Karnezis TG Awardee

A Room With A View:

 

A report on the 2010 Gordon Conference on the Molecular Mechanism of Lymphatic Function and Disease (Lucca, Italy)

Published with the permission of Dr. Tara Karnezis, Ph.D

 

In the early months of 2010, I was fortunate from two respects. First, my abstract was chosen to be presented at the prestigious Gordon Conference on the Molecular Mechanism of Lymphatic Function and Disease and second, I was awarded a coveted Cass Foundation travel fellowship to attend this event.

For an early career post-doctoral fellow that has ambitions to head an independent research team, a profile in his/her respective field is mandatory and attending Gordon conferences is a terrific opportunity to achieve this goal. The reason is that these series of conferences provide an international forum for the presentation and discussion of frontier research in the biological, chemical, and physical sciences. They are recognized as the world’s premier scientific conferences, where the leading investigators from around the world discuss their unpublished work and future challenges in a uniquely informal, interactive format and are generally held in the United States, Italy, China, and Switzerland.

Despite my 10 years of international travel, the prospect of swollen feet, waiting in transit ad finitum, jet lag and lost luggage still overwhelms me but I managed to arrive, nerves in check, at my destination with my over-packed suitcase and my poster still in tote. And what a destination….! Following check-in, I lugged both my luggage items- my suitcase of which had subsequently acquired ‘heavy’ labels- to my hotel room and when I swung open the wooden shutters, I felt like Miss Honeychurch in a scene from E.M Forster’s classic tale ‘A Room With A View’. This year, the meeting I was attending was held in Italy, with the vine-covered, rolling hills and sun-drenched terracotta roofs of Tuscany as the stunning backdrop to what proved to be a show case of cutting edge lymphatic biology research.

My area of medical research- and one I hope to make significant contributions in- is the biology of the lymphatic system; an intricate, hierarchically arranged network of vessels that is integral to interstitial fluid homeostasis, absorption of dietary fat and immune cell surveillance. The past few years have seen a surge of interest in the lymphatic system, largely due to the fact that lymphatic vessels can serve as conduits for tumour cell dissemination, thereby facilitating metastasis. Understanding the mechanism by which lymphatic vessels assimilate may provide avenues for rational drug design and effective therapies targeted towards pathological settings such as tumour metastasis and other types of lymphatic related pathologies such as lymphedema, the premise behind establishing a Gordon Conference some 8 years ago in this very exciting field of research.

The conference organisers, Michael Detmar (Swiss Federal Institute of Technology, Switzerland) and Guillermo Oliver (St. Jude Children’s Research Hospital, USA), put together a fantastic program that consisted of several themes: molecular mechanisms in lymphangiogenesis, lymphatic vessel morphogenesis and maturation, transcriptional regulation of lymphangiogenesis, signal transduction in lymphatic endothelium  and therapeutic targeting of the lymphatic vasculature. Perhaps the most prominent scientist in lymphatic biology research is Kari Alitalo (University of Helsinki, Finland) who delivered the plenary lecture. His numerous and extensive studies on how lymphatic vessels are regulated and the key pathways that may be targeted with inhibitory reagents was awe-inspiring. Other interesting talks were from Friedman Kiefer (Max-Planc-Institute, Munster) and Mark Kahn (University of Pennsylvania, USA) who presented their elegant and complementary studies on the important role of platelets, a vital cell of the immune system, in lymphatic vessel development.  The thought of cross-pollinating the giant field of immunology with the small and distinct field of lymphatic vessel biology intrigued me. These talks led me to postulate a research plan to examine the lymphatic architecture of mice with mutations in genes that regulated platelet production with collaborators in our very own Walter and Eliza Hall Institute (WEHI), something I am very much looking forward to pursuing.

The program itself was very intense: sessions started 8.30 am and often ran overtime beyond the 7.30 pm schedule. The lethargy felt towards the end of the day’s session was compensated by the knowledge that a pick-me-up of sumptuous Italian food and local wines was just about to be served. Dinner was often the best time to discuss the day’s sessions and pick the brains of the worlds experts in lymphatic research biology in relaxed surroundings. With the exception of some days, there were scheduled breaks in the afternoon which preceded poster viewing. These times allowed delegates to meet and mingle and sometimes sneak off to watch Germany defeat Australia (4/0) amongst other clashes in the FIFA World Cup. On a better afternoon, a small group of delegates decided to tackle the beaten track that led to the relatively nearby but charming city of Barga. During this trek, I was able to make the acquaintance of Stanley Rockson (Stanford University, USA), a clinician and pioneer in the field of lymphedema research. Lymphedema is the swelling that occurs when a dysfunctional lymphatic system prevents the lymph fluid in the arm or leg from draining adequately. As the fluid accumulates, the swelling continues. It commonly occurs following surgery for cancer and is an ongoing challenge for the patient, not only from an aesthetic view point but more importantly, the medical complications that arise as a consequence. Professor Rockson presented a lecture on the development of a lymphedema patient repository that would allow researches access to patient tissue. Speaking with Professor Rockson, we thought it would be a good idea to develop a mouse repository that would make available all strains of mice known to carry genetic mutations that cause a dysfunctional lymphatic system to the global lymphangiogenesis research community. Professor Rockson turned out to be a wonderful mentor and advised me on how to compete in a very competitive field

My turn for peer review, critique, scrutiny and judgment was scheduled for the day before my birthday. My poster presentation was up and on display and I was on stand-by ready for the attack. I was not at all prepared for the continual and constant crowd of very interested colleagues who had very nice things to say about my work! In a nutshell, what I had shown is that there is a merging of two major signalling pathways in lymphatic endothelial cells that help regulate the tone or shape of lymphatic vessels, an aspect of lymphatic vessel function that can be manipulated pharmacologically to help reduce the spread of cancer cells to other sites in the body. The major critique I received was “When is this work going to be published?!” Soon I promised them. With that behind me, I was able to enjoy the remainder of the conference, my birthday complete with song and cake and the finale of Disco night which was a tribute to what felt like Eurovision, where inhibitions of what people think of ones dance moves go flying out the window and pictures really do tell a thousand words.

On the long haul back to Melbourne, I reflected on the inspirational people I met and interacted with, the collaborative projects that were initiated and the amazing science I had the privilege to listen to delivered by the world leaders in the field. I was able to convey all the findings back to my lab colleagues and supervisors, the knowledge of which facilitated our own research agendas and in some cases re-directed current research activities. With this, I extend my utmost gratitude to the Cass Foundation for enabling me to attend what turned out to be a brilliant meeting and a stepping stone to a bigger and better career.