My primary area of clinical activity and research focus is the myelodysplastic syndromes (MDS) and related conditions. This research activity includes development of new therapies, as well as discovery of new somatic genetic mutations important in the pathobiology of this difficult and poorly-understood group of smoldering myeloid neoplasms.
Although there are (as of 2011) currently three FDA-approved therapies for MDS - azacitidine, decitabine, and lenalidomide - only a minority of patients receive substantial benefit from these drugs, and new approaches are needed. I am interested in exploring novel drugs and drug combinations to try to improve patient outcomes.
In addition, because rationally designed therapies are difficult to come by when our collective understanding of disease mechanisms is limited, I am also involved in collaborations with several laboratory-based scientists, particularly Drs. Benjamin Ebert and Mark Fleming, to try to discover new pathways disturbed in MDS and related disorders, with the goal of finding pathways that can be exploited therapeutically. Such collaborations in the past led to the discovery of IER3 translocations or amplification in patients with MDS and chromosome 6p rearrangements, aberrant pre-mRNA splicing as a common MDS-associated phenomenon, and mutations in the ATRX chromatin remodeling factor underlying acquired globin synthesis disorders arising in the context of MDS.