Research

Overview

We have published paradigm-shifting work on the evolutionary forces driving the emergence of aggressive subpopulations in solid tumors. Using cutting-edge functional genomic platforms (CRISPR in vivo engineering, genetically engineered mouse models and lineage tracing systems), we have discovered that the ‘phenotype’ of cancer cells may direct them to specific evolutionary routes (Perelli et al. Nature 2025). We engage in international collaborations to understand specific vulnerabilities of metastasis and how cells disseminated through the body display ‘metabolic flexibility’ to adapt to new environments (Bezwada, Perelli et al. Nature 2024, Perelli et al. Nature Cancer 2023). Finally, we seek to discover the molecular mechanisms at the basis of malignant transformation, asking:

1. Are mutations in normal cells sufficient for cancer initiation?
2. What is the role of epigenetic remodeling during evolutionary bottlenecks in cancer progression?
3. How do metabolites drive clonal selection in cancer?

Research projects

Metabolic drivers in renal cancer
We have developed sophisticated genetic systems to trace and perturb early pre-neoplastic events in renal cancer tumorigenesis. We are currently studying which changes in metabolite abundance select for pre-malignant cells being able to initiate renal cancer. This transformative work will set the foundations to develop screening strategies to intercept this tumor type.

Tumor maintenance and stemness in glioblastoma
Glioblastoma is a highly aggressive disease that always recurs after therapy. We are investigating a compartment of cancer cells with stemness properties that can sustain tumor growth after therapy. We seek to find what the molecular dependencies of these cells are and to use the knowledge to develop new therapeutic strategies to treat glioblastoma.

Activation of embryological programs in pediatric tumors
Cancer cells are able to activate functional programs that are normally observed during embryogenesis. We are interested in what evolutionary forces act on chromatin remodeling that permit the activation of these programs. This project will transform our knowledge of cell-state-specific activation of embryological programs and how mutations affect cancer and developmental processes.