The multidisciplinary research program in the lab is led by Sharon Diskin, PhD, who has a broad background in both genomics and computational biology. Research in the lab combines integrative computational analyses of large-scale data such as next generation DNA/RNA sequencing, single nucleotide polymorphism (SNP) genotyping, epigenetic profiling, 3D chromatin looping, and mass spectrometry, with rigorous experimental validation. The overarching goal is to improve patient outcomes.
- Identification of genetic risk factors and their biological relevance in neuroblastoma. The lab identified the first germline copy number variant associated with neuroblastoma. It also helped establish the genetic basis of sporadic NB and demonstrated that genes targeted by NB-associated germline variants not only influence tumor initiation by promoting malignant transformation, but are also required for maintenance of the malignant phenotype.
- Defining the role of structural variation (SV) in neuroblastoma tumorigenesis. The lab identified a rare ~550 kb germline deletion on chromosome 16 associated with neuroblastoma. In parallel, it found that somatic SV breakpoints are enriched in genes involved in neurodevelopment, and identified a novel tumor suppressor, SHANK2, disrupted by SVs in neuroblastoma.
- Identification of optimal immunotherapeutic drug targets for neuroblastoma. The Diskin lab developed an integrative multi-omic approach that combines cell surface mass spectrometry with RNA, DNA, and chromatin immunoprecipitation (ChIP) sequencing from neuroblastoma and a large set of normal pediatric and adult tissues. The lab prioritized several proteins as candidate immunotherapeutic targets that are undergoing validation and functional studies. Downstream pre-clinical work is being performed through collaborative efforts.
- Development of new computational methods for cancer genomics and proteomics. The lab often collaborates on novel computational methods, including CODEX, a method to improve normalization and DNA copy number detection from exome sequencing data, and GiaPronto, a web-based analytical tool for mass spectrometry data used worldwide.
Dr. Diskin's research is focused on translational genomics in childhood cancers. Her laboratory seeks to identify the genetic basis of childhood cancers by combining quantitative computational methods with rigorous "wet-lab" experimental approaches. In parallel, she has developed, and is applying, a proteogenomic approach to identify novel immunotherapeutic targets for high-risk and relapsed pediatric malignancies.