Supervisor: Dr. Marie-Isabelle Garcia
Our research focuses on understanding the molecular and cellular mechanisms that regulate the gastrointestinal tract in normal conditions and during diseases such as chronic inflammatory bowel disease and cancer. We pay special attention to G protein-coupled receptors (GPCRs), as they are the main targets of most available drugs (website: https://www.iribhm.org/marie-isabelle-garcia).
Project 1-Cancer biology-Organoids
Exploring the role of the stem cell marker LGR6 in colorectal cancer and chemoresistance
Context:
Is targeting stem cell states the solution to overcoming chemoresistance?
Our previous work revealed the biological roles of stem cell markers LGR5 and LGR4 during development and in adult intestinal stem cells (ISCs). These GPCR family members are co-expressed in ISCs and play distinct roles in maintaining ISC survival and differentiation through the Wnt/β-catenin pathway. In contrast, LGR6 is not expressed in normal intestinal tissue. In other organs (skin, kidney, nails), LGR6 marks stem cells involved in tissue development and repair.
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. About one-third of patients treated with surgery relapse, and the 5-year survival rate remains low (14.7%). Identifying new molecular targets for treating chemo-resistant CRC is therefore critical.
Single-cell RNA sequencing shows that LGR4, LGR5, and LGR6 mark tumor stem-like cells in CRC. LGR6 has been suggested as a prognostic marker for aggressive tumors, but its role in cancer stemness is still unclear. Our recent findings suggest that LGR6 may influence tumor stemness and response to chemotherapy. Understanding LGR6 signaling could open new therapeutic avenues for CRC.
Project:
This PhD project will study how LGR6 influences tumor stem-like cells and chemoresistance, using advanced models: organoid systems (including human patient-derived tumor organoids), mouse models, and molecular biology techniques. Bioinformatics and biochemical approaches will be used to uncover signaling mechanisms.
Joining our laboratory offers:
– a dynamic international research environment with strong expertise in intestinal stem cell biology, organoid systems, and state-of-the-art technologies.
– collaborative projects within the GHoPaT group (GPCR in Homeostasis & Pathology),
– weekly scientific meetings for PhD students of the GHoPaT group
– personalized mentoring for career development.
Candidate profile:
Highly motivated, independent organizational skills, with strong collaborative abilities
Strong interest in cancer biology, stem cells, and molecular mechanisms.
Skills in cell culture, molecular biology, or bioinformatics are a plus.
Excellent English level