Cancer

Numerous research groups in Trieste, in Cape Town, and in New Delhi investigate the genetic and molecular mechanisms of cancer development. In Cape Town, the Cancer Genomics Group (Zerbini) develops novel therapeutics targeting various cellular proteins that are deregulated in cancer. The Protein Networks Group in Trieste (Myers) uses high-throughput mass spectrometry to perform proteomics studies to understand how protein complexes regulate normal and cancer cell behaviour, particularly in the process of protein modification. The Molecular Hematology Group in Trieste (Efremov) is interested in deciphering the intracellular signaling pathways that control the proliferation, differentiation and survival of normal and malignant B-lymphocytes. The Membrane Protein Biology Group in Delhi (Arulandu) investigates the molecular mechanisms underlying the function of membrane proteins, focusing on chloride intracellular channels as potential novel anti-cancer targets. The Tumour Virology Group in Trieste (Banks) studies the mechanisms by which Human Papillomaviruses (HPVs) infect cells and cause cervical cancer.

Highlights 

The Hematology Group in Trieste revealed a novel mechanism of action of a cytotoxic agent that had previously been proposed to function as a BCL-2 antagonist. This drug was shown to selectively kill chronic lymphocytic leukemia (CLL) and diffuse large B cell lymphoma cells by inhibiting the PI3K/AKT pathway and downregulating MCL-1 (Cell Death Dis. 2020). In addition, the Hematology Group developed a novel CRISPR/Cas9-based approach that allows for rapid and simultaneous introduction of multiple human CLL-specific genetic lesions into primary murine B cells. This approach was used to generate murine leukemias with the genetic make-up of human CLL and discover novel drug combinations for personalized treatment of CLL (Blood, revised manuscript submitted). The Tumour Virology Laboratory made advances in the understanding of the molecular mechanisms increased oncogenicity behind the higher risk Human Papillomavirus HPV58 V1 variant (J Virol 94:e00090-20, 2020).