June 2023 – Monthly portrait of a young researcher

Alessio Locallo

Alessio Locallo is a Ph.D. student enrolled by The International Doctoral Program in Molecular Mechanisms of Disease (iMED) at the University of Copenhagen. His research interests include using brain cancer biology, bioinformatics and statistics to understand the clonal evolution of brain tumor samples in human patients by combining multiple approaches and data sources.

Alessio Locallo is currently working in Prof. Joachim Weischenfeldt’s group at the Biotech Research & Innovation Centre and Finsenlab, Copenhagen University. He is working on the Molecular characterization and identification of clonal evolution of brain tumors (WP1).

Glioblastoma (GBM) is the most frequent malignant primary brain cancer in adults and it often rapidly recurs after initial therapy. As for most of the tumors, it typically evolves as a heterogeneous mixture of genetic clones and subclones and this could potentially contribute to treatment failures. The underlying evolutionary processes remain poorly understood. Therefore, Alessio’s aim to disentangle the relationship between tumor growth and genetic evolution is of crucial importance, as the identification of the chronology of molecular alterations may identify milestones in carcinogenesis.

Using Whole Genome Sequencing (WGS) data from paired tumor material from primary and at least one relapse from human patients, Alessio reconstructs the tumor phylogeny using principles from evolution and phylogeny, by comparing the molecular alterations in the primary tumor to the matched sample at relapse, in order to identify clonal changes that have persisted treatment to cause relapse.

Additionally, he develops and implement novel methodologies to infer the clonality of 3D chromatin conformation changes in tumor cells using Hi-C data, a peculiar topic that hasn’t been extensively addressed so far.

In all, Alessio’s reasearch, integrating mutations and chromatin interactions from WGS and Hi-C to reconstruct the clonal evolution and to identify recurrent clinical trajectories, will increase the ability to better understand how a tumor evolves over time, in order to correctly address the therapeutic approaches in the context of precision medicine.

Poster:

Tracing clonal evolution in brain tumors following treatment

Research focus:

• Genome-wide profiling of cancer related alterations
• Tumour phylogeny reconstruction and analysis

WP relation:

WP1 – Molecular characterization and identification of clonal evolution

Associated researchers / supervisors:

Prof.Joachim Weischenfeldt (supervisor)