyrosine phosphatases PTPRO and PTP-NP, and identified new members of the Kelch related proteins (NRPB, Mayven and MRP2). We have also elucidated the signaling pathways mediated by the tyrosine kinases, CSK, CHK, SRC, FAK, RAFTK/Pyk2, ErbB-2 and VEGF receptors in breast cancer cells and their roles in tumorogenesis and metastasis.

In addition, we investigated the physiological functions of the endocannabinoid system in regulating hematopoiesis and hematopoietic stem cell functions. Endocannabinoids are arachidonic acid derivatives and part of a novel bioactive lipid signaling system, along with their G-coupled receptors (CB1 and CB2) and the enzymes involved in their biosynthesis and degradation. We have examined the expression of endocannabinoids in the BM niche and the expression and function of CB1 and CB2 cannabinoid receptors in human and murine HSPCs. We reported that the CB2/CB2-agonist axis is involved in hematopoiesis and induces chemotaxis and colony formation upon ligand stimulation. In vivo, the CB2 agonist AM1241 causes mobilization of murine HSPCs with short- and long-term repopulating abilities. Future studies in my group will explore the role of the endocannabinoid system in engraftment, homing and the therapeutical potential of CB2-based cannabinoids in bone marrow transplantation and BM recovery after insult. In addition, we plan to examine whether CB2 agonists disrupt the interaction of multiple myeloma cells with the BM niches and enhance their sensitivity to therapy. We aim to determine the physiological functions of the endocannabinoid system and its role in hematopoiesis, under steady-state conditions and post-stress conditions. Additionally, we aim to examine the potential of CB2 agonists in sensitization of myeloma by mobilization.