Basic cancer research in Pediatric Hematology and Oncology has been directed at increasing our understanding of the molecular biology of both normal and malignant cellular growth and regulation. Our investigators have made important observations using mouse transgenic models, mammalian cell culture approaches, and C. elegans. In C.elegans the focus has been on erm-1. Erm-1 is the the C.elegans ortholog of the ezrin-radixin-moesin family of submembraneous linkers, which also contains the neurofibromatosis 2 tumor suppressor. These molecules have a role in cell shape morphogenesis and growth regulation. In addition, we have described a novel knockout technique in C.elegans using gene conversion. This technique can be further modified for use in other invertebrate and vertebrate systems.

Another group of investigations are focusing on identifying tumor suppressor genes and cooperating mutations in acute myeloid leukemia. These studies have recently identified two genes, TLE1 and TLE4, members of the Groucho family of co-represssors, that appear to have features of tumor suppressor activity and may cooperate with AML1-ETO in leukemogenesis.

We have also had a longstanding interest in determining the functions of c-myc in growth control. Recent studies are characterizing transcriptional control of a basal element in the eIF4E promoter to better understand the contextual functions of c-myc.  

 In the area of hematology we have had a continued focus on defining the role of tissue factor and it's relation to endothelial cells and the rheology of flowing blood and interactions with vessel  walls. In collaboration with the Pediatric Renal group at MassGeneral Hospital for Children our investigators have been studying the role of tissue factor in childhood HUS (hemolytic-uremic syndrome).

Investigators:
Emmett V. Schmidt, MD, PhD
David A. Sweetser, MD, PhD