Philippe Roux and his team seek to understand the molecular mechanisms by which oncogenes transform a normal cell into a cancerous one. This knowledge is crucial for the discovery of novel therapeutic targets and to decipher the molecular causes of resistance to treatment.
Signal transduction mechanisms are instrumental for cells to integrate signals from the external environment and to generate adapted responses. Deregulation of these mechanisms owing to mutations in specific signaling proteins will bring about various pathologies. One of the best and most lethal examples is cancer, which often results from mutations that activate proto-oncogenes (e.g., KRAS, BRAF, PIK3CA) or inactivate tumor suppressor genes (e.g., PTEN, APC, TP53). The objective of the Roux laboratory is to decode the signaling networks within cancer cells to facilitate the development of new anti-cancer treatments.
An important objective of the Roux laboratory is to identify novel effectors of the RAS/MAPK pathway, which is frequently upregulated in human cancer. Melanoma is particularly dependent on the RAS/MAPK pathway, as more than ~ 85% of tumors display mutations affecting one of its components (e.g., BRAF, NRAS, NF1). To better characterize the RAS/MAPK pathway in melanoma and to identify crucial effectors, the Roux laboratory uses several proteomic approaches, including phosphoproteomics and proximity-dependent biotin identification (BioID). Using these methods, they have identified several new effectors of the RAS/MAPK pathway and plan to characterize their biological functions and potential value as novel therapeutic targets.
Another important objective of the Roux laboratory is to identify novel cancer cell vulnerabilities conferred by activated oncogenes. To better understand the role of oncogenic signaling in tumorigenesis and drug resistance, they have developed several cellular models harboring some of the main activated oncogenes found in human cancers. Using a proteogenomics approach relying on transcriptomics, proteomics and CRISPR-based functional screening, the Roux laboratory seeks to identify potential vulnerabilities associated with the KRAS, PIK3CA, MYC and HER2 oncogenes.
Lastly, the Roux laboratory seeks to identify new diagnostic tools and immunotherapeutic targets in adult and pediatric leukemia. The use of antibody therapies in human diseases, in particular cancer, is gaining importance, but a major technical challenge is finding the few cell-surface proteins that provide distinguishing marks for specific cancer types. Recent advances in chemoproteomics have begun to overcome these limitations by combining chemical tagging of cell-surface proteins with affinity purification-mass spectrometry (AP-MS). The Roux laboratory has adapted these approaches to simultaneously identify and quantify cell-surface antigens from primary acute myeloid leukemia (AML) specimens. A major objective of Philippe Roux’s team is to characterize these potential targets and develop antibody-based immunotherapy.