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Report of the 42nd annual ISEH conference - a new investigator perspective

Posted By Connections Editor, Friday, November 01, 2013
Updated: Thursday, October 24, 2013

Contributed by Courteney Lai (pictured, below left) Graduate Student, BC Cancer Agency, Vancouver, BC and Dr. Joanna Wegrzyn, (pictured below right) postdoctoral fellow BC Cancer Agency, Vancouver, BC.

The Art of Science in Vienna

Vienna, the capital of Austria, is known as a cultural epicenter of Europe; a city which seamlessly weaves its historical, artistic, and scientific past with the modern world of technology and urban life. Vienna is well known in many cultural circles: as the City of Music, due to its rich legacy as a leading music centre; the City of Dreams, as home to the first psycho-analyst, Sigmund Freud, and for its rich architectural history that embraces its Roman roots, Gothic and Baroque influences, and modern architecture.

It was in this exciting city where storied history met the latest trends that the 42nd annual scientific meeting of the International Society for Hematology and Stem Cells (ISEH) convened from August 22-25, 2013. Presided over by the Society's President Elaine Dzierzak and the Chair of the Scientific Committee Margaret Goodell, the meeting had an attendance of 380, composed of a truly international contingent with representatives from all continents, of which over 45% were new investigators. Over the 5 days, three key themes emerged: (i) understanding fate decisions and lineage development, and the role of stem cell niche in these processes (ii) the continued role of epigenetics, and (iii) the role of new technologies from the discovery stage to sequencing and personalised medicine. Much like the way Vienna has been compared to a unique onion, with each facet and neighbourhood representing layers that contribute equally to the overall flavour of the city, each of the meeting’s themes emerged as equally important to the study and understanding of hematopoiesis and stem cells.

A journey through art and science in the zebrafish

This year’s Donald Metcalf Lecture was given by Dr. Leonard Zon, Grousbeck Professor of Pediatrics at Harvard University, and formed the prelude to the meeting. Dr. Zon took a look back and gave an outstanding presentation modeled on the different stages of his career. This great lecture was composed of a mixture of recent scientific findings from the Zon laboratory, interludes of his own music performances (he has played first trumpet in the Longwood Symphony for 30 years!), and outlined by a series of Thomas Cole paintings entitled The Voyage of Life.

As an introduction to this wonderful talk, we were treated to a /video showing hematopoietic stem cell (HSC) induction and migration in zebrafish for the first time. The Zon laboratory uses zebrafish as a model organism to uncover mechanisms and pathways responsible for generating adult blood stem cells. Dr. Zon also shared his fantastic discovery from a chemical screen in zebrafish, which revealed a very important role for PGE2 as a stimulator of blood cell engraftment and which is currently being tested in clinical trial to improve blood cell transplantation in leukemic patients. This was a great reminder for most of us, basic scientists, about the continued relevance of basic science in translation to clinic.

Dr. Zon concluded his talk about the journey of HSCs through subsequent sites of hematopoiesis with a great analogy, comparing the developmental stages of stem cells with research career paths, where the AGM reflects high school, fetal liver, college, and finally the bone marrow as graduate school, with each stage containing a full set of factors that influence the future steps. We really hope for more meetings like this, which for most of us trainees, are definitely key factors regulating our future fate decisions.

In summary, the Metcalf lecture not only set the stage for the main message of this meeting – the importance of developing new leukemia treatments – but also highlighted its great location: Vienna, the city of world-class music and, for the next five days at least, world-class science.

Mechanisms of HSC fate decision

Contrary to initial hypotheses, there has been increasing evidence that not all HSCs are created equal. Rather, many continue to probe the heterogeneity existing in the HSC compartment, and the consequences of this heterogeneity on differentiation into different cell types. These issues were crystallised during Camilla Forsberg’s presentation on the mechanisms of HSC fate decisions, where she utilised her lab’s Flk-Switch lineage tracing model and known Flk2 status of each stem and progenitor cell population to track lineage differentiation and the heterogeneity capabilities of multi-potent progenitors (MPPs). Similarly, Shalin Naik used cellular barcoding to illustrate that true multipotent progenitors contribute very little to the overall immune reconstitution of animals, but rather, progenitors inherit the lineage biases of their parent cells, and it is these cells that dominate the system. David Bryder also addressed the question of fate decision in malignant hematopoiesis, through lineage tracing in MLL-ENL leukemia. Using a tet-inducible MLL-ENL model, the Bryder group quantified colony formation and in vivo reconstitution ability from different sub-populations of cells, illustrating a hierarchy of leukemia competence. Here, the idea emerged that cells were previously capable of multi-lineage competence, but ‘de-differentiate’ to have preferred differentiation pathways with functional consequences.

The HSC balancing act is influenced by epigenetic factors

Once again, epigenetics and understanding epigenetic regulation in the context of normal and malignant disease remained a key theme of the meeting. Gerald de Haan reminded everyone that understanding HSC self-renewal can be viewed on a continuum of homeostasis. Normal HSCs exist balanced between hyperproliferation and bone marrow failure. Perturbation towards hyperproliferation can quickly lead to myeloproliferation and leukemia, while a push towards the other direction can result in impaired immune function, tissue degeneration, and bone marrow failure. This served as an excellent prelude to his studies on the factors affecting differentiation and self-renewal of HSCs, in which he investigated the differential effects of overexpressing PRC1 components – specifically Cbx 2, Cbx4, Cbx7, and Cbx8 – on HSC activity. Marnie Blewitt delved further into epigenetic regulation, proposing a hierarchical model of PRC action, with depletion of PRC2 components enhancing HSC function, but depletion of PRC1 or YY1 impairing HSC function, and evidence that specific epigenetic factors may play different roles in fetal versus adult cells. Grant Challen moved the talks towards DNA methylation by discussing the roles de novo DNA methylation plays in HSC activity, as well as the individual and combined effects of Dnmt3a and Dnmt3b on DNA methylation, self-renewal, and differentiation.

The role of new technologies: from sequencing pipelines through new mouse models to patient's bedside

A common thread through presentations was that there is a genuine need for new treatment strategies for leukemia. The big hope for the development of new drug treatments as well as improving current methods of stem cell transplantation lies in bridging the gap between basic science and the clinic, and bringing together scientists working on different systems. The other key part lies in translating into the clinic findings delivered from wide range of new technologies such as high throughput screens, including genome and epigenome sequencing, followed by targeted validation with the use of knock-in/out mice. This year at ISEH, we saw a few examples, in which big findings from sequencing of T-ALL, AML and MDS patient samples resulted in the development of new mouse models of these diseases or improved prognostication for patients with AML, MDS and MPD. Jan Cools reported new mutations in Jak3 as well as mutations in ribosomal proteins that differentiate between pediatric and adult cases of T-ALL, while Ross Levine shared work linking clonal hematopoiesis with known epigenetic modifiers Tet2 and ASXL1. It was also quite reassuring to hear Ross Levine, a pioneer in development of personalized medicine programs, state that some of the major findings gained from sequencing will be utilized in the clinic this year. Other interesting technologies such as RNAi screens and in vivo imaging of live transplanted mouse hematopoietic stem/progenitor cells (HSPCs) were used to dissect questions regarding the role of niche for HSC engraftment and function.

A trainee-focused meeting

As trainees, what makes this meeting so unique is the concentrated focus on providing opportunities for and promoting trainees. From showcasing selected abstracts from PhD and postdoctoral fellows in oral presentations, to the award of the best oral presentations by a young investigator and to even vendor booths targeted specifically towards trainees, ISEH continues to place emphasis on trainees and supporting trainee development. This trainee-centred theme was most notable in the New Investigator track, which consisted of a variety of trainee-oriented events throughout each day of the conference. Trainees attended the Effective Networking session at lunch, where Louise Purton, Toshio Kitamura, and Leonard Zon stressed the importance of selling oneself and building connections in science. Trainees were able to practice and hone their elevator pitches at the Midsummer Night Mixer that evening, networking with many of the scientists over the ISEH people bingo icebreaker, at the Meet the Experts lunch the following day, where many scientists volunteered their time to impart career advice to the up-and-coming new investigators, and at the annual ISEH social that evening. The final New Investigators career panel, Effectively Presenting Yourself and Your Science, focused on presentation skills and managing one’s online image. Peggy Goodell gave excellent advice on preparing a successful Powerpoint presentation, while trainees Peter van Galen and Eugenia Flores-Figueroa focused on the importance of using social media such as Twitter, Facebook, and LinkedIn, effectively, as well as stressing the importance of proper etiquette in the digital world.

Wild and trained horse gaits: a close relationship

This year’s McCulloch and Till Award Lecture was delivered by Dr. Hanna Mikkola, who gave a fascinating talk about uncovering the roadmaps to the successful generation of hematopoietic stem cells. Dr. Mikkola presented her recent outstanding work on the role of different gene regulatory networks in specification of embryonic endothelium into hematopoietic cells. Throughout her lecture, Dr. Mikkola also shared her passion for horses. Indeed, one can see an analogy between hemogenic endothelium stem cell fate and horse gaits. There are various ways a horse can move: naturally or as a result of specialized training by humans, as seen in the famous Vienna Spanish Riding School. However, the latter would not exist without the former. Similarly, advancing our knowledge about those key signals necessary for normal embryonic/fetal hematopoiesis is essential to the process of generating true hematopoietic stem cells from pluripotent stem cells.

Advice to the trainees

Both 2013 ISEH keynote talks by Dr. Mikkola and Dr. Zon taught us about the beauty of the HSC developmental journey and the role different niches play in this process. However, there were also a few other messages for all new investigators and trainees from both of these great scientists. Similar to the importance of the niche in the development process, all of the education we have received, from childhood to our current attendance at meetings like ISEH, are critical for our future career development. Both of those speeches also emphasized the importance of balance in our lives. Our passion for science should be complemented by having a healthy outside life which, according to Dr. Zon, keeps you "grounded" and it is very helpful for a "productive life". Additionally, Dr. Mikkola stressed that we should not be scared of risks, as taking risks will yield the greatest rewards. As final words of encouragement, so critical to young investigators, Dr Mikkola added that good scientists never give up: "We all fall; it is just matter of who keeps standing back up".

On behalf of all trainees and attendees of the 42nd annual ISEH conference, we would like to extend our sincere thanks to Elaine Dzierzak, Margaret Goodell, and the rest of the organizing team for a very well executed conference. We look forward to meeting our fellow colleagues and researchers again next year in Montreal!

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