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Interview with Dr Barbara Guinn

Posted Mon, Jun, 08,2009

This interview is with Dr Barbara Guinn , Editor in Chief of Biomarkers in Cancer , a new open access journal published by Libertas Academica.

Dr Guinn is a Senior Research Fellow at The University of Southampton and a visiting scientist at King’s College London. She is also Associate Editor of Immunotherapy Insights and was Associate Editor of Biomarker Insights until we began work on Biomarkers in Cancer .

Tom: What would you say is the primary focus of your research effort (and how do you refer to your 'sub-area')?

My main research effort has been identifying targets for the immunotherapy of myeloid leukaemias. We have been using SEREX, microarray and RT-PCR to identify antigens which may be used for the immunotherapy of acute myeloid leukaemia. In the past 2.5 years I have been working at the University of Southampton, using Freda Stevenson’s pDOM-epitope DNA vaccines in transgenic HLA-A2 mice, as a pre-clinical model for the immunotherapy of acute myeloid leukaemia (AML) and incorporating some of our most promising A2 restricted epitopes into Freda’s vaccine design.

Tom: What do you consider to be the most significant developments arising from research in your area?

We have identified a number of antigens which would be suitable targets for the immunotherapy of AML as well as other solid and haematological malignancies. For instance we identified the novel cancer-testis (CT) antigen, PASD1, as the most frequently expressed CT antigen in AML, and more recently we identified a modified PASD1 epitope which can induce immune responses against processed and presented wild type PASD1 in leukaemia and solid tumour cells. In addition we have identified SSX2IP as a marker of prognosis in AML as well as a possible target for immunotherapy.

Tom: What do you consider to be the most significant open questions and research challenges in your area?

I think we still need to determine which technique(s) will provide the most effective delivery of immunotherapy to patients, and how and when these should be applied. The answer will vary between disease groups and sub-groups as well as between individual patients. Like many others in the field I suspect a combination of immunotherapy strategies and the targeting of a number of disease-specific parameters will be the future of immunotherapy. Of course how we will determine the appropriate patient-specific treatment remains undecided although techniques such as microarray offer the most obvious promise at the moment.

Tom: Tell us about your collaborative research. Who else do you directly work with and what are the aims of your collaboration?

I work with Drs Karen Pulford and Alison Banham at the University of Oxford on PASD1. We hope to further confirm its potential as an immunotherapeutic target in solid tumours. I work with Professor Hans-Georg Rammensee and Dr Dagmar Sigurdardottir (University of Tubingen, Germany), who provide pMHC monomers for the tetramer arrays we have been optimising. We are analyzing patient samples pre- and post-treatment (conventional and immunotherapy) to show how T cell populations wax and wane against viral and tumour antigen epitopes with treatment. This may affect what immunotherapy treatments these patients receive in the future in personalized clinical trials. We receive samples for these studies from Dr Kim Orchard (University of Southampton) and Professor Jochen Greiner (University of Ulm, Germany).

I have had a very long standing collaboration with Professor Ken Mills, who was also one of my PhD supervisors and is now at Queen’s University, Belfast. We have been examining the expression of leukaemia antigens such as RAGE-1, MGEA6 and SSX2IP in AML. We have shown that SSX2IP is associated with SURVIVIN and RHAMM, and individually and together these leukaemia antigens provide markers of survival for AML patients at disease presentation. We increased our patient numbers through collaborations with Professor Jochen Greiner and Dr Lars Bullinger (University of Ulm) and we continue to collaborate with these groups to investigate whether other leukaemia antigens may also provide survival markers in AML.

In addition I collaborate with Dr Stephanie McArdle (Nottingham Trent University) on HAGE, which we identified as a CT antigen expressed in 54% of chronic myeloid leukaemia patients.

Tom: Is balancing all these activities challenging? How do you deal with it and what tools do you find useful in doing so?

It is sometimes stressful close to grant deadlines, especially as a lot of other work has to go on hold on the more intense days. I still do some lab work as well as running my own (albeit small) group. I keep lists and find my mobile office (a very portable laptop) and Blackberry essential. Of course the internet, Pub-Med and EndNote have made life a lot easier. We are all becoming masters of numerous arts, data analyses, preparing figures, writing papers and performing a wider range of techniques in the lab. These things we take for granted but the web is only 20 years old (this year) and I paid a secretary to type up my B.Sc. thesis in 1991, so the way we work and what we expect to achieve has changed dramatically, even in just the last twenty years.

Tom: When did you decide to be primarily involved in the field that you are now in?

I did my B.Sc. in Genetics before the field became popular. I was advised against it at High School as I was told it was too specialized. There were four people on my degree course in my first year (1988) and only two in the second year. I was lucky that it worked out and Genetics became so relevant to cancer research. I guess I always wanted to be in the medical sciences and remember telling relatives I wanted to be a doctor from the age of eight.

Tom: What resources do you find indispensible for your research work?

Email and the internet. It allows me to talk to collaborators and research what is already publically available in my areas of interest quickly. Meetings allow the rapid dissemination of information and networking which has helped me meet collaborators and friends. I have also been lucky to have and have had a number of very keen and dedicated staff. I try to make work a fun place and minimize the pressure people can feel to perform.

Tom: What do you think about the development of open access publishing and open access development? How has it changed your perspective on research or development practices?

Open access publishing and open access development has allowed the easy (free) access of manuscripts. It has also expanded the type of manuscript I can access and that has broadened my horizons and changed the research I can and will read.

Tom: What books do you think should be required reading for researchers working in your area?

"Essential Haematology" edited by A.V. Hoffbrand and J.E. Pettit and published by Blackwell Scientific Publications. [ Amazon ] "Cellular and Molecular Immunology" edited by A.K. Abbas, A.H. Lichtman and J.S. Pober and published by Saunders [ Amazon ], and "Immunobiology", Edited by C.A. Janeway, P. Travers, M. Walport and M.J. Shlomchik. [ Amazon ]

Tom: What books are current on your reading list?

I am looking forward to reading "Epitope Mapping Protocols" edited by G.E. Morris and published by Humana Press [ Amazon ] and have just read "Gene Therapy Immunology" edited by R. Herzog and published by Wiley-Blackwell. [ Amazon ] It was about the unwanted immune responses which are caused by gene therapy and so was different from immunotherapy where we try to induce immune reactions to kill tumour cells.

Tom: Do you teach any courses? If so, which ones?

No, not at the moment. I work on a hospital site so there aren’t many courses pure scientists can teach medical students.

Tom: Which historical research figures do you think have most influenced you in how you think about research? Why are they significant?

Isaac Newton makes me smile. He was young and smart and just pipped other researchers to the post. Marie Curie because she was so dedicated. James Watson, Francis Crick and Rosalind Franklin for determining the structure of DNA, and Gregor Mendel “the father of modern genetics” for determining how inheritance occurred in pea plants.

Tom: Which meetings do you attend on a regular basis?

I enjoy the International Society for the Cell and Gene Therapy of Cancer annual meeting, to be held in Cork from 2nd – 4th September 2009, and this year I will go to the Progress in Vaccination Against Cancer 2009 to be held in Sofia, Bulgaria from the 8th -10th October 2009. The British Society for Haematology , the American Association for Cancer Research and the American Society for Hematology . Annual Meetings are all regular features in my work calendar, and I’d highly recommend the Cancer Research Institute’s Cancer Vaccine meeting .

Tom: If you could change something about how research in your area is conducted, used, perceived, or resourced, what would it be?

I spend a lot of time writing grants and trying to renew funding. I can’t see how else people could be independently assessed and the best grants funded, but if the system could be changed and improved, that would be great. Perhaps more grant funding, more fellowships, and more University funded permanent posts which would help us concentrate on the lab work and less time trying to secure money.

My thanks to Dr Guinn.


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