The 2006 GE Healthcare Bio-Sciences Award: Philip Hogg

Philip HoggPhilip Hogg is an NHMRC Senior Principal Research Fellow and Professor in the Centre for Vascular Research at the University of New South Wales. He heads the Allosteric Disulphide Group. Philip is a graduate from the Department of Biochemistry, University of Queensland. His doctoral studies were in the lab of Professor Don Winzor and his thesis examined the consequences of ligand bivalency in binding studies. He graduated in 1987 and then worked as a postdoctoral fellow in the labs of Professor Craig Jackson in the USA and Professor Johan Stenflo in Sweden, where he studied the kinetics and protein chemistry of blood coagulation. He returned to the Department of Haematology at the Prince of Wales Hospital, Sydney, in 1991 and the Centre for Vascular Research was established shortly thereafter. His lab and most of the Centre moved to the University of New South Wales campus in 1994.

In the mid-1990s he was working on thrombospondin, a secreted protein that inhibits new blood vessel formation (angiogenesis), when he discovered that its activity is regulated by intramolecular thiol-disulphide exchange. He found this intriguing and wondered whether other secreted proteins are controlled in this way. His research efforts have led to the characterisation of a type of disulphide bond he has called the allosteric disulphide. Allosteric disulphides control protein function by triggering a conformational change when they break and/or form. He has predicted that about one in fifteen of all structurally determined disulphides is a potential allosteric bond, implying a significant role for these bonds in controlling protein function. Viral, bacterial and human proteins have now been shown to be controlled by these bonds. His research aims are to characterise control of important proteins by allosteric disulphides, be able to reliably predict allosteric disulphides in proteins, and to exploit allosteric disulphides for drug development. Work on the last aim has led to the development of two novel anti-cancer drugs that will be tested in clinical trials in cancer patients in 2006-2008. Both are small synthetic compounds that react with allosteric disulphides. A biotechnology company, Cystemix Pty Ltd, has been formed to manage the commercial development of these drugs.