Professor Guido Franzoso M.D., Ph.D. is Head of the Centre for Cell Signalling and Inflammation and Professor and Chair of Signal Transduction and Inflammation at Imperial College London. He holds an honorary consultant position at Imperial College Healthcare NHS Trust.
Professor Franzoso joined Imperial College London in 2007, having previously been a member of Faculty at The University of Chicago for ten years. Prior to this, he was a Visiting Associate at the National Institutes of Health, Bethesda, Maryland, and a staff physician at the University-Hospital of Padua. Professor Franzoso holds a medical degree from the University of Padua, Italy, and a Ph.D. in microbiological sciences from the Institute of Microbiology at the University of Padua.
Professor Franzoso’s research in the areas of gene transcription and signal transduction focuses on the regulation and function of NF-κB transcription factors in inflammation and oncogenesis, and the development of better strategies for therapeutically targeting the NF-κB pathway in human disease. NF-κB signalling is aberrantly activated in the large majority of human cancers, where it drives oncogenesis, disease recurrence and therapy resistance by upregulating survival genes and other tumour-promoting mechanisms. However, despite a global search of 30 years, no specific NF-κB inhibitor has been clinically approved, due to the preclusive toxicities associated systemic NF-κB inhibition.
In 2001, Professor Franzoso’s laboratory discovered that NF-κB inhibits apoptosis by suppressing the JNK MAPK cascade via its transcriptional target, GADD45β1,2, which blocks the JNK kinase, MKK73. His team subsequently identified the GADD45β/MKK7 complex as an essential, cancer cell-restricted survival module dependent on aberrant NF-κB signalling in multiple myeloma4, an incurable malignancy of plasma cells. These discoveries paved the way to the development by his laboratory of the conceptually novel NF-κB-targeting therapeutic, DTP3, which disrupts the GADD45β/MKK7 interaction by binding to MKK7 and, as a result, selectively kills multiple myeloma cells without toxicity to normal tissues4. Professor Franzoso’s research in this area demonstrated that cancer-selective inhibition of the NF-κB pathway is possible and promises profound benefit to patients with multiple myeloma and, potentially, other cancers in further areas of unmet need. With support endowed by the MRC, Professor Franzoso’s team is conducting a Phase I/IIa study of DTP3 in patients with multiple myeloma to achieve proof-of-concept for a cancer-selective NF-κB-targeting strategy as a safe and effective means to treat cancer patients.
Further interests of Professor Franzoso’s laboratory include investigations into the functions of NF-κB in energy metabolism and inflammation as a way to understand mechanisms of pathogenesis in cancer as well as inflammatory and metabolic diseases and ultimately identify innovative NF-κB-targeting strategies to improve the treatment of malignant and non-malignant human pathologies5.
Professor Franzoso’s basic and clinical research is supported by substantial funding from various organisations, including the MRC, Cancer Research UK, Bloodwise and the NIH. Professor Franzoso is an inventor on several patents on IP related to his research.
et al., 2020, NF-κB and mitochondria cross paths in cancer: mitochondrial metabolism and beyond, Seminars in Cell and Developmental Biology, Vol:98, ISSN:1084-9521, Pages:118-128
et al., 2019, Clinical proof of concept for a safe and effective NF-κB-targeting strategy in multiple myeloma, British Journal of Haematology, Vol:185, ISSN:1365-2141, Pages:588-592
et al., 2019, Preclinical toxicology and safety pharmacology of the first-in-class GADD45β/MKK7 inhibitor and clinical candidate, DTP3, Toxicology Reports, Vol:6, ISSN:2214-7500, Pages:369-379
et al., 2018, Probing the interaction interface of the GADD45 beta/MKK7 and MKK7/DTP3 complexes by chemical cross-linking mass spectrometry, International Journal of Biological Macromolecules, Vol:114, ISSN:0141-8130, Pages:114-123
et al., 2018, Turning an old GADDget into a troublemaker, Cell Death and Differentiation, Vol:25, ISSN:1350-9047, Pages:640-642