We are part of a collaborative effort at UCSF to study the biology of pediatric sarcomas and other pediatric cancers using genomic approaches.

The two specific sarcomas we have focused most of our attention on are: 

Ewing Sarcoma

Chromosomal translocations are frequent genetic events in the genesis of many human cancersandare particularly frequent in in pediatric cancers. In Ewing's sarcoma, the most common translocation is EWS/FLI-1. Our laboratory was the first to describe a role for lncRNAs in this disease (Marques et al JCI, 2013). We continue to have a strong interest in lncRNA biology as it pertains to Ewing pathogenesis and have an R01-funded research program in this area. We have developed a well-characterized collection of Ewing sarcoma PDXmodels, most of which have been analyzed by RNAseq and WGS and functionally characterized with regards to their metastatic capacity. A wide range ofpossible research opportunities in Ewing sarcoma biology are available for graduate student and post-doctoral trainees.

Osteosarcoma 

Our laboratory has a strong interest in Osteosarcoma, another bone cancer, that is most commonly seen in adolescents and young adults. A key problem for advancing Osteosarcoma research is that this is a rare disease and primary tumor samples from patients are difficult to obtain. Wehave established a large (over 30 to date) bank of primary xenograft samples from both pre and post-chemotherapy patient samplesfrom Osteosarcoma patients. We have also generated a panel of cell lines from these PDX models. Extensive RNAseq and WGS analysis of both PDX and matched cell lines is available. This is a rich resource for translational studies to understand the molecular underpinnings of Osteosarcoma development, chemoresistance and metastasis. We haveusedthese PDX models and matching tumors to identify potential targeted therapies for subsets of osteosarcoma patients (Sayles and Breese et al, Cancer Discovery 2019). This work has had significant impact in the field as previously it was not widely appreciated that osteosarcomas could be vulnerable to targeted therapies directs at highly amplified (but not mutated) cancer genes such as MYC, CDK4 and others. We are especially interested in using PDX models and genetically engineered models of osteosarcoma to study metastasis.