Childhood Cancer Research
University of Texas Health Science Center at San Antonio
San Antonio, TX 78229
United States
Ewing sarcoma is an aggressive cancer that primarily affects children and adolescents. There are no targeted therapies for Ewing sarcoma and the prognosis upon relapse or metastasis is bleak for most patients. The major vulnerability of Ewing sarcoma, the fusion protein EWS::FLI1, has proven to be undruggable despite heroic efforts by many research groups. We are proposing an entirely novel approach that will uncover new, high-resolution structural insights about behavior and properties of the EWS::FLI1 fusion.
Current therapies for children with rhabdomyosarcoma are highly toxic and cause lifelong complications for survivors. In addition, high-risk patients have very poor outcomes. More effective and less toxic therapies are needed for these patients. Fusion-negative rhabdomyosarcoma is the more common rhabdomyosarcoma, characterized by frequent cancer-causing mutations in genes called the Ras family genes. We and others have shown that interventions targeting a signaling pathway called the Mitogen Activated Protein Kinase pathway would benefit patients with fusion-negative rhabdomyosarcoma.
Background
Epigenetic changes, including methylation, are reversible chemical modifications that can affect gene expression. DNA, histones (the proteins that package the DNA) and RNA are subject to such modifications. Aberrant DNA and histone methylation have been clearly linked to cancer, however, the impact of RNA methylation in cancers is poorly understood.
Cancers of neural and neuroectodermal origin are rare in incidence. However, high rates of mortality convert these infrequent tumors into the second leading cause of cancer-related death among children less than 15 years of age. Genetic analysis of familial cancers provides fundamental insights into their more common sporadic equivalents. Using integrative genomics, we recently identified a novel cancer gene known as TMEM127. We discovered that truncating TMEM127mutations are responsible for the development of familial pheochromocytomas, highly vascular tumors of neural crest origin.
Background
My research interest is a cancer called rhabdomyosarcoma, and specifically the alveolar variant. Alveolar rhabdomyosarcoma is an aggressive childhood tumor that is difficult to treat when the disease goes beyond the primary site and is virtually incurable when widely metastatic.
