Anand G. Patel Lab

Our lab investigates the mechanisms of treatment persistence and recurrence in pediatric cancers such as rhabdomyosarcoma. We use patient samples and experimental patient-derived models to investigate tumor evolution during therapy. Using single-cell sequencing and spatial technologies, we developed methods to track and identify the rare malignant cells that persist during therapy. Additionally, we have an interest in understanding how the non-malignant cells of the tumor microenvironment–fibroblasts, immune cells and endothelium– contribute to persistence. Ultimately, our goal is to leverage the molecular mechanisms of tumor persistence to identify exploitable vulnerabilities and develop novel treatment options.

We use a combination of well-established and emerging techniques, including single cell sequencing, spatial transcriptomics, computational biology, patient-derived xenografts, spheroids and 3D-printed tumor models to address our scientific questions. 

Rhabdomyosarcoma can be molecularly classified into two major molecular subtypes: fusion-negative or fusion-positive rhabdomyosarcoma. In fusion-negative rhabdomyosarcoma, we have identified rare cells that mimic early muscle progenitors that survive treatment and rapidly regenerate to propagate tumors. In contrast, we found that fusion-positive rhabdomyosarcoma cells do not have progenitor-like cells, and malignant cells undergo a transition into non-myogenic lineages during therapy. However, the molecular mechanism underlying how each cell population contributes to recurrence remains unclear. We aim to better our understanding of what defines and regulates these tumors cells, thereby enabling them to regenerate tumors after therapy. 

The incorporation of antibodies targeted against the disialoganglioside GD2 (anti-GD2) has dramatically improved outcomes for children diagnosed with high-risk neuroblastoma. These clinical responses demonstrate that the immune system, when harnessed correctly, can be deployed to treat pediatric cancers. By studying the tumor microenvironment, we gain valuable insight into the molecular interplay between immune and malignant cells in treated and untreated tumors. Using this information, we aim to identify biomarkers for response in neuroblastoma and to find analogous immunotherapy targets in other pediatric solid tumors.