Professor Ian Frazer AC, FRS, FAA
|Professor Ian Frazer FRS|
As a child, Professor Ian Frazer liked to take things apart in order to see how they worked. “I liked the practical aspect of testing ideas with your hands,” he says, “and I was curious about how the world worked.”
It wasn’t long before Frazer knew he wanted to pursue a career in research. He went on to earn degrees in Medicine and Surgery from the University of Edinburgh in Scotland, then trained as a renal physician in order to investigate the immunological issues associated with transplantation. It was this growing interest that led him to the Walter and Eliza Hall Institute (WEHI) in Melbourne.
“I was interested in immunology and that was the place to study immunology in the 1980s,” he explains.
There, he began investigating the how the immune system clears the Hepatitis B virus. He selected a study cohort of homosexual men, as it was a population with an unusually high rate of chronic Hep B. Frazer discovered that the immune systems of significant number of the patients were unable to clear Hep B infections, and soon learned that similar cases of immune impairment in homosexual male populations were rapidly appearing elsewhere in the world. The condition became known as Acquired Immune Deficiency Syndrome (AIDS).
“I was amongst the first to confirm that AIDS was common in Australia, before a virus was associated with the disease, and to map out the natural history of the disease in Melbourne,” says Frazer.
A viral origin was suspected, so Frazer and his colleagues tested the immune-impaired cohort for a variety of viruses known to cause immune problems. None matched until they tested for a recently identified virus, HTLV-III. This virus later became known as HIV, and Frazer’s work contributed to the growing body of knowledge that identified HIV as the cause of AIDS.
Frazer and his colleagues were the first to notice that AIDS patients often had significant difficulty with genital warts, which are caused by human papilloma viruses (HPV). A recent hypothesis had proposed a connection between HPV and cervical cancer, so he searched for the presence of anogenital cancers and pre-cancers in these patients, and found a high prevalence. Frazer became convinced the immune system played a role in the ability to protect against HPV-linked cancer. His subsequent research showed that immunosuppressed patients couldn’t clear the virus and that the resulting, uncontrolled HPV infection led to cancer.
In 1985 Frazer moved to the University of Queensland to become a lecturer and Director of Immunology at the Princess Alexandra Hospital, where he went on to develop and direct the Centre for Immunology and Cancer Research (CICR). During this time, he established one of the first research groups in the world focussing on papilloma virus immunology. At the time it was thought HPV was rare and aggressive, but Frazer showed that it is extremely common, often latent, and that a subset of people develop detrimental chronic infections.
He wanted to learn how the immune system ‘sees’ HPV, particularly how it reacts to viral proteins as this could enable vaccine development. However, HPV proved impossible to grow in the lab. Frazer went on sabbatical to Cambridge University in the UK to search for a way around this significant problem. It was there he met the late Dr Jian Zhou, an expert in gene cloning who was also interested in HPV. They became good collaborators and good friends. Frazer invited Zhou to join his research group in Brisbane, where they embarked on a research project that was to make medical history. If HPV couldn’t be grown, they reasoned, then perhaps they could build their own version of the virus.
For a vaccine to work it must mimic the shape of the virus, as this is what the immune system recognises, so they cloned HPV surface proteins onto a different ‘template’ virus. After trial and error, Zhou figured out how to get the proteins to form precisely the right structure and the result was a ‘virus-like particle’. The GardasilTM vaccine was developed out of this discovery and is now in use in well over 120 countries primarily for the prevention of HPV-associated cervical cancer. Sadly, Dr Jian Zhou did not live to see the widespread use of the technology he had co-developed. He passed away unexpectedly in 1999.
Frazer continued the work that he and Zhou began, and in 2007 he founded and became Director of the UQ Diamantina Institute (UQDI), an amalgamation of the CICR and the UQ Centre for Diabetes and Endocrinology Research. He was Chief Executive Officer and Director of Research at the Translational Research Institute (TRI) Pty Ltd (2011 - 2014). He has received numerous awards for his contributions to immunology and cancer research, was elected as a Fellow of the Royal Society of London and received the Popular Prize from the European Patent Office 2015. He maintains a strong interest in ensuring his research benefits the global community and is actively involved in HPV epidemiology research and vaccination strategies in the developing world.
There are more than 20 million women already infected with HPV, for whom the existing vaccine cannot prevent cervical cancer. Moreover, cervical cancer is just one aspect of the total cancer burden caused by papilloma viruses, which include other genital cancers as well as throat cancers. Frazer believes these viruses are also responsible for certain types of skin cancer and is searching for evidence of the association.
He continues to lead his research group in the Epithelial Cancer Division at UQDI, focusing on the development of a therapeutic vaccine to treat those already infected with HPV. To this end, he wants to understand why the success of immunotherapy is extensively determined by the local environment around either the infection or the tumour. This microenvironment seems to have the ability to turn off the immune response, which presents a challenge to the development of immunotherapeutics. Overcoming that hurdle will have profound implications across a range of diseases.
Thus far Frazer and his colleagues have developed two promising new immunotherapies for HPV-associated cancers, which are currently in early stage trials. In his search for the immune on/off-switch, Frazer adds, “we have observed that local factors, particularly inflammation, determine whether vaccine-induced immune responses are locally effective against chronic virus infection and skin cancer.”
His innate curiosity certainly hasn’t abated, and when it comes to the immune system, Frazer intends to pull things apart to see how they work for a long time to come.
Email: Professor Ian Frazer
Telephone: +61 7 3443 8042
Dr Robert Tindle (Research Fellow 1987-1993). Now: Director of the Sir Albert Sakzewski Research Laboratories, Brisbane, Australia.
Dr Linda Selvey (PhD Student 1988-1991). Now: CEO of Greenpeace Australia.
Dr XiaoSong Liu (Research Officer 2001-2006). Now: Senior Lecturer in Immunology, The University of Newcastle.
Dr David Whitehead (Honours Student 1988). Now: Senior Research Fellow, Queensland Institute of Medical Research.
10 Recent Publications
Tran, Le Son, Mittal, Deepak, Mattarollo, Stephen R. and Frazer, Ian H. (2015) Interleukin-17A promotes arginase-1 production and 2,4-dinitrochlorobenzene-induced acute hyperinflammation in human papillomavirus E7 oncoprotein-expressing skin. Journal of Innate Immunity, 7 4: 392-404.
Abd Warif, Nor Malia, Stoitzner, Patrizia, Leggatt, Graham R., Mattarollo, Stephen R., Frazer, Ian H. and Hibma, Merilyn H. (2015) Langerhans Cell Homeostasis and Activation Is Altered in Hyperplastic Human Papillomavirus Type 16 E7 Expressing Epidermis. PLoS One, 10 5: e0127155-e0127155.
Jung, Ji-Won, Overgaard, Nana H., Burke, Michael T., Isbel, Nicole, Frazer, Ian H., Simpson, Fiona and Wells, James W. (2015) Does the nature of residual immune function explain the differential risk of non-melanoma skin cancer development in immunosuppressed organ transplant recipients?. International Journal of Cancer.
Bergot, Anne-Sophie, Monnet, Nastasia, Tran, Son Le, Mittal, Deepak, Al-Kouba, Jane, Steptoe, Raymond J., Grimbaldeston, Michele A., Frazer, Ian H. and Wells, James W. (2015) HPV16 E7 expression in skin induces TSLP secretion, type 2 ILC infiltration and atopic dermatitis-like lesions. Immunology and Cell Biology, 93 6: 540-547.
Apetoh, Lionel, Smyth, Mark J., Drake, Charles G., Abastado, Jean-Pierre, Apte, Ron N., Ayyoub, Maha, Blay, Jean-Yves, Bonneville, Marc, Butterfield, Lisa H., Caignard, Anne, Castelli, Chiara, Cavallo, Federica, Celis, Esteban, Chen, Lieping, Colombo, Mario P., Comin-Anduix, Begona, Coukos, Georges, Dhodapkar, Madhav V., Dranoff, Glenn, Frazer, Ian H., Fridman, Wolf-Herve, Gabrilovich, Dmitry I., Gilboa, Eli, Gnjatic, Sacha, Jaeger, Dirk, Kalinski, Pawel, Kaufman, Howard L., Kiessling, Rolf, Kirkwood, John, Knuth, Alexander, Liblau, Roland, Lotze, Michael T., Lugli, Enrico, Marincola, Francesco, Melero, Ignacio, Melief, Cornelis J., Mempel, Thorsten R., Mittendorf, Elizabeth A., Odun, Kunle, Overwijk, Willem W., Palucka, Anna Karolina, Parmiani, Giorgio, Ribas, Antoni, Romero, Pedro, Schreiber, Robert D., Schuler, Gerold, Srivastava, Pramod K., Tartour, Eric, Valmori, Danila, van der Burg, Sjoerd H., van der Bruggen, Pierre, van den Eynde, Benoit J., Wang, Ena, Zou, Weiping, Whiteside, Theresa L., Speiser, Daniel E., Pardoll, Drew M., Restifo, Nicholas P. and Anderson, Ana C. (2015) Consensus nomenclature for CD8(+) T cell phenotypes in cancer. Oncoimmunology, 4 4: . doi:10.1080/2162402X.2014.998538
McNeilly, Celia L., Crichton, Michael L., Primiero, Clare A., Frazer, Ian H., Roberts, Michael S. and Kendall, Mark A. F. (2014) Microprojection arrays to immunise at mucosal surfaces. Journal of Controlled Release, 196 252-260.
Velentzis, Louiza S., Sitas, Freddy, O'Connell, Dianne L., Darlington-Brown, Jessica, Egger, Sam, Sinha, Rohit, Banks, Emily, Frazer, Ian H. and Canfell, Karen (2014) Human papillomavirus 16/18 seroprevalence in unvaccinated women over 30 years with normal cytology and with high grade cervical abnormalities in Australia: results from an observational study. BMC Infectious Diseases, 14 3861: 1-10.
Gatica-Andrades, M. D., Nguyen, T. T. K., Schultz, T. E., Wyer, O. J. K., Melo-Bolivar, J., Walker, M. J., Frazer, I. H., Barnett, T. C. and Blumenthal, A. (2014). Interference with Wnt pathway improves host control of Listeria monocytogenes in vivo. In: Immunology. (112-112)
Freeman, Andrew, Bridge, Jennifer A., Maruthayanar, Pirashanthini, Overgaard, Nana H., Jung, Ji-Won, Simpson, Fiona, Prow, Tarl W., Soyer, H. Peter, Frazer, Ian H., Freeman, Michael and Wells, James W. (2014) Comparative Immune Phenotypic Analysis of Cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in Immune-Competent Individuals: Proportional Representation of CD8+ T-Cells but Not FoxP3+ Regulatory T-Cells Is Associated with Disease Stage. PLoS One, 9 10: e110928.1-e110928.9.
- Immunoregulation in skin and skin cancer
- Immunotherapy for HPV associated infections
- Novel approaches to immunisation.