Dr. Wells' research program is focused on hematopoiesis, which is the process by which blood cells develop in the bone marrow, and how this process goes wrong in the diseases myelodysplastic syndrome and acute leukemia. By identifying distinguishing characteristics of myelodysplastic and leukemic stem cells, Dr. Wells' team hopes to develop new targets for therapy that will permit more effective and less toxic treatments for these diseases.
A central paradox in MDS biology is how the myelodysplastic stem cell out-competes normal stem cells and comes to dominate the bone marrow. We hypothesized that the competitive advantage enjoyed by the MDS stem cell consists in an enhanced capacity for self-renewal, and identified gene that mediate this property in leukaemia cells. One of the genes we identified, EAR- 2, is also more highly expressed in MDS and leukaemia than in normal bone marrow. We have found that EAR-2 expression blocks differentiation of leukaemia cells in culture and leads to the development of leukaemia when overexpressed in mouse bone marrow. We are now studying the mechanism by which EAR-2 alters stem cell behaviour, and its role in the multistep pathogenesis of MDS and AML.
