Riaz Gillani, M.D. – 2026

Neuroblastoma (NBL) is the most common solid tumor impacting children, with 50% of high-risk patients relapsing despite intensive treatment. We and others have found that inherited risk factors, as well as features of how tumor DNA is rearranged and organized, contribute to the development and aggressiveness of NBL. However, the full extent of how these different aspects of biology in the normal and tumor tissues connect is unknown, and a better understanding of this unified biology has the potential to improve treatment in NBL. 

In this proposal we will analyze the normal and tumor tissues from NBL patients to gain new insight into how tumor DNA breaks and reorganizes itself so that we can use this information to A) identify and track disease that is likely to relapse and B) develop new treatment strategies that target this biology. In the first aim of our proposal, we will focus on understanding DNA breakage in neuroblastoma. We will analyze the whole-genome sequencing (WGS) of the normal tissues of close to ~1,000 patients with NBL, as well as individuals who do not have NBL, to identify mutations that impact DNA breakage and repair. We will relate these mutations to patterns of DNA breakage in patient tumors and in cell line models. In the second aim of our proposal, we will focus on DNA reorganization in NBL. We will again analyze WGS from the normal tissue of NBL patients and unaffected individuals, and this time look for mutations across the genome (inside and outside of genes) that can impact how DNA is organized. We will relate these findings in the normal tissues to different patterns of DNA organization and gene expression in NBL tumors and use this to identify specific gene expression patterns that can be “reprogrammed” as a treatment strategy in cell line models.