Patients suffering from or having suffered from chronic hepatitis C are more likely to develop liver cancer. At the Institute for Research on Viral and Liver Diseases, Joachim Lupberger is interested in the still unknown mechanisms responsible for this greater susceptibility. Research supported by IdEx Attractivité funding since 2014.
Chronic infection with hepatitis C virus (HCV) is far from trivial. It causes lasting damage in the liver of patients, who, even when cured, present an increased risk of developing cancer in this organ. To better understand this harmful link, Joachim Lupberger, a German researcher with an atypical career path (see box), tries to characterise the intra-cellular signalling pathways destabilised by HCV. In his sights: phosphatases, regulatory enzymes whose dysfunction is at the origin of many human diseases. Joachim Lupberger studied the expression of 86 known phosphatases in liver biopsies of patients with chronic hepatitis C. 'I observed that the expression of 29 of them were significantly disrupted in these patients. Among the enzymes affected are so-called 'tumour suppressor' phosphatases which, by inactivating signals that promote cell proliferation, prevent the development of cancers.
A welcome scholarship
On the basis of these results, Joachim Lupberger received IdEx Attractivité funding in 2014 to plunge further into his research. Thanks to the 100,000 euros of the scholarship, he recruited a technician who was 100% involved in the project and rehabilitated a laboratory that was no longer used by the research unit. A real boost that allowed him to validate his hypotheses on about thirty additional biopsies and to study the role of a particular phosphatase called PTPRD. 'I have demonstrated that this enzyme was virtually no longer produced in infected liver cells and in tumour lesions. However, it inactivates a proliferative signal known as STAT3 with a well-known carcinogenicity. In previous studies, the researcher has shown that activation of this oncogene is essential for HCV to infect the liver cells. 'Our study suggests that HCV blocks the expression of phosphatase PTPRD so as to overactivate and take advantage of the STAT3 signal,' says the researcher. In doing so, the virus paves the way for uncontrolled cell proliferation. Consequence: Patients undergoing this effect have a lower life expectancy.
As an extension of the project, Joachim Lupberger intends to prove that the virus permanently suppresses the expression of PTPRD even after its eradication from the organism. The researcher suspects that there is a persistent 'epigenetic footprint' in patients with chronic hepatitis. In other words, an indelible mark left, not in the genetic code in the manner of a mutation, but on the surface of the DNA. 'If we prove its existence, it would be a major step forward! »