STRESS-ACTIVATED PROTEIN KINASES IN HUMAN DISEASES

Our group studies the physiological and pathological functions of the p38MAPK family of mitogen-activated protein kinases. Our research focuses on:

• the discovery of new substrates, interacting proteins and inhibitors for these kinases, as well as study of their physiological roles using mice transgenic for distinct p38 isoforms, and

• the study of p38MAPK as a link between chronic inflammation and cancer, and as mediators of chronic inflammatory diseases.

Inflammation stands at the centre of many pathological (cancer) and natural (tissue repair) processes. It is well known that, in the right place and at the right time, controls a healthy host response, but uncontrolled inflammation is pathological. The main goal of this proposal is to expand our knowledge of the molecular mechanisms involved in the inflammatory response in the settings of: 1) chronic inflammation leading to tumour development (as in colon cancer associated to colitis); 2) pathogen infection by Candida albicans and 3) normal inflammatory resolution occurring in tissue repair/regeneration.

We are currently undertaking further studies to investigate the role of p38γ and p38δ in those processes. Our studies utilize biochemical, cell biology as well as whole animal model approaches using the genetically modified mice we have generated. Additionally, we are investigating the mechanism of p38γ and p38δ activation by inflammation and by pathogen infection, and how p38γ and p38δ regulation of cytokine and chemokine production in innate immune cells regulates inflammatory responses.