Motor proteins in platelet and RBC biology
Non-muscle myosin II (NMII) is the crucial motor proteins that drive mitotic division and regulate the transition from mitosis to endomitosis in megakaryocytes. This process is a crucial determinant of the size of the megakaryocytes and consequently the number of platelets that are extruded by each megakaryocyte. NMII also regulates erythroid enucleation. We study the regulation of NMII motor proteins in the context of platelet and RBC biology. By understanding the impact of actin remodelling pathways on NMII localization and function we can modulate the maturation of megakaryocytes and erythroblasts. READ MORE
Thrombopoietin receptor dynamics in health and disease
Thrombopoietin receptor (TpoR) drives the development of megakaryocyte lineage. TpoR is also important for the maintenance of haematopoietic stem cells (HSCs). Platelet surface TpoR also maintains homeostasis by regulating the serum thrombopoietin levels. Thus, the dynamics of TpoR cell surface expression, internalization and redirection of internalized TpoR to the cell surface have to be regulated. We will study how TpoR dynamics is regulated during myeloproliferative neoplasm. READ MORE
Mutant calreticulin driven myeloproliferative neoplasm
Calreticulin (CALR) is an endoplasmic reticulum (ER) chaperone protein that regulates calcium homeostasis in the cell. In 2013, frameshift mutations in CALR were discovered in patients with myeloproliferative neoplasm with essential thrombocythemia or myelofibrosis. The +1 frameshift mutations occur in the C-terminal tail of the protein. This alters the calcium buffering tail of the CALR into a Met-rich and positively charged region. The mutants also lose the KDEL retrieval sequence that is essential for retrograde transport of CALR from the Golgi to ER. Recent studies have identified TpoR as the primary means of mutant CALR mediated myeloproliferation. We now know that the mutant CALRs induce aberrant TpoR signaling. However, the effects of its novel C-terminal are yet to be unraveled. READ MORE