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Recap of the 2016 ISEH Annual Meeting in San Diego

Posted By Connections Editor, Friday, October 21, 2016

ISEH Connections: Recap of the 2016 ISEH Annual Meeting in San Diego

Novella Guidi, Daniel Lucas, Sofie Singbrant-Söderberg, Cédric Tremblay and Stephen Sykes

 

Now that this year’sl International Society forExperimental Hematology (ISEH) Annual Scientific Meeting – held in sunny San Diego, California – has come to a close, we here at the New Investigator’s Committee (NIC) wanted to recap and review some of the highlights, special sessions and the emerging scientific themes of the meeting.

 

The 1st Annual Pre-meeting workshop

2016 was also the first instance of the ISEH Pre-meeting Workshop. The workshop focused on providing career advice and networking in a more informal setting for graduate students and postdocs. The Pre-meeting was organized by Dr. James Palis and trainees were mentored by senior ISEH faculty. The workshop consisted of two career development talks, student presentations and a poster session. In the first career development talk, Dr. Michael Milsom gave a lecture on “How to Give a Good Talk”. In the second talk, Dr. Nancy Speck provided a retrospective of her own career, the decisions that she made that helped or hindered it, the pitfalls to avoid, and the critical milestones necessary to build a successful career in academia.  

 

The senior ISEH faculty also selected two trainee talks for presentation at the main meeting in the “Therapeutic Manipulation” session. The first one was by Mathew Angelos from Dr. Dan Kaufman’s lab where he presented his work demonstrating that inhibition of Aryl Hydrocarbon receptor can be used to greatly increase the differentiation of human embryonic stem cells into CD34+CD45+ hematopoietic progenitors. The second was by Marta Derecka from Dr. Rudolf Grosschedl’s lab presenting her discovery that the transcription factor Ebf1 functions in mesenchymal progenitor to maintain their ability to support HSC.

 

The Donald Metcalf Award: Thalia Papayannopoulou (University of Washington, US)

This year’s recipient of the Donald Metcalf Award – presented to distinguished scientists in hematology research – was Dr. Thalia Papayannopoulou. Dr. Papayannopoulou’s historic career as an experimental hematologist has transcended 6 decades and had yielded numerous seminal observations that have helped shape our view of the hematopoietic system. Her extensive research portfolio extends to many facets of hematopoiesis and erythropoiesis, from her role in defining how integrins contribute to hematopoietic stem and progenitor cell (HSPC) biology to her discoveries regarding globin regulation and switching – just to name a few. Her research has enlightened so many in the scientific community and so we say thank you and congratulations to Dr. Papayannopoulou.

 

Emerging & Continuing Themes in Experimental Hematopoiesis

            The conclusion of Dr. Papayannopoulou’s lecture marked the opening of a festival of exceptional invited speakers and short oral presentations. With over 60 scheduled oral presentations, we observed many new and continuing themes emerging throughout the meeting. In the session (Hematopoiesis I) immediately following the Donald Metcalf Award, Emmanuelle Passagué (University of California at San Francisco (UCSF), US) presented work describing the importance of metabolic switching and autophagy in hematopoietic stem cell (HSC) activation, differentiation and return to quiescence. This presentation was complemented by that of Danica Chen (University of California at Berkeley, US) in the Californian Sampler session, who discussed the roles of the mitochondrial unfolded protein and the mitochondrial oxidative stress responses in HSC activation, quiescence and aging.

 

Mick Milsom (Heidelberg Institute for Stem Cell Technology and Experimental Medicine, DE), who also spoke Hematopoiesis I, presented data showing the impact of inflammatory stress on HSC biology. The role of inflammatory cytokines in HSC biology was also the showcase of talks by Katherine King (Baylor College of Medicine, US), Eric Pietras (University of Colorado at Denver, US) and Masayuki Yamashita (UCSF, US).

 

The continuing trends of HSC aging and the role of the HSC niche were also on display at this year’s meeting. Specifically, talks by Kateri Ann Moore (Mount Sinai, US), Stavroula Kousteni (Columbia University, USA) and Novella Guidi (Ulm University, DE) provided new insights about how HSCs age. And, in a titan-filled session entitled “Niche”, John Chute (University of California at Los Angeles, US) discussed how niche-derived factors influence both normal and malignant hematopoiesis. In the same session, Paul Frenette (Albert Einstein College of Medicine, US) spoke of the role of a specialized Nestin+ niche population in developmental hematopoiesis and Sean Morrison (University of Texas Southwestern Medical Center, US) used specialized transgenic mice to introduce adipocytes as a niche component that support HSC biology following irradiation.

 

Several technological advancements were also on display at the 45th annual ISEH meeting. For example, the use of single cell sequencing techniques to address complex hematological and non-hematological questions was a common theme amongst the talks of Lee Grimes (Cincinnati Children’s Hospital Medical Center, US), Peter Lansdorp (BC Cancer Research Centre, CA), Claus Nerlov (University of Oxford, UK) and Fan Zhou (Academy of Military Medical Sciences, CN) as well as the topic of the New Investigators Career Session (discussed below). Konstantinos Kokkaliaris (ETH Zurich, CH) presented a new method for three-dimensional multicolor quantitative imaging of bone marrow niches and François Mercier (Massachusetts General Hospital, US) described the development of a new congenic mouse model for hematological research.

 

In addition to the many fantastic talks on the regulatory mechanisms governing normal HSPC biology, there were also numerous talks focused on malignant hematopoiesis. In particular, Ulrich Steidl (Albert Einstein College of Medicine, US) presented exciting data showing the role of PU.1 in leukemogenesis as well as a novel strategy for pharmacologically targeting PU.1 in myeloid malignancy. Guy Sauvageau (Institute for Research in Immunology and Cancer (IRIC), CA) presented data from the Leucegene project, which aims to identify novel, effective chemotherapies for treating acute myeloid leukemia (AML) by combining RNA-seq data from a large cohort of AML patients with chemo-genomic screens. Irene Baccelli (IRIC, CA) presented the results of a targeted chemical compound screen where specific bioinformatic approaches were applied to identify drug combinations that work in synergy across different sub-types of AML. Several other talks also provided new mechanistic insights with therapeutic implications in hematological malignancies. Specifically, Henny Maat (University Medical Center Groningen, NL) and Anne-Katrine Frank (University of Copenhagen, DK) showed that the Polycomb proteins, USP27 and JARID2, respectively are potential therapeutic targets in leukemia. Sal Lee Goh (MRI-UQ, AU) showed evidence that pharmacological blockade of macrophage colony stimulating factor (CSF-1) may be another possible therapeutic strategy in AML.

 

The role and potential targeting of epigenetic enzymes in hematological malignancies was discussed in multiple talks. Mark Dawson (Peter MacCallum Cancer Centre, AU) discussed epigenetic therapies currently in early stage clinical trials and also presented a fascinating chemical strategy for tracing the cellular penetration of epigenetic therapies in cells and in vivo. Warren Pear (University of Pennsylvania, US) provided insights on how specialized domains within super-enhancers dictate drug resistance in T-cell acute lymphoblastic leukemia (T-ALL). Grant Challen utilized mouse models to show that deletion of Dnmt3a – mutated in ~20% of T-cell malignancies – leads to defects in normal T-cell development and allows progenitors to become more susceptible to NOTCH1-induced T-ALL. Additionally, Patricia Ernst presented data that selectively targeting just endogenous MLL1 in MLL-rearranged leukemia may be ineffective due to the actions of MLL2.

 

In the realm of myeloid neoplasms and pre-malignant syndromes, Radek Skoda (University Hospital Basel, CH) and Goro Sashida (Kumamoto University, JP) both used sophisticated mouse models to identify the cooperative molecular effects that result from compound genetic mutations that are commonly found in myeloproliferative neoplasms (MPNs).

Additionally, Rafael Bejar (University of California at San Diego, US), Teresa Bowman (Albert Einstein College of Medicine, US) and Carl Walkley (St. Vincent Institute, AU) presented data showing the cellular and molecular consequences of spliceosome mutations – commonly found in MDS and AML patients – on both healthy and malignant HSCs.

 

The NIC Sponsored events

Sprinkled in amongst the meeting program were three NIC sponsored events, the first of which was the New Investigators Technology Session that focused on the advancements and utilities of single-cell RNA-seq technology in hematological research. This session featured two talks, the first by Bertie Göttgens (University of Cambridge, UK) who discussed platforms and bioinformatic methods for analyzing of single-cell RNA-seq data and the second by Doug Hinerfeld (Fluidigm, San Francisco, US) who discussed the applications for existing Fluidigm systems but also tantalized us with Fluidigm technologies in the pipeline. The second session, the New Investigators Meet-the Expert session, took place on a lovely San Diego evening following the first poster session and provided trainees the opportunity to carry on scientific (and non-scientific) conversations with mavens of the experimental hematology world.

 

The third and final session was the New Investigators Career Session, which was a jam-packed one-hour that featured talks from Keith Humphries (Experimental Hematology, CA) and Sheila Charia (Cell Stem Cell, US), who both provided advice and insights for submitting manuscripts. The career session also included talks from Gerald de Haan (University Medical Center Groningen, NLD) and James Palis (University of Rochester Medical Center, US), who discussed grantsmanship techniques as well as Terry Bishop (NIDDK/NIH, USA) who provided advice from those within funding agencies.

 

Special Sunday

The last day of the ISEH meeting was by no means the least. Following a morning of great oral presentations, Sunday concluded with three very special sections.

 

1.   New Investigator Awards Session: “And the Winner is…”

One of the most important sessions of the annual meeting is the “New Investigator Award Session”, which this year was opened by our invited New Investigator Speaker; Dr. Vijay Sankaran (Boston Children’s Hospital, Dana-Farber Cancer Institute Boston and the Broad Institute, US). Dr Sankaran started his own laboratory only three years ago, and has already made incredible contributions to the field of hematology through his studies of rare mutations resulting in blood disorders and population based studies of variation in blood cell traits. Dr. Sankaran’s talk included a story on how genetic studies on a young patient with Diamond Black Fan anemia, which in spite of a successful bone marrow transplantation remained transfusion dependent, lead to the identification of a mutated form of the erythroid promoting hormone Erythropoietin (EPO). Elegant mechanistic studies showed that the mutated form of EPO had altered binding kinetics to its receptor, resulting in defective production on red blood cells.

 

Thereafter, the top scoring abstracts from three PhD students (Sisi Chen – Indiana University School of Medicine, US, Sandra Capellera-Garcia – Lund Stem Cell Center, SE and Marissa Rashkovan – IRCM, CA) and three postdocs (Evgenia Verovskaya – UCSF, US, Benjamin Cao – Commonwealth Scientific and Industrial Organisation, AU and Nina Cabezas-Wallscheid – German Cancer Research Center, DE) were presented in a competition for the best PhD and Postdoc presentation, respectively. In fact, all participants selected for this award session were already winners and all received awards named after exceptional scientists in the field of experimental hematology, including personal prize money. However, only one could be tops, and the winner of the Dirk van Bekkum award was PhD student Sisi Chen, who shared her story on how a gain-of-function mutation in p53 disrupts epigenetic pathways, resulting in the development of pre-leukemic HSCs. First prize in the postdoc category, the Eugene Cronkite Award, went to Dr. Evgenia Verovskaya for her studies demonstrating that remodeling of the multipotent progenitor pool directly contributes to blood aging. Congratulations to you both!

 

2.   Presidential Symposium

As with each annual ISEH meeting the Presidential Symposium was a Hematologist star-studded event, with this year’s event centralizing on hematopoietic development. Nancy Speck (University of Pennsylvania, US) shed new light on the embryonic development of murine HSCs using genome-wide expression and epigenetic analyses. Len Zon’s (Boston Children’s Hospital, US) talk provided new insights about clonal diversity associated with transplantation in Zebrafish. Gordon Keller (University Health Network, US) rounded out the Symposium by improving our understanding of human hematopoietic development with data from pluripotent stem cells.

 

3.   The McCulloch & Till Award: Benjamin Ebert (Brigham and Women’s Hospital, US)

The final talk of the 2016 ISEH annual meeting was given by Ben Ebert – this year’s recipient of the McCulloch & Till award, which is presented annually to outstanding mid-career scientists in the fields of hematology and stem cells.  Dr. Ebert presented exciting findings from his lab regarding clonal hematopoiesis of indeterminate potential (CHIP) and myelodysplastic syndromes. CHIP is characterized by the presence of clonal acquisition of somatic mutations in hematopoietic cells during human aging, in the absence of cytopenia and dysplasia. This pre-malignant state is associated with an increased risk of developing myeloid or lymphoid neoplasia. Dr. Ebert’s team investigated the mutational profile of samples collected from CHIP patients and examined the phenotypic consequences of these mutations. Using exome sequencing, they identified in CHIP samples a set of common genetic lesions affecting epigenetic regulators, such as DNMT3A, TET2 and ASXL1, which are acquired during the pre-malignant state of other hematological malignancies. The identification of this set of genetic lesions will significantly improve our understanding of CHIP and the molecular mechanisms involved in the progression from this pre-malignant state to neoplasia.

 

Of note, Dr. Ebert will also be participating in the upcoming ISEH Technology Webinar: Utility of CRISPR/Cas9 Systems in Hematology Research on October 25th, 2016, 13:30 EST. Register at: https://iseh.site-ym.com/events/EventDetails.aspx?id=860256

 

Final remarks

Overall the 45th ISEH annual meeting was a success and for our concluding remarks we would simply like to thank the ISEH board of directors, the organizing committees, reviewers, ISEH staff and all of those who attended for making it such a great meeting. We apologize to those whose work we did not have space to acknowledge but we encourage all to check out the entire ISEH program, which can be found at: https://iseh.site-ym.com/page/2016program as well as the late-breaking abstract information, which can be found at: http://www.iseh.org/?page=2016Addendum.

 

 

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