Synovial sarcoma (SS) is the second most common soft-tissue tumor in children and adolescents after rhabdomyosarcoma. The first case of a fetal synovial sarcoma was recently reported. Synovial sarcoma most frequently develops in the soft tissues of the joints, but is also known to appear in other organs such as the kidney. It is an aggressive tumor with a very high five year-mortality rate and for which no curative therapy exists.

The failure of cancer therapy to control tumor growth results from alterations in the pathways that control cell death decisions within tumors. Although the alterations cancer cells develop to gain a survival advantage are diverse, most ultimately lead to the disruption of death signals that should be Òturned onÓ when lethal stress is encountered. A family of Bcl2-homology (or BH) proteins are responsible for responding to these stressors to initiate a death signal when sufficient stress is present.

Medulloblastoma, the most common solid pediatric tumor, arises in the cerebellum.  This brain region controls posture and coordination.  The development of the cerebellum is marked by rapid division of immature neurons, medulloblastoma "cells of origin".  We want to understand how their fast division promotes their conversion from normal young neurons into tumor cells.  We treated immature mouse cerebellum cells with a protein called Sonic Hedgehog (Shh), which causes medulloblastomas.   The Shh caused these cells to make another protein, Yap1.  In many cancers, Yap1 is found at very high l

Ewing's Sarcoma Family of Tumors (ES) are pediatric tumors of the bone and adjacent tissue. The over-all cure rate is 50-60% with significantly worse prognosis for patients who present with metastatic disease. In order to increase the number of patients who survive ES and to lessen the toxicity to those survivors, ES needs new therapy that goes beyond current chemotherapy. The current 'cytotoxic' therapy could be improved if medicines for ES were more precisely targeted to the ES cancer cells since this would spare the normal organs.

T cell acute lymphoblastic leukemia (T-ALL) is a childhood cancer that is treatable in many instances yet has a significant relapse rate that is difficult to cure.  A common cause for T-ALL is mutation of the gene, Notch, which regulates differentiation of hematopoietic cells, promotes cell survival, and stimulates cellular metabolism of glucose.  The ability of Notch to promote glucose metabolism is shared with many cancers and it has been long appreciated that cancer cells often have increased metabolism compared to their normal counterparts.  Importantly, this aspect of cancer biology ma