Checkpoints of the TNF signalling pathway: Implications in cancer and inflammation | Dr Najoua Lalaoui

TNF is a pleiotropic cytokine with key roles in inflammation. The TNF signalling is tightly controlled at multiple levels by diverse checkpoints. Removal of these checkpoints unleashes the cytotoxic potential of TNF than can be used for cancer therapy but also drive inflammatory diseases.

Dr Najoua Lalaoui
Senior Postdoc
Walter and Eliza Hall Institute of Medical Research

TNF (Tumor Necrosis Factor) is a master cytokine that induces survival, proliferation and cell death. The existence of these diverse outcomes is due to multiple checkpoints controlling the signalling cascade activated by TNF. RIPK1 is a major player in the TNF signalling cascade.

Dr Najoua Lalaoi and group have identified phosphorylation and cleavage of RIPK1 as belonging to crucial checkpoints. Disruption of these checkpoints switched the survival response to a cell death response. Identification of these checkpoint allowed us to propose a new therapeutic anti-cancer strategie as well as uncover a new inflammatory disease.

Dr Najoua Lalaoui is Victorian Cancer Agency Fellow and a Senior Postdoc at the Walter and Eliza Hall Institute of Medical Research. Her research focuses on understanding cell death pathways and cytokine signalling pathways.

During her PhD (2009), she investigated the molecular mechanism of the extrinsic apoptotic pathway induced by TRAIL. In 2010, she obtained a competitive French ARC Fellowship and joined Prof John Silke's group, where she studied regulators of the TNF signalling pathway, such as the E3 ligases IAPs and the kinase RIPK1. She has translated her findings in vivo using her extensive background in pre-clinical models of cancer and inflammation.

Her first and senior author publications on new regulatory mechanisms of the TNF signalling were published in high ranked journals (Nature, Cancer Cell, Mol Cell, Cell Death Diff). She also contributed to seminal discoveries in the field of cell death, cancer and inflammation (Cell, Immunity, Science Med Trans, Nature Com). She received multiple travel awards and the WEHI Kellaway Award for Excellence in Discovery. Her work was funded by competitive CI grants and fellowships (CIA in NHMRC, World Wide Cancer Research and Cancer Australia project grant, French ARC and  Victoria Cancer Agency Fellowships)