Research in the Nagarajan laboratory focuses on two major areas: deletions and translocations of chromosome 5q and the SMAD5 pathway in hematopoiesis and leukemia. Anomalies of chromosome 5q are associated with poor prognosis in leukemia patients, suggesting that loss of regulatory genes from these loci facilitate malignant transformation. Recent work in our laboratory resulted in the isolation of a novel regulatory gene, SSDP2, that is disrupted in human leukemia. Current studies focus on understanding the functional consequence of this disruption. The SMAD5 gene, a transcriptional coactivator that transduces signals from the BMP family of peptides mediates commitment to hematopoietic differentiation in lower organisms. However, very little is known about this pathway in humans. We are interested in identifying target genes that are regulated by SMAD5 and determining how they in turn give rise to the multiple differentiated cell types found in human blood.