This project is a continuation of a line of investigation we started more than 20 years ago. We then discovered a protein, called NF-KB, that subsequent work has shown to playa key role in inflammation and immunity. Here we propose four lines of investigation (aims) that seek to increase our knowledge of the roles of NF-KB in the inflammatory response. Inflammation is a process that continues for days following an initiating stimulus and NF-KB plays a role throughout:
our first aim i s to understand the temporal control processes that allow the inflammatory response to unfold in an orderly manner.
Our second aim i s to probe the role played by an enigmatic regulator of NF-KB responses called B94. It potentiates induction of some genes by NF-KB but there is no mechanistic or physiological understanding of its effects. NF-KB is extensively modified as part of its mode of action: our final two aims are to investigate previously uncharacterized modifications for which we have preliminary indications of importance: methylation and glycosylation.
Realization of these four aims will significantly increase our understanding of the inflammatory response that underlies the body's ability to fight infections. Chronic, unregulated inflammation is thought be involved in cancer, heart disease, autoimmunity and other conditions;this work will also help to understand and hopefully treat these ailments.
Showing the most recent 10 out of 52 publications
