The mission of the Najafov Lab is to understand the role of cell death in physiology and disease. Our research is focused on necroptosis and how it can be targeted to develop novel strategies for treating cancer.
Necroptosis is a major necrotic and inflammatory cell death linked to various human diseases, including cancer, inflammatory bowel disease, liver injury, pancreatitis, neurodegenerative disorders, and various viral and bacterial infections. Necroptosis signaling is mediated by the activation of RIPK1 and RIPK3 kinases downstream of pro-inflammatory ligands such as TNF, or downstream of microbial danger-associated molecules. The execution of necroptosis occurs through cell membrane rupture by large pores formed via RIPK3-triggered phosphorylation and tetramerization of a pseudokinase MLKL.
Anti-tumor immunity is key for achieving a sustained remission and eradication of metastasized tumors. Necroptosis is immunogenic and necroptosis of cancer cells can be harnessed to potentiate immunotherapies. Therefore, a fundamental understanding of necroptosis regulation in the context of cancer and anti-tumor immunity could pave the way for the development of future cancer immunotherapies and cancer vaccines.
We are interested in answering these fundamental questions: