Pathogenesis of inflammatory disease

1. Chronic or inappropriate inflammatory responses contribute to the pathogenesis of several diseases including psoriasis and arthritis.  Important scientific advances indicate that the progression of these diseases may result from a switch in the type of cells which are present at sites of inflammation which ultimately leads to damage and destruction of the affected tissue.  A major focus of this research programme is to understand the events and mechanisms involved in switching cells during the inflammatory response. A thorough understanding of these processes may assist in the diagnosis of inflammatory disease and facilitate the introduction of effective treatments in the early stages of disease. The study of inflamed tissue and derived cells represents a central feature of this research programme which will provide information with important clinical significance. Furthermore, these studies may potentially open new avenues for the treatment of chronic inflammatory disease.

2. Long-term physiologic stress responses are achieved by integration of the autonomic nervous, HPA, cardiovascular, metabolic and immune protective responses. Achieving this dynamic stability requires considerable "tissue wear and tear" resulting from sustained overactivity (or underactivity) of these systems. Disturbances in endocrine-immune interactions upset the normal regulatory homeostatic balance and may alter susceptibility to a variety of disease states associated with immune dysregulation. Inflammatory stimuli reliably elicit HPA activation, and it is now established that the immune and HPA systems are mutually regulatory and that their interactions partly determine stress effects on immune function. What has not been extensively studied, however, is the interactive nature of the endocrine and immune systems and whether this might alter predisposition to inflammatory disease or stress-related pathologies. The long-term aim of this research programme is to further explore the physiological and molecular interactions occurring at the neuroendocrine-immune interface.

Key areas of interest include:

• Acute and chronic inflammation
• Cytokine action
• Signal transduction
• Orphan nuclear receptors
• Gene transcription

Postgraduate Teaching

Neuroimmunology: Long-term physiologic stress responses are achieved by integration of the autonomic nervous, hypothalamic-pituitary-adrenal  (HPA) axis, cardiovascular, metabolic and immune protective responses.  Achieving this dynamic stability requires considerable ¿tissue wear and tear¿ resulting from sustained overactivity (or underactivity) of these systems. Disturbances in endocrine-immune interactions upset the normal regulatory homeostatic balance and may alter susceptibility to a variety of disease states associated with immune dysregulation.  Inflammatory stimuli reliably elicit HPA activation, and it is now established that the immune and HPA systems are mutually regulatory and that their interactions partly determine stress effects on immune function.  In this lecture, we will discuss the interactive nature of the endocrine and immune systems and whether this might alter predisposition to inflammatory disease or stress-related pathologies.

Primary supervision of following postgraduate fellows and students

2011-             Dr Daniel Crean, Postdoctoral Fellow 
2006-2010      Dr Jason McMorrow, Postdoctoral Fellow
2004-2007      Dr Kim Mix, Postdoctoral Fellow
2005-2006      Dr Darren Ennis, Postdoctoral Fellow
2005-2007      Dr Marina O'Kane, MD Fellow
2002-2003      Dr Alice McEvoy, Postdoctoral Fellow

2011-             Aisling Smyth, PhD student
2010-             Alyssa Gilmore, PhD student
2007-2011      Viviana Marzaioli, PhD student
2005-2009      Davide Zocco, PhD student
2003-2007      Carol Aherne, PhD student
2001-2005      Jennifer Ralph, PhD student
1998-2002      Alice McEvoy, PhD student

UCD Collaborators

Dr Jason McMorrow, School of Agriculture, Food Science and Veterinary Medicine.

Dr Sinead Ryan, School of Agriculture, Food Science and Veterinary Medicine.

Professor David Brayden, School of Agriculture, Food Science and Veterinary Medicine.

Professor Oliver FitzGerald, School of Medicine and Medical Sciences.

Dr Alice McEvoy, School of Biology, Dublin Institute of Technology.

Professor Paul Murphy, School of Chemistry. National University Ireland-Galway.

Professor Bruce Cronstein, School of Medicine, New York University.
 
Professor Kim Mix, Department of Biological Sciences, Loyola University, New Orleans. 

Undergraduate Teaching

Cell and whole body Metabolism This module focuses on the pathways of intermediary metabolism. It describes how metabolism is a highly coordinated and directed cell activity, in which many multi-enzyme systems (cell and molecular module) co-operate to obtain chemical energy by degrading energy rich nutrients; convert nutrient molecules into the cells own characteristic molecules; polymerize monomeric precursors into proteins, nucleic acids, lipids, polysaccharides and other cell components; and synthesize and degrade biomolecules required in specialised cellular functions.

Cell Proliferation and Cancer These lectures describe how multi-cellular organization in animals depends on co-operative behaviour of cells making up the organism. Differentiation gives rise to populations of cells which specialize in specific functions, e.g. muscles, neurons, epithelia etc. Larger, more complex organisms such as vertebrates may specify cell differentiation and behaviour in terms of populations of cells rather than individuals, but in all cases, within the mature organism, cells refrain from exerting their intrinsic potential to grow and divide beyond territories and patterns laid down in the overall developmental plan.This cooperative behaviour depends on communication between cells, so that each cell can sense its place in the developmental pattern, and cell growth and proliferation can be co-ordinated with the needs of the organism. Cancer cells break the most basic rules of behaviour by which multi-cellular organisms are built and maintained, and they exploit every kind of opportunity to do so.

Integrated Physiological Communication These lectures integrate and develop our understanding of how cell-cell and tissue communication is important to animals. The endocrine system is used as an exemplar of co-ordinated signalling which incorporates feedback patterns, hormones and hormone receptors, cellular responses and disturbed function. The module interprets the role(s) of hormones including adrenal glucocorticoids, thyroid hormones and growth hormone. In addition the endocrine control of metabolism, growth and calcium balance is discussed.

Modules Coordinated:
VET 20080 and VET 30380