Luigi A. G. Laghi

M.D., PhD. is Associate professor of Gastroenterology at the University of Parma since April 2020. He owns specialties in Internal Medicine and Gastroenterology, and PhD in gastrointestinal oncology. Academically, Dr. Laghi has been acknowledged by the Italian Minister for University and Research as full professor of gastroenterology in January 2020. He accomplished his fellowships at University of Ann Arbor (MI), directed by Tadakata Yamada, then at University of California San Diego, with Richard Boland. As clinician-scientist he built his CV on biomarkers aimed at improving colorectal cancer (CRC) progression and management. As pivotal experience in Italy, he started and run the Hereditary Cancer Genetics Clinic of the Humanitas Clinical and Research Center, for gastrointestinal tumors. As secretary of the Colorectal Cancer Working Group of Alliance Against Cancer (ACC) funded by the MoH, he recently contributed to launch next generation sequencing programs in the IRCCS foundation, participating to the design of the incoming national program, and currently he is acting as member of the Gersom project steering committee and of the related tumor molecular board. As translational clinician-scientist, Dr. Laghi initially worked on the detection of the polyoma virus JC (JCV) in CRC tissues under the mentorship of Prof. V Neel and Prof. CR Boland, at UM and UCSD. He found T antigen DNA sequences of JCV in the mucosa of normal human colons, CRCs, and CRC xenografts raised in nude mice, and in the human colon cancer cells. He demonstrated that the negatively supercoiled JCV, in the human tissues, can be easily detected by the treatment with topoisomerase I. His results indicate that JCV DNA can be found in colonic tissues, which raises the possibility that this virus may play a role in the chromosomal instability observed in colorectal carcinogenesis. While working with Prof. Boland, Dr. Laghi did not neglect the molecular basis of inherited CRC, with emphasis on Hereditary Non-Polyposis Colorectal Cancer in the setting of deficient DNA mismatch repair (or Lynch syndrome). Dr. Laghi collected one of the largest mono-institutional series of CRC in Europe, addressing inherited CRC and the underlying types of genomic instability, chiefly mismatch repair defects. Dr. Laghi focused his scientific work in the field of Microsatellite Instability (MSI), demonstrating that MSI is a stage-dependent predictor of survival in patients with colorectal cancer and that the decreased likelihood of metastases in patients with MSI cancer is associated with specific genetic and epigenetic changes of the primary tumor. Thereafter, he included in his translational studies the density of tumor infiltrating immune cells as non-clonal determinants of patient prognosis. He found that metachronous metastases are unlikely to arise from node-negative (i.e., stage II) CRCs with a high-density CD3+ tumour-infiltrating lymphocytes (TILs), whereas high densities of CD3+ TILs are not associated with the absence of postsurgical metastasis in patients with node-positive colorectal cancer (stage III). These data suggest that densities of CD3+ TILs cannot be used as an independent predictor of clinical outcome in patients with stage III colorectal cancer and, at least for now, the tumor-node-metastasis classification should remain the preferred prognostic system. These findings are consistent with a relationship between nodal involvement and tumor immune-evasion. He replicated these findings in other independent papers concerning other immune-cell populations (published and unpublished results). Currently, new interesting results in this field concern the identification of immune populations of macrophages the density of which can predict the responsiveness to chemotherapy. In parallel, looking for innovative CRC biomarkers in the peritumoral stroma, led Dr. Laghi to test this heterogeneous milieu for the presence of non-canonical neoplastic cells possibly exploiting epithelial-to-mesenchymal transition (EMT) to invade the nearby tissues. His team first demonstrated that the peritumoral stroma of CRC harbors tumor cells in mesenchymal disguise, sharing the same genetic abnormalities of cancer cells. Moving from this finding, his group also showed that EMT factors can be detected in the blood of CRC patients and is actively working on this issue as a diagnostic and possibly prognostic tool in CRC and pancreatic cancer (Patent. European Patent Office, Application No. 13197367.9-1403). As a clinician, he has both degrees in Internal Medicine and Gastroenterology, and has taken care of out-patients as well as of in-patients for more than 20 years, being actively involved in the management of clinical cases at the Humanitas Research Hospital. Besides varying clinical duties, he run practice dedicated to the recognition of inherited predisposition to gastrointestinal cancers and to the risk management of developing colorectal and pancreas cancer. He transferred this expertise in the Emilia district, starting a similar program within the AOU of Parma. He serves as a reviewer for major international journals, spanning clinical and translational research, such as Gastroenterology, Gut, Cancer Research, Clinical Cancer Research, Cancer Immunology Research. Summary of publication records (source, Scopus): Hirsch (H) index, 38. Papers, 111. Overall citation, 7858. Total IF > 600.