RESEARCH PROGRAM
The THEC laboratory focuses on chemogenomics and cancer biology, with a particular emphasis on hematologic malignancies. Our research is highly translational and conducted in close collaboration with the Hematology Unit of the University Hospital of Parma (A.O.U. Parma).
We integrate small molecule screening with complementary genetic (sh/sgRNA, CRISPR/Cas9), cellular, and genomic (RNA-seq, ChIP-seq, NGS) approaches to identify novel therapeutic targets and strategies. Promising candidates undergo in vivo validation using murine models.
A major research area centers on the Notch1 signaling pathway—a transcription factor frequently mutated in T-cell acute lymphoblastic leukemia (T-ALL)—with the aim of developing new targeted therapies. We have recently characterized CAD204520, a SERCA inhibitor that modulates the Notch1 pathway indirectly. Unlike other SERCA inhibitors, CAD204520 demonstrates reduced off-target toxicity while maintaining potent anti-leukemic activity in vitro and in mouse models.
THEC also investigates the role of Notch1 signaling in other hematologic cancers, including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), as well as additional transcription factors implicated in these malignancies. Although transcription factors represent ideal targets for molecular therapy, they have historically been underexplored in drug development—partly due to the lack of robust high-throughput screening assays and the chemical intractability of these proteins.
To overcome these challenges, we employ diverse small-molecule libraries to identify novel modulators and therapeutic strategies. In this context, the laboratory plays a central role in both national and regional initiatives focused on drug profiling platforms. These efforts aim to integrate compound sensitivity data with genomic profiles to uncover new, personalized treatment options.
THEC LAB 