Dr Kylie Mason
Walter and Eliza Hall Institute of Medical Research/Royal Melbourne Hospital, Melbourne, Australia
Dr Kylie Mason has set herself the goal of developing new ways of treating diseases that are considered incurable.
Working as a clinician and scientist she is pioneering new treatments for blood cancers, some of which are already being clinically trialled in Melbourne.
Fifty years ago the chances of surviving leukaemia and other blood cancers were low. Today your chances are much better. But the treatments take a long time and have significant side effects. And some adult blood cancers are still very difficult to treat.
Kylie’s research has opened up new options that build on our understanding of why cancer cells ‘forget to die’. Her work has also suggested a way to extend the life of platelets, the cell fragments that manage blood clotting.
With her L’Oréal For Women in Science Fellowship, Kylie will look at ways to reduce the side-effects of the new drugs, and also to explore the role of platelets in cancer.
As a teenager Kylie Mason survived leukaemia. That experience fired her interest in medicine and, in due course, she qualified as a doctor and trained as a blood specialist.
“Training at the Royal Melbourne Hospital and at the Austin Hospital I spent a lot of time looking after patients with various blood cancers,” she says. “While we could successfully treat most of the children, helping adults was harder. About half of the adults with acute leukaemia still die of their disease.”
So she turned to research and the challenge of developing new treatments by doing a PhD at the Walter and Eliza Hall Institute for Medical Research. It was a perfect fit, not least because of the Institute’s rich history in understanding and fighting cancer.
In the 1980s Professor Don Metcalf transformed cancer therapy with his discovery of the colony stimulating factors (CSF) that tell stem cells when to grow and create white blood cells. Stem cells are designed to keep growing and producing replacement cells around the body. Most cells are not. They have a predetermined self-destruct time. If they ‘forget to die’ they can become cancerous.
Dr David Vaux and colleagues, also at the Institute, then discovered a gene called BCL-2 that promotes survival of a cell. We now know that some proteins in the Bcl-2 family promote cell survival while others promote cell death, and that there’s a balance in every cell between the two.
This discovery opened new opportunities for cancer treatment that companies around world have leaped at. One of them, Abbott Laboratories, has created drugs that target the pro-survival proteins, and has brought them to Melbourne for trials.
An important challenge for any new cancer drug is that it needs to stop the fast-growing cancer cells without causing too much damage to healthy stem cells that need to grow rapidly to replenish our immune cells.
During her PhD, Kylie and colleagues showed that one of Abbott’s potential drugs (ABT-737) would not work if the cancer cells were producing large amounts of a pro-survival protein. This study, which has now been cited over 400 times, suggested that combination therapies would have more chance of success.
So Kylie explored some of the options and showed that the drug worked well against aggressive leukaemias in mice if used in combination with low doses of standard chemotherapy drugs. This work has led to several clinical trials in Melbourne and elsewhere.
Longer lived blood products
In the course of her work Kylie also explored the side-effects of the drug and found that it kills platelets in the blood, but it doesn’t affect their production in the stem cells in our bone marrow.
Platelets are involved in blood clotting. Cancer patients often require transfusions of platelets, but supply is a challenge for blood banks as they only keep for five days. Kylie’s work suggested that platelets have a molecular clock and that the Bcl proteins are involved. This work will not only help cancer patients, it may open the way to extend the blood bank life of platelets and to a better understanding of diseases that affect platelets.
Kylie will use her L’Oréal Australia and New Zealand For Women in Science Fellowship to understand better some of the side-effects of the new drugs, and to explore the relationship between platelets and cancer development. She will also use her grant to travel to an international conference.
“Kylie’s personal journey battling cancer over many years has not only fuelled her passion for medicine and research, but provides her with an almost unique perspective: cancer patient; haematologist; scientist; and mother,” says Dr Doug Hilton, the Director of the Walter and Eliza Hall Institute.
“I am fortunate to be able to be a bridge between research at the Institute and the clinic at the Royal Melbourne Hopspital,” says Kylie. “This enables me to facilitate communication and act as a mentor, particularly for junior doctors keen to pursue a role in basic research.”
“I hope my work will make a difference firstly to patients with leukaemia. In the long term I hope it will also contribute to the fight against other hard-to-treat cancers such as lung and bowel cancer,” says Kylie.
2007 – PhD (Medical biology), The University of Melbourne/Walter & Eliza Hall Institute of Medical Research
1996 – Bachelor of Medicine and Bachelor of Surgery, The University of Melbourne
Career highlights, awards, fellowships, grants
2011 – present Honorary Fellow, Department of Medical Biology, The University of Melbourne
2007 – present Victorian Cancer Agency Clinician Fellow, Walter and Eliza Hall Institute of Medical Research
2007 – present Clinical teacher, The University of Melbourne (Royal Melbourne Hospital Clinical School)
2005 – present Consultant Haematologist, Department of Clinical Haematology and Bone Marrow Transplantation, Royal Melbourne Hospital
2012 – Melbourne Health Home Lottery Research Award, “Dependence of Haematological malignancy on pro-survival proteins”
2012 – Leukaemia Foundation of Australia Grant -in-Aid, “Evaluating the efficacy and tolerability of targeting pro-survival Mcl-1 in vivo”
2011 – 2012 Victorian Cancer Agency Clinician Fellowship
2010 – Leukaemia Foundation of Australia Research Grant -in-Aid, “Promoting cell death to improve treatment of Chronic Lymphocytic Leukaemia”
2009 – Premier’s Award for Health and Medical Research, Victorian State Government
2009 – Named in ‘Melbourne’s Top 100 Most Influential People’ – The Age Newspaper
2009 – Specialist Certificate in Clinical Research (Oncology) First Class Honours, The University of Melbourne
2008 – Young Tall Poppy Science Award, Victorian State Government
2007–2010 – Clinician Researcher Fellowship in Cancer, Victorian State Government
2006-2011 – Leukemia & Lymphoma Society of America Specialized Center of Research Grant, “Apoptosis in hematopoesis, leukemogenesis and therapy”
2006 – Cleveland Young Investigator’s Award, Royal Melbourne Hospital
2006 – Albert Baikie Memorial Medal, Haematology Society Australia & New Zealand
2005–2007 – PhD Candidate, Walter and Eliza Hall Institute
2005–2006 – Sessional Consultant Haematologist, Sunshine Hospital
2004 – Fellow, Royal College of Pathologists of Australasia
2004 – Fellow, Royal Australasian College of Physicians
2001-2006 – Leukemia & Lymphoma Society of America Specialized Center of Research Grant, “Mechanism of Bcl-2 pro-survival function”
2001–2004 – Advanced training in Haematology (Clinical and Laboratory), Royal Melbourne and Austin Hospitals
1997–2000 – Basic Physician training, Austin Hospital
Top five publications
van Delft M.*, Wei A.*, Mason K.D., Vandenberg C.J., Chen L., Czabotar P.E., Willis S., Scott C.L., Day C., Cory S., Adams J., Roberts A.W., Huang D.C.S. (2006) The Bh2 mimetic ABT-737 targets selective Bcl 2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized, Cancer Cell 10(5):389-399. * Joint first author (Impact factor 18.7, 404 citations)
Mason K.D., Carpinelli M., Fletcher J., Collinge J., Hilton A., Ellis S., Kelly P., Ekert P., Metcalf D., Roberts A.W., Huang D.C.S., Kile B.T. (2007) Programmed nuclear cell death delimits platelet life span, Cell 128:1173-1186. (Impact Factor 29.4, 193 citations)
Mason K.D., Vandenberg, C.J., Scott, C.L., Wei, A.H., Cory, S., Huang, D.C.S, Roberts, A. (2008) In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas, PNAS 105(46):17961-6. (Impact factor 9.6, 42 citations)
Mason K.D., Khaw S.L., Rayeroux K.C., Chew E., Lee E.F., Fairlie D., Grigg A.P., Seymour J.F., Szer J., Huang D.C.S., Roberts A.W. (2009) The Bh2 mimetic compound ABT-737 Synergizes with a Range of Cytotoxic Chemotherapy Agents in Chronic Lymphocytic Leukemia, Leukemia 23(11):2034-41. (Impact factor 8.6, 25 citations)
Schoenwalder S.M., Yuan Y., Josefsson E.C., White M.J., Yao Y., Mason K.D., O’Reilly L.A., Henley K.J., Ono A., Hsiao S., Wilcox A., Roberts A.W., Huang D.C., Salem H.H., Kile B.T., Jackson S.P. (2009) Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function, Blood 114(3):663-6. (Impact factor 10.9, 54 citations).
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