Laureate Professor Colin L. Masters CV - Mental Health Research ...

COLIN L MASTERS
Curriculum Vitae (abbreviated – 5 pages)
November, 2011
DATE AND February 5, 1947
PLACE OF BIRTH: Perth, Australia
CITIZENSHIP: Australian
ADDRESS:
The Mental Health Research Institute
Kenneth Myer Building
The University of Melbourne
Parkville, Victoria, Australia, 3010
Tel: +61 3 9035 6575
E-mail: c.masters@unimelb.edu.au
CURRENT SUBSTANTIVE ACADEMIC AND PROFESSIONAL APPOINTMENTS:
Executive Director, Mental Health Research Institute (2007-).
Laureate Professor of Neuroscience, The University of Melbourne (2002-).
Consultant, The Royal Melbourne Hospital and Melbourne Health (1989-).
Co-Director, Australian National Creutzfeldt-Jakob Disease Case Registry (1993-).
TERTIARY EDUCATION:
1967 B.Med.Sci.(Physiology) (First Class
Honours), University of Western Australia.
1970 M.B., B.S., University of Western Australia.
1977 M.D., University of Western Australia.
ACADEMIES AND COLLEGES:
Fellow Royal College of Pathologists (1986).
Fellow The Royal College of Pathologists of
Australasia (1989).
Fellow Australian Academy of Science (1999).
Fellow Australian Academy of Technological
Sciences and Engineering (2007).
Member Academy of the National Health and
Medical Research Council of Australia
(2010).
PROFESSIONAL AND ACADEMIC HISTORY:
1964 Commenced undergraduate studies at the University of Western Australia.
1966 Research student, Department of Physiology, University of Western Australia.
1968 Research Student examining the pathology of “slow virus diseases” of the nervous system.
Departments of Pathology and Microbiology, University of Western Australia.
1970 - 1971 Clinical work with the Missionaries of Charity Sisters (Mother Theresa) and Brothers (Ian
Travers-Ball SJ, Brother Andrew) Calcutta, India.
1971 - 1974 Resident Medical Officer, Royal Perth Hospital, Perth.
1972 - 1974 Research Fellow, Department of Pathology, University of Western Australia. Dr. Michael
Alpers, Dr. Byron Kakulas (Supported by Faculty of Medicine Research Fellowship).
1973 - 1976 Co-founder and Medical Officer (Part-time), Aboriginal Medical Service, Perth (The Aboriginal
Medical Clinic, 201 Beaufort St, Perth 6000).
1975 - 1976 Medical Registrar, Sir Charles Gairdner Hospital, Perth (General Medicine, Immunology and
Neurology).
1976 Research Fellow, Department of Pathology, University of Western Australia, Perth (Supported
by Faculty of Medicine Research Fellowship).
1976-1977 Research Fellow, Neuropathology, Massachusetts General Hospital, and Harvard Medical
School, Boston. Dr. E.P. Richardson, Jr.
1977-1980 Visiting Scientist, Laboratory of Central Nervous System Studies, National Institutes of
Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda.
Dr. D. Carleton Gajdusek.
1980-1981 Guest Professor and Humboldt Fellow, Institute of Neurobiology, University of Heidelberg,
Germany. Dr. Melitta Schachner.
1981-1988 Principal Research Fellow, National Health and Medical Research Council of Australia,
Department of Pathology, University of Western Australia.
1981-1988 Co-founder, Alzheimer’s Disease Association (Western Australia).
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1981-1988 Clinical Assistant (Research), Department of Neuropathology, Royal Perth Hospital.
1988 Overseas study leave. Center for Molecular Biology, University of Heidelberg. Prof. Konrad
Beyreuther.
1989-2006 Professor, and Head of Department of Pathology, The University of Melbourne.
1989-2006 Consultant, Chief of Neuropathology Laboratory, and Chair, Senior Scientists’ Council, Mental
Health Research Institute of Victoria.
1989-2006 Consultant, The Royal Melbourne Hospital and Committee Member of the Executive of the
Melbourne Health Shared Pathology Services.
1999-2005 Associate Dean (Research), Faculty of Medicine, Dentistry and Health Sciences, The University
of Melbourne.
2002- Laureate Professor of Neuroscience, The University of Melbourne.
2007- Executive Director, Mental Health Research Institute.
2008 - 2009 Chair, Directors Coordination Forum, Melbourne Neuroscience Project.
EDITORIAL BOARDS:
American Journal of Alzheimer’s Disease and Other Dementias (1997 -)
Annals of Neurosciences (2009 -)
Archives of Neurology, International Advisory Committee (1996 -)
Brain Ageing (2002 -)
Brain Research (1994 -)
Current Alzheimer Research (2003 -)
Dementia and Geriatric Cognitive Disorders (1989 -)
International Journal of Biochemistry and Cell Biology (2006-)
Journal of Alzheimer’s Disease (1997 -)
Journal of Clinical Neuroscience (1994 -)
Journal of Molecular Neurodegeneration (2005-)
Neurodegenerative Diseases (2002 -)
Neuropathology (1997 -)
Research and Perspectives in Alzheimer’s Disease (Foundation IPSEN) (1990 -)
Translational Psychiatry (2011 - )
ADVISORY AND EXECUTIVE COMMITTEE MEMBERSHIPS:
Alzheimer’s Disease International. Medical and Scientific Advisory Panel.
Australian Imaging Biomarkers and Lifestyle (AIBL) study, Management Committee
Australian National Creutzfeldt-Jakob Disease Case Registry Co-Director (1993-).
Centre for Neuroscience, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne.
Management Advisory Board and Member of Executive Committee.
Creutzfeldt-Jakob Disease Registry Advisory Group, Commonwealth Department of Health and Aging (Chair)
(2003-).
Dominantly Inherited Alzheimer Network (DIAN), Steering Committee.
Directors Coordination Forum, Melbourne Neuroscience Project (2008-).
Fondation Alliance BioSecure. Scientific Advisory Board (2009-).
Infection Control Steering Committee, Communicable Diseases Network Australia New Zealand (CDNANZ).
International Conference on Alzheimer’s Disease and Related Disorders. International Scientific Advisory
Committee.
International Conference on Alzheimer’s and Parkinson’s Disease. Scientific Advisory Board (2005-).
International Society to Advance Alzheimer Research and Treatment (ISTAART) Advisory Council (2009-).
Melbourne Theatre Company, Board Member (2006-).
National Health and Medical Research Council. Transmissible Spongiform Encephalopathies Advisory Committee
(Deputy Chair 2000-2010), (Chair 2010-2012).
Neuroscience Victoria, member Board of Directors.
Prana Biotechnology. Scientific Advisory Board (2007-).
Van Cleef/ Roet Centre for Nervous Diseases, Monash University. Advisory Board.
World Federation of Neurology Research Group on Dementia. Executive Committee.
World Federation of Societies of Biological Psychiatry (WFSBP), Task Force on Dementia (2004-).
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HONORS, PRIZES, NAMED AND INVITED LECTURES, AND OTHER SPECIAL SCIENTIFIC
RECOGNITION:
1988 Dr. Gunther Buch prize (with Konrad Beyreuther).
Robert Pfleger Prize (with Konrad Beyreuther).
1990 American Academy of Neurology, Potamkin Prize (with Konrad Beyreuther).
1991 Max Planck Research Award from the Alexander von Humboldt Foundation (with Konrad
Beyreuther).
1993 Chairman, Foundation IPSEN Meeting on “βA4 Amyloid Protein Precursor in Development, Aging
and Alzheimer’s Disease” (Lyon).
Fellow, Brain-Behaviour Research Institute, LaTrobe University.
1995 Convenor, International Workshop on Creutzfeldt-Jakob Disease (Melbourne).
KJ Zülch Prize (with Konrad Beyreuther) from the Gertrud Reemtsma Stiftung of the Max Planck
Society (Cologne).
1996 WHO Consultation on Clinical and Neuropathological Characteristics of the New Variant of
Creutzfeldt-Jakob disease and other human and animal transmissible spongiform Encephalopathies
(Geneva).
1997 King Faisal International Prize in Medicine (with Konrad Beyreuther and James Gusella).
George S Christie Lecture, Australasian Society for Experimental Pathology.
Erna Struckmann Lecture, Centre for Molecular Biology, The University of Heidelberg.
Chairperson, WHO Consultation on Medical and other Products in Relation to Human and Animal
Transmissible Spongiform Encephalopathies (Geneva).
1998 Alois Alzheimer Award (University of Munich).
1999 WHO Consultation on Diagnostic Procedures for Transmissible Spongiform Encephalopathies and
WHO Consultation on Caring for Patients and Hospital Infection Control in Relation to Human
Transmissible Spongiform Encephalopathies (Geneva).
2000 IPSEN Foundation: convenor of Symposium on Neurodegeneration (Paris).
2001 Bethlehem Griffiths Research Foundation Medal.
Australian Citation Laureate (1981-1998), ISI Thompson Scientific Award.
2002 Mayne Florey Medal Award.
Laureate Professor, The University of Melbourne.
2003 Halford Oration, The University of Melbourne.
Alzheimer’s Australia WA, Life Membership.
2004 Vernon Plueckhahn Oration, Geelong Hospital.
Boehringer – Ingleheim Lecture (University of Maniz)
Guest Scientist, Biomedical Research Council, Singapore
2005 Fulton Symposium Soriano Lecture, World Congress of Neurology (Sydney)
2006 Lennox K. Black Prize (Thomas Jefferson University, Philadelphia).
Lifetime Achievement Award in Alzheimer’s Disease Research (Alzheimer’s Association).
Grand Hamdan International Award for Medical Sciences in the field of Molecular and Cellular
Pathology of Neurological Disorders, (Dubai).
Honorary Chief-Elect, Ikoro II of Ogborland, Ogbor Autonomous Community, Ihitteafoukwu,
Ahiazu Mbaisc, Imo State, (Nigeria).
2007 Victoria Prize from the Minister for Innovation, State Government of Victoria and the Smorgon
Foundation
2008 Honorary Doctor of Letters, University of Western Australia.
2009 Leach Lecture and Medal, Lorne Conference on Protein Structure and Function.
2011 CSIRO Medal for Research Achievement.
Citation record: h-factor (ISI-Thomson Scientific) at 19 July, 2011 = 87
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CAREER SUMMARY
Masters began his research career as a 1966 summer student working with Evan Morgan (Physiology,
The University of Western Australia) on the placental transfer of plasma proteins. His interests in neuroscience
stem from this time, when he then took the opportunity to pursue a Bachelor of Medical Science degree with
Brian Johnstone and Judith Laszlo, resulting in the first demonstration of brain-stem evoked responses to
auditory stimuli in humans.
Toward the end of 1967, MacFarlane Burnet gave a lecture in Perth on kuru. This, together with the
connections that Byron Kakulas and Michael Alpers (both at the University of Western Australia in Perth) had
established with D. Carleton Gajdusek and Clarence J. Gibbs at the NIH, led to Masters’ ongoing study of the
transmissible spongiform encephalopathies (prion diseases). These studies began with the pathologic evaluation
of preclinical disease, and continued with studies on the nature of spongiform change (with E.P. Richardson,
Harvard Medical School). Studies followed on the epidemiology of Creutzfeldt-Jakob disease, the familial
patterns of these diseases, and the identification of a special subgroup (the Gerstmann-Sträussler syndrome
[GSS]) in which abundant amyloid deposition is a hallmark. The delineation of GSS gave an important lead to
the first demonstration by Prusiner and colleagues of a pathogenic mutation in a gene coding for prion protein.
The evaluation of amyloid protein deposition in transmissible prion diseases (subsequently shown by
Prusiner and colleagues to be comprised of the PrP, or prion protein) led Masters to begin to study the nature of
the amyloid deposits found in the brain in Alzheimer’s disease (AD) in 1978. Amyloid protein was first purified
from neuritic plaques in 1979, and described in 1983. However, it was not until a collaboration was formed in
1984 between Masters and Konrad Beyreuther (then at the Institute of Genetics, Cologne) that the N-terminal
sequence of the Alzheimer plaque amyloid was obtained, at the same time as the N-terminal sequence of
vascular amyloid was determined by George Glenner (with whom Masters had also collaborated).
These studies over the period 1978-1988 set the scene for Masters’ research directions when he moved
to the University of Melbourne in 1989. There, his research evolved into developing therapeutic strategies based
around the central amyloidogenic pathway in AD. Two principal strands emerged, one attempting the inhibition
of the γ- and β-secretases which release the Aβ peptide from APP, the other deriving from the observations on
an important interaction between metal ions and APP/Aβ.
As the real potential for development of pharmaceuticals that could delay the onset of AD, or slow its
progression, became apparent, Masters initiated collaborations with major pharmaceutical companies
SmithKline Beecham and Merck. These first focussed on the identification of the α- and β-secretases, as these
play a key role in the generation of the N-terminus of β-amyloid in the brain, and subsequently on the
development of powerful specific inhibitors of the presenilin complex associated with γ-secretase activity.
Those collaborative studies have been brought to a point where Phase 3 clinical trials are in progress.
Masters and colleagues then developed a parallel strategy around studies of the toxic gain-of-function of
Aβ amyloid as it accumulates in the brain, reasoning that compounds directed to interfere with the dominant
negative property of Aβ might provide a different but complementary approach to that utilising secretase
inhibition. This strategy is proving to be of great promise. One mechanism by which Aβ exerts its toxic effect is
through oxidative damage when Aβ amyloid comes into contact with redox active metal ions such as Cu 2+ .
Toxic soluble oligomers of Aβ are now thought to aggregate within and on membranes of neurons. Masters’
group has identified compounds that prevent Cu 2+ interacting with Aβ, and have the additional desirable
properties of abrogating the generation of H 2 O 2 and at the same time causing solubilisation of polymerised Aβ.
Such compounds have been tested in experimental models of AD with positive results. Two compounds have
been trialled in Phase 2a studies in humans with mild to moderate AD. If confirmed in larger (Phase 2b/3)
studies, this may become one of the first pharmacological interventions to test the Aβ theory of AD.
With the emergence of variant forms of CJD as a major threat to public health, Masters re-established a
research group on prion dementias. He brought the knowledge gained from his AD studies, particularly with
respect to the roles of metal ions, to bear on the problem of PrP toxic gain-of-function. This may also lead to
new approaches to therapy for the prion dementias, for which there are no effective treatments at present. He
has a major commitment to public policy and is an active contributor to Government committees on variant CJD
in both the UK and Australia, helping in efforts to deal with this threat.
In summary, Masters’ career has come full circle, from the pathological study of human brain disease to
clinical trials, and from discovery and characterisation of the Aβ aggregation in AD, to the development of a
coherent theory on the mechanisms of Aβ amyloid production and its role in causation of neurodegeneration.
This theory has become the generally accepted paradigm for investigating Alzheimer disease. The single, most
characteristic, feature of Masters’ research has been the way in which he has approached gene and protein
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structure and function for a variety of diseases caused by proteins that aggregate in the adult human brain. He
has used the resulting data to generate a rich variety of discoveries that have had a wide impact in understanding
normal and abnormal brain function in disease and in ageing. In the best traditions of translational research,
Masters has continued to identify and develop effective rational therapeutic and diagnostic strategies for disease
modification, perhaps even prevention.
For these discoveries, Masters has won many prestigious prizes and awards, including the Potamkin Prize of the
American Academy of Neurology (1990), the Max Planck Award of the von Humboldt Foundation (1991), the
Zülch prize of the Max Planck Society (1995), the Faisal International Prize (1997), the Alzheimer Award from
the University of Munich (1998), the Lennox K Black Prize from Thomas Jefferson University (2006), the
Grand Hamdan International Award (2006), and the Victoria Prize from the Minister for Innovation, State
Government of Victoria and the Smorgon Foundation. In 2008 he was awarded the Honorary Degree of Doctor
of Letters from the University of Western Australia. He is active in the Australian Academy of Science (AAS)
and the Australian Academy of Technological Sciences and Engineering (AATSE), and continues to lecture
widely at undergraduate and postgraduate levels. He has been appointed by the Australian Government as Chair
of the National Health Committee, principal committee of the National Health and Medical Research Council of
Australia.
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