Luigi Laghi MD, PhD. Chief of Laboratory of Molecular Gastroenterology and GI Consultant - Dept. of Gastroenterology View More
Dr. Laghi’s team takes advantages/uses of translational studies, based on large series of patients, to investigate Colorectal and Pancreatic Cancers. Four main research fields – i.e, molecular bases of hereditary GI Cancers, relationships between tumor and immune system, relevance of EMT, genetic variants and aggressiveness of pancreatic cancer- are pursued for the clarification of prognostic and predictive markers of CRC and PC, and of molecular mechanisms implicated in tumor progression and metastasis.
Genomic instability and mismatch repair defects
Microsatellite Instability to act as stage-dependent predictor of survival in Colorectal Cancer patients alongside a decreased risk of metastases, due to specific genetic and epigenetic changes of the primary tumor. Focusing on the molecular basis of Hereditary Non-Polyposis Colorectal Cancer in the setting of deficient DNA mismatch repair (or Lynch syndrome), a large mono-institutional series of Colorectal Cancer was collected to address the prognostic role of underlying types of genomic instability.
Tumor infiltrating immune cells
Colorectal cancer relies on the TNM classification system to prognosticate the outcome of the disease, yet the information provided from TNM staging is incomplete, and there is a strong need for better biomarkers. Recently, translational studies on the density of tumor infiltrating immune cells pointed to the crucial role of the immune response against CRC progression. The lab is interested in the characterization of components of the innate and adaptive immune systems as prognostic and predictive biomarkers.
The heterogeneous milieu in the peri-tumoral stroma may harbor non-canonical neoplastic cells likely to exploit EMT to become able to invade nearby tissues and blood vessels, to eventually contribute to metastasis. We first observed peri-tumoral stroma of CRC harboring mesenchymal cells with the same genetic abnormalities of cancers cell, and then we detected specific EMT factors in the blood of patients. The lab is assessing the possibility to employ a “liquid-biopsy” test, exploiting such increased levels, for an innovative diagnostic approach to the diagnosis of PC and CRC (European Patent, No. 13197367.9).
Role of genetic variants on aggressiveness of pancreatic cancer
Despite the recent advances in understanding the genome landscape of PC, this disease remains one of the most lethal with few therapeutic treatment options. Our data highlight the association of H63D polymorphism with increased risk of surgically resectable pancreatic cancer, and its critical role in the increased aggressiveness of PC. Nevertheless, the underlying mechanisms are still unclear. Our research is aimed to clarify the contribution of genetic HFE variants in modifying background host immune response and favoring pancreatic cancer progression.
Luigi Laghi Publications
Cavalleri T, Bianchi P, Basso G, Celesti G, Grizzi F, Bossi P, Greco L, Pitrone C, Valtorta E, Mauri G, Truini M, Dall'Olio FG, Brandi G, Sartore-Bianchi A, Ricciardiello L, ...