In this episode of the Epigenetics Podcast, we talked with Francesco Boccalatte from the Genomic Architecture of Cancer lab at the Candiolo Cancer Institute in Turin about his work on chromatin architecture and gene regulation in T-cell leukemia.During his PhD, Boccalatte studied lentiviral gene therapy, stem cells, and microRNAs. He later joined the NYU lab of Iannis Aifantis, where he worked on stem-cell regulation and leukemia. Collaborations with computational scientists led him to study how chromatin structure relates to gene expression and leukemia cell identity, including through genome-wide Hi-C analyses.He explains how the team combined chromatin and gene-expression data, CRISPR experiments, computational predictions, and accessibility data to prioritize regulatory regions and transcription factors for further study. The work identified MIB as a factor that helps maintain certain chromatin structures; inhibiting it disrupted those structures and harmed cancer cells.Boccalatte’s lab now investigates why some patients with T-cell acute lymphoblastic leukemia do not respond to treatment or relapse early despite similar diagnoses and genetic profiles. The team is studying patient epigenomes and using machine learning to improve patient stratification and identify potential treatment directions. He closes by advising early-career scientists to stay curious, seek innovative approaches, and follow the questions that sustain their interest.ReferencesWang Q, Boccalatte F, Xu J, Gambi G, Nadorp B, Akter F, Mullin C, Melnick AF, Choe E, McCarter AC, Jerome NA, Chen S, Lin K, Khan S, Kodgule R, Sussman JH, Pölönen P, Rodriguez-Hernaez J, Narang S, Avrampou K, King B, Tsirigos A, Ryan RJH, Mullighan CG, Teachey DT, Tan K, Aifantis I, Chiang MY. Native stem cell transcriptional circuits define cardinal features of high-risk leukemia. J Exp Med. 2025 Apr 7;222(4):e20231349. doi: 10.1084/jem.20231349. Epub 2025 Feb 19. PMID: 39969525; PMCID: PMC11837855.Gambi G, Boccalatte F, Rodriguez Hernaez J, Lin Z, Nadorp B, Polyzos A, Tan J, Avrampou K, Inghirami G, Kentsis A, Apostolou E, Aifantis I, Tsirigos A. 3D chromatin hubs as regulatory units of identity and survival in human acute leukemia. Mol Cell. 2025 Jan 2;85(1):42-60.e7. doi: 10.1016/j.molcel.2024.11.040. Epub 2024 Dec 23. PMID: 39719705; PMCID: PMC11934262.Related EpisodesEpigenetic Regulation and Small Molecule Innovation in AML: Advances in Translational Leukemia Research (Ani Deshpande)MLL Proteins in Mixed-Lineage Leukemia (Yali Dou)Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)ContactEpigenetics Podcast on MastodonEpigenetics Podcast on BlueskyDr. Stefan Dillinger on LinkedInActive Motif on LinkedInActive Motif on BlueskyEmail: [email protected]