Departmental Seminar: Dr. Cayetano Gonzalez (IRB Barcelona)

Departmental Seminar

Speaker: Dr. Cayetano Gonzalez

Institution: IRB Barcelona
Title: Drosophila Models of Pediatric Oncogenic Fusion Genes: Unraveling Mechanisms and Identifying Therapeutic Vulnerabilities

Date: July 21^st, 2025

Time: 3:00 PM 

Host: Dr. Howard Lipshitz

Location: MSB 2170

Abstract:

Oncogenic gene fusions, caused by chromosomal rearrangements, are defining molecular alterations in many pediatric cancers. These fusions lead to unscheduled gene activation or the creation of aberrant in-frame fusion proteins,
which are particularly prevalent in sarcomas, leukemias, and lymphomas. Examples include PAX::FOXO1 in alveolar rhabdomyosarcoma (ARMS), EWS::FLI1 in Ewing sarcoma (EWS), SS18::SSX in synovial sarcoma (SS), AML1::ETO in acute myeloid leukemia (AML), and ETV6::RUNX1 in acute lymphoblastic leukemia (ALL). Remarkably, the molecular functions and biological processes of certain pediatric oncogenic fusion proteins are highly conserved, allowing for their study in Drosophila models: upon heterologous expression, human oncogenic fusions consistently recapitulate key neomorphic transforming activities in Drosophila, as documented for AML1/ETO (PMID: 20688956), PAX::FOXO1 (PMID: 22182840), and EWS::FLI1 (PMID: 36714878). Furthermore, Drosophila models can also leverage evolutionary divergence, as differences in signaling pathways, protein interactions, or cellular contexts between Drosophila and mammalian systems can unveil critical mechanistic insights that might be obscured in evolutionarily closer mammalian models. Thus, Drosophila models of pediatric oncogenic fusion proteins offer a robust and genetically tractable platform for dissecting the mechanistic underpinnings of pediatric oncogenesis and identifying vulnerabilities.