Prince Henry’s Institute

 

Craig Harrison

 

Appointments

• NHMRC RD Wright Fellow

• Honorary Lecturer, Department of Biochemistry and Molecular Biology, Monash University

 

Profile

Dr Harrison gained his PhD in Immunology from the University of New South Wales in 1999 and joined PHI as a TM Ramsay Fellow. He continued his postdoctoral training at the Salk Institute (La Jolla, CA) while a CJ Martin Research Fellow of the NHMRC.

In 2004, Dr Harrison returned to Prince Henry’s Institute where he heads the Growth Factor Signalling Laboratory. His current research interests relate to the structural and functional characterisation of TGFβ ligands, with particular reference to their roles in reproduction. In 2007 he was awarded a RD Wright Fellowship from the NHMRC.

 

Research Interests

The transforming growth factor β (TGF-β) superfamily comprises 33 structurally-related proteins in human, including the TGF-β, activin, bone morphogenetic protein (BMP), growth differentiation factor (GDF) and nodal-related families. These proteins are ubiquitous and essential regulators of cellular processes including proliferation, differentiation, migration, and survival, as well as physiological processes, including embryonic development, angiogenesis, and wound healing. Not surprisingly, therefore, subversion of signalling by TGF-β family members has been implicated in many human diseases, including developmental disorders, cancer, fibrosis, autoimmune and vascular diseases.

Our laboratory is interested in understanding the processes that promote signalling specificity and diversity across the TGF-β family. In particular we are focusing on the roles of:

(i) co-receptors, which control the access of TGF-β ligands to signalling receptors;

(ii) secreted antagonists that sequester TGF-β ligands and inhibit signalling;

(iii) extracellular matrix components that govern the availability of active TGF-β ligands.

These studies are important, as dysregulation of these processes results in either an excess or a deficiency of specific TGF-β ligands leading to human disease.

 

Expertise

reproductive endocrinology, structure/function analysis, protein purification, molecular biology, cell culture, inhibin, activin, TGF-β, nodal myostatin

 

Recent Achievements

• Developed the first activin type II receptor antagonist with collaborators at the Salk Institute.

• Explored the biological activities of the reproductive hormones, inhibin A and B

• 2006-2008  Awarded a New Investigator Project Grant  to investigate the therapeutic utility of blocking the activin signalling pathway in fibrosis and cancer.

• 2007-2011  Awarded an NHMRC RD Wright Fellowship

 

Current Research

• Inhibin A and B in the reproductive system

• TGF-β signalling pathway disorders

• Myostatin and muscular dystrophy

 

Selected Publications

Walton KL, Makanji Y, Wilce MC, Chan KL, Robertson DM, Harrison CA. A common biosynthetic pathway governs the dimerization and secretion of inhibin and related transforming growth factor beta (TGFbeta) ligands. J Biol Chem. 2009 Apr 3;284(14):9311-20.

Makanji, Y., Walton, K., Wilce, M., Chan, K., Robertson, D. & Harrison, C.A. Suppression of inhibin A biological activity by alterations in the binding site for betaglycan. J Biol Chem 2008 Jun 13;283(24):16743-51

Makanji, Y., Harrison, C.A., Stanton, P.G., Krishna. R., and Robertson, D.M. Inhibin A and B in vitro bioactivities are modified by their degree of glycosylation and their affinity to betaglycan. Endocrinology, 2007 148(5):2309-2316

Harrison, C.A., Wiater, E., Lewis, K.A., Gray, P.C., and Vale, W.W. Identification of distinct inhibin and TGFbeta binding sites on betaglycan: functional separation of betaglycan co-receptor actions. J Biol Chem, 2006. 281:17011-22.

Harrison, C.A., Chan, K.L., and Robertson, D.M. Activin-A binds follistatin and type II receptors through overlapping binding sites: Generation of mutants with isolated binding activities Endocrinology, 2006. 147:2744-2753.

Harrison, C.A., Wiater, E., Lewis, K.A., Gray, P.C., and Vale, W.W. Identification of distinct inhibin and TGFbeta binding sites on betaglycan: functional separation of betaglycan co-receptor actions. J Biol Chem, 2006. 281:17011-22.

Harrison, C.A., Gray, P.C., Vale, W., and Robertson, D.M. Antagonists of activin signalling: mechanisms and potential biological applications. Trends in Endocrinology and Metabolism, 2005. 16: 73-78.

Harrison, C.A., Gray, P.C., Fischer, W., Donaldson, C., Choe, S., and Vale, W. An activin mutant with disrupted ALK4 binding blocks signaling via type II receptors. J Biol Chem, 2004. 279:28036-44.

Gray, P.C., Harrison, C.A., and Vale, W. Cripto forms a complex with activin and type II activin receptors and can block activin signaling. Proc Natl Acad Sci U S A, 2003. 100: 5193-8.

Harrison, C.A., Gray, P.C., Koerber, S.C., Fischer, W., and Vale, W. Identification of a functional binding site for activin on the type I receptor ALK4. J Biol Chem, 2003. 278: 21129-35.