Jack F. Shern, M.D.
Dr. Jack Shern is a physician scientist within the Pediatric Oncology Branch. His research is focused on defining and developing precision therapies targeting the genetic mutations that drive tumorigenesis. Most recently, his efforts have turned towards using single cell sequencing to discover tumor subclonal populations that are responsible for relapse and refractory disease. He is actively engaged in the Children's Oncology Group, working on pediatric soft tissue sarcomas to investigate the utility of using mutational information as biomarkers for the diagnosis and management of pediatric rhabdomyosarcoma.
1) rhabdomyosarcoma, 2) fusion oncogenes, 3) precision medicine, 4) whole genome
sequencing, 5) RNA sequencing, 6) epigenetics
1. Detect and define the somatic lesions that drive tumorigenesis of rare and deadly pediatric tumors. In particular, we are interested in translocation events that produce fusion oncogenes of transcription factors. These events are the driving lesions in many of the difficult to treat pediatric sarcomas such as alveolar rhabdomyosarcoma and Ewing sarcoma. Interestingly, we have found that while these fusion oncogenes are often one of the few genetic rearrangements observed in within these tumors, they have profound effects on the transcriptional output of these cells.
2. Resolve underlying tumor heterogeneity and mechanisms of resistance that allow a tumor to progress or relapse after therapy. To accomplish this, we are using and developing novel droplet based methods to barcode and sequence and analyze the expression profile from thousands of cells in a single experiment.
3. Use high-throughput siRNA, small molecule and natural product drug screening to discover precision therapeutics designed to target a tumors underlying genetic or epigenetic drivers. The results of these studies are being rapidly translated into potential clinical trials within the Pediatric Oncology Branch.
Selected Key Publications
4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors.Nature Med.. 21: 581-590, 2015. [ Journal Article ]
- PLoS Genet.. 11(3): e1005075, 2015. [ Journal Article ]
- PLoS Genet.. 10(7): e1004475, 2014. [ Journal Article ]
Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of alterations affecting a common genetic axis in fusion-positive and fusion-negative tumors.Cancer Discovery. 4: 216-231, 2014. [ Journal Article ]
- Critical Rev in Oncogenesis. 20: 227-243, 2015. [ Journal Article ]
|Thomas Fountaine M.D.||Clinical Fellow|
|Ira Kraft||Special Volunteer|
|Haiyan Lei Ph.D.||Bioinformatics Specialist (Contr.)|
|Carly Sayers Ph.D.||Postdoctoral Fellow (CRTA)|
|Xiyuan Zhang Ph.D.||Postdoctoral Fellow (Visiting)|