Transcriptomics and Functional Genomics in JMML and B-ALL

Research Activity

The goal of the group is to identify at the genomic, transcriptomic, epigenomic and single-cell multi-omic level the networks of acquired and inherited aberrations that drive the development and the progression of B-cell Acute Lymphoblastic Leukemia (B-ALL) and Juvenile Myelomonocytic Leukemia (JMML). Indeed, the group has a strong expertise in generation, analysis and integration of data supporting the improvement of diagnosis, risk stratification and treatment of leukemia pediatric patients supported by experimental and functional studies using both in vitro and in vivo disease models. The main projects of the group are listed below.

A multimodal integrated single cell strategy to erase Juvenile Myelomonocytic Leukemia.

This project aims to understand the regulatory mechanisms behind JMML by analyzing single-cell transcriptome and epigenome regulation. We will explore the interactions between cancer cells and the bone marrow microenvironment. Using CRISPR/Cas9 genome wide screening, our goal will be to identify new biomarkers and therapeutic targets. The results will also be validated in patient-derived xenograft models to ensure clinical applicability.

Dissecting Juvenile Myelomonocytic Leukemia complexity: 3D epigenomic landscape and AI-powered multi-omics patient stratification.

We plan to investigate JMML patients’ 3D chromatin architecture and leverage Artificial Intelligence (AI) based multi-omics data analysis to integrate clinical, epigenetic, genetic and transcriptome features. We will focus on modeling deeper JMML heterogeneity, discovering new biomarkers and providing a useful tool for clinicians to better classify patients, thus improving therapeutic interventions and clinical outcome.

CircRNAs involved in mechanisms of malignant transformation and relapse in T-ALL: towards new RNA-based therapies

This project aims to disclose new mechanisms of leukemogenesis and resistance in T-ALL focusing on circRNA roles in mechanisms of malignant transformation. CircRNAs are transcripts in which a downstream splice donor site is covalently bound to an upstream acceptor by backsplicing. The discovery of circular RNAs (circRNAs) added a new layer to our understanding of transcriptome complexity. They can act as miRNA sponges, interact with RNA-binding protein or can also be translated into peptides. The project focuses on the study of these circRNA in leukemogenesis mechanisms by in vitro model. This project is in collaboration with Prof. Bortoluzzi Stefania (DMM, University of Padova).

Precision medicine and clonal evolution investigation on high risk B-ALL

In the last decade a great advance in the comprehension of the genetic and biological bases of child-hood leukemia has been achieved and genomic analysis contributed to the improvement of risk stratification and patient treatment, however about 20% of BALL patients present treatment resistance and relapse; our group is involved in the identification of genomic and transcriptomic alterations of high risk BALL patients and in particular of therapy resistant and relapsed patients; we characterize by different omics approaches (exome, RNA-seq, gene expression profiling) driver mutations in BALL patients to identify drug resistance mechanisms and clonal structure and track clonal dynamicity between diagnosis and relapse.

Advanced diagnostics in JMML

We leverage Next Generation Sequencing (NGS) to identify mutations and track their evolution during treatment and follow up, in order to provide clinicians with a precise tool to guide therapeutic interventions.