Head of Division
Pat Holt PhD FRCPath(UK) DSc FAA

Professor Holt established the Division of Cell Biology in 1990. He is currently Senior Principal Research Fellow, NHMRC and holds a Professorship at the University of Western Australia. Previous appointments include Acting Director, Clinical Immunology Research Unit, Princess Margaret Hospital for Children; and Research Fellow, Institute of Environmental Hygiene, University of Gothenburg.

Divisional Summary
The research focus in the Division of Cell Biology continues to be upon the cellular and molecular mechanisms underlying susceptibility and resistance to infections and allergic diseases in the respiratory tract during childhood.  Earlier work from the Division has established the important paradigm  that risk for postnatal development of atopy and asthma is determined primarily by maturational factors which control the transition of the immune system from the low activity state which is characteristic of fetal life, to the fully functional state seen in later childhood.  The key to this transition is the maturation of a variety of cytokine driven effector functions which are suppressed in utero in order to protect the placenta from inflammatory damage.  These same mechanisms are necessary for resistance to both infections and allergy, and we have shown that the rate at which they mature functionally during the preschool years is a key determinant of risk for allergy, respiratory infection and asthma.  Much of the work of the Division remains targeted at more detailed definition of these mechanisms, with the aim of development of early intervention strategies to reduce disease susceptibility, ideally to prevent disease onset.  This includes a significant component devoted to pediatric vaccinology, as many of the underlying immunological principles in this area relate also to asthma/allergy susceptibility. An important complementary stream of research in our Division is aimed at elucidating the mechanisms that regulate the cell populations responsible for triggering T-lymphocyte activation during the “late phase response” in asthma, which is largely responsible for progression from acute to chronic disease.  Earlier work from the Division has identified the principal cellular trigger of this response, airway mucosal Dendritic Cells, and most recently we have shown that their pro-inflammatory functions are in turn controlled locally by T regulatory cells.  Our ongoing studies in this area are aimed at determining the role of these cells as determinants of susceptibility to atopy/airway hyper-responsiveness in “high risk” strains of rats.  We have also developed a program on new therapeutic strategies to dampen the pro-inflammatory functions of these Dendritic Cells in asthmatics.

Contact
Email - patrick@ichr.uwa.edu.au

Phone - +61 8 9489 7777

Fax - +61 8 9489 7700