is researching the role of immune system in intractable human diseases, particularly in autoimmunity cancer and inflammation.
The research investigates the fundamental roles of immune cells, their receptors and their antibodies, and how these can be manipulated for the treatment of human disease.
The research program involves basic, applied and translational projects that have led to fundamental discoveries of immune function and to the subsequent development of potential biological and drug therapeutics for the treatment of inflammation, cancer or infection.
Translational projects are examining human receptor gene polymorphisms and protein biomarkers associated with disease.
The applied projects have resulted in new monoclonal antibodies, recombinant engineered receptor proteins as well as designer drugs.
This successful research has been based on fundamental studies of human immune cell function and animal models of disease.
We have extensively investigated the biochemistry, structure and function of major genes and proteins involved in immunity principally studies of cell surface molecules – the mouse Ly antigens and human CD antigens especially the immunoglobulin Fc Receptors.
Recent work has defined the role of antibody based effector systems in tissue inflammation in allergy and auto-immune diseases such as rheumatoid arthritis and lupus.
Collectively these are long-standing investigations into the role of Fc receptors has defined them to be one of the most important families of cell surface molecules involved in immune responses.
These receptors (antibody receptors) play central roles in normal immune function – resistance to infection and regulation of antibody production and together with new monoclonal antibodies drugs can be harnessed for the treatment of cancer, infection and inflammation.
Because the immune system has such broa
Project Title: The Action of Therapeutic Antibodies and FcR In Cancer and Inflammation Supervisor: Professor P. Mark Hogarth, Email: Mark.Hogarth@burnet.edu.au ; https://www.burnet.edu.au/people/182_mark_hogarth Telephone: 0419345016 MRI &/or Location: Burnet Institute; Alfred Hospital Co-Supervisor(s): Dr Theo Mantamadiotis; Dr Graham MacKay Project Description: Therapeutic monoclonal antibodies (mAb) have revolutionised the treatment of many human cancers, inflammatory diseases and infectious disease. In many cases mAb potentcy is dependent on their activation of specific cell surface receptors called Fc receptors (FcR). This PhD project will define how human FcR are engaged by therapeutic antibodies to initiate the responses that lead to their therapeutic action. The project will focus on the main actions of human Fc receptors: 1) Cell killing (ADCC), by the “activating-type” Fc receptors which permits direct killing of cancer or virus-infected cells 2) FcR cooperation that leads to inhibition of inflammatory disease by the inhibitory-type FcR dampens the destructive inflammation found in autoimmunity and allergy. The project may be modified to fit the students interests. The research can be applied to developing new human therapeutic mAbs by understanding and manipulating the FcR function on killer cells and other cell types. The projects will use molecular genetics, flow cytometry, antibody engineering, protein expression, immune cell function and the number of other major technologies. The Hogarth laboratory has made major discoveries in human Fc receptor biology, structure and function and has applied these in the development of new biotherapeutics for human disease. REF: Hogarth and Pietersz Nature Reviews Drug Discovery 11: 311-331, 2012. doi: 10.1038/nrd2909.