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ISEH Connections April 2015
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April 2015

About ISEH

The mission of ISEH is to promote the scientific knowledge and clinical application of basic hematology, immunology, stem cell research, cell and gene therapy, and all related aspects through research, publications, discussion, support of new investigators and organization of scientific meetings.

Table of Contents

President's Message
New Investigator Digest
News from the Field
Don't Miss Sessions
Member Profile
Society News
Experimental Hematology
Member Corner

Donate now to the ISEH New (Junior) Investigator Travel Grant fund


 

Save the Date for the 44th Annual Scientific Meeting
17-19 September 2015
Kyoto, Japan


Interested in submitting an article to Experimental Hematology? 

Learn more about fast track submissions here.

Articles are reviewed within 7-10 days of submission. 

President's Message: The ISEH Fountain of Youth

At the core of the ISEH's mission is help young Experimental Hematologists to become tomorrow's leaders of the field. Toward this end, ISEH provides travel grants and awards to new investigators that submit cutting edge abstracts for discussion at the Annual Meeting. The New Investigator Session of the meeting recognizes the six highest ranked abstracts submitted for presentation, with three students and three postdoctoral trainees honored with named awards and highlighted oral presentations.

New Investigators are a main driving force of ISEH and we are very lucky to have an exceptionally active and vibrant New Investigator Committee (NIC) that works to provide our members with ongoing events and services throughout the year. The NIC maintains three social media outlets that allow the ISEH community to interact outside the Annual Meeting. Social media such as Facebook, LinkedIn and Twitter. ISEH sites have over 600, 230 and 150 members, respectively. As well as being used to share ad hoc posts that are of interest to general ISEH membership and provide interviews with prominent ISEH members, the sites are used to host a regular online journal club where the participants can ask questions directly to the first authors of high impact publications. Subscribers to the Facebook group can vote to decide which paper is going to be the next one to be discussed at the journal club. In addition, the NIC writes a regular column for the ISEH newsletter covering topics such as tools for online education, improving your public speaking skills, early career grant writing and a review of the ISEH Annual Meeting.

The NIC also contributes to the continued education of our members through a very successful webinar series, which has featured webinars on the stem cell niche (David Scadden and myself), normal and leukemic stem cell heterogeneity (John Dick and Gerald de Haan) and hematopoietic specification from pluripotent cell lines versus reprogramming of somatic cells (George Daley and Derrick Rossi). Based on this success, the NIC aims to provide three webinars per year, one of which will have a focus on emerging technologies. Make sure not to miss the next webinar on the clonal evolution of pre-leukemic HSCs in AML  by Ross Levine and Ravi Majetiwhich will take place on the 3rd of June, 14:30 to 16:00 EST. All the webinars are recorded and available free of charge to our members.

For this year's Annual Meeting, the NIC has modified the format of the Meet the Expert session to a “Meet the Expert Mixer”. The session will follow a "speed dating" format where new investigators will meet with up to four prominent PIs over drinks and snacks. Participants will be invited to chat with any of six experts: Elaine Dzierzak, Andreas Trumpp, Paul Frenette, Fernando Camargo, Irv Weissman and Hiro Nakauchi. At 20 min intervals the participants will then be invited to switch tables to maximize the networking opportunities. The NIC will host the lecture by Dr. Fernando Camargo and present a workshop on careers that will focus on preparing for a scientific job interview. Attendees will have the opportunity to listen to the experience of senior faculty responsible for recruiting junior faculty, post-docs and PhD students (Peggy Goodell, Takashi Nagasawa and Hartmut Geiger) and a recently appointed Assistant Professor (Daniel Lucas) as they describe the process of preparing for a scientific job interview. The workshop will incorporate a breakout session to allow the opportunity to ask the expert panel follow up questions in smaller groups.

None of these wonderful activities and events would be possible without the New Investigators who believe in ISEH's mission and work tirelessly to carry it forward. On behalf of all our members, I would like to express our sincere gratitude to the NIC for giving so generously of their time to support and promote our Society

Sincerely,

Paul Frenette
ISEH President  

New Investigator Digest

Research: The Science of Overcoming Failure

Eugenia (Kena) Flores-Figueroa1, Stephen Sykes2

1.Oncological Research Unit at the Mexican Institute of Social Health, Mexico City, Mexico. 2. Fox Chase Cancer Center Blood Cell Development and Function, Philadelphia, USA.

"Perceived failure can become the catalyst of profound re-invention"
Conan O'Brien

On a cold Spring Sunday morning in Western New Hampshire, Conan O’Brien, a Harvard alumnus, stood in front of 1,700 Dartmouth students for a commencement address. After initially teasing them about having an inferiority complex (as part of the Ivy League Colleges), he then said something that was as unexpected as it was wise, “Whether your fear it or not, true disappointment will come, but with disappointment comes clarity, conviction and true originality.” For those who are not familiar with O’Brien’s work, he is not a scientist, although his speech seemed to be tailor-made for research. He is a very famous comedian that experienced failure shortly after reaching his lifetime goal (O’Brien became the host of the Tonight Show but was fired soon thereafter).

Scientists face disappointment and/or failure on a daily basis; a failed experiment, a rejected paper or grant. However, failure does not naturally lead to clarity, conviction and true originality; you have to make it happen. For young students, failure can sometimes lead to the premature departure from graduate programs, changing careers or even depression. Those who have walked the scientific path long enough have learned that failure is just part of success and that overcoming failure is an essential part of your training. So as a young scientist, try to embrace your failures and, as Dr. Peter van Galen, suggests, revel in the brief successes to get you through the low points, “It is pretty rare for an experiment to confirm your hypothesis, so you have to savor the times that it happens. The percentage of experiments that yield 'publication quality' data is probably less than 10%, and it’s these rare events that have to keep you going for months of disappointments."

Dr. Hector Mayani, remembers that as a student and a young investigator, failure was depressing, but after 20+ years as an independent scientist he learned how to manage it. As he stated, “failure still knocks at my door every now and then. I still do not like it, but the difference is that I have learned how to handle it.” We should not fear failure, but change our paradigm about it; for Dr. Sean Morrison, failure is an opportunity, he recognized that “You learn more from the failures than from the successes. Failures aren't fun but the experiences can make you a better scientist.”  Read more on website.

News From the Field


FDA Grants Breakthrough Therapy Designation to LentiGlobin for Treatment of Beta-Thalassemia Major

ACGT Surpasses $25 Million Funding Milestone with Two New Grants

Europe Approves Holoclar®, the First Stem Cell-Based Medicinal Product

T-Cell Therapy Clinical Trial Now Offered to Cancer Patients at C.S. Mott Children’s Hospital

Medigene Starts Phase I/II Study with DC Vaccine to Treat Acute Myeloid Leukemia (AML)

Immunovaccine Initiates Phase II Clinical Trial of DPX-Survivac Immunotherapy in Recurrent Lymphoma

AOP Orphan Pharmaceuticals Announces Progress of Pivotal Phase III Trial PROUD-PV Applying Ropeginterferon Alfa 2b, a Novel, Long-Acting, Mono-Pegylated Interferon for Treatment of Polycythemia Vera

Sangamo BioSciences Announces FDA Acceptance of IND to Initiate Clinical Trial of its Novel ZFP Therapeutic® for Beta-Thalassemia

IMBRUVICA® (Ibrutinib) Treatment Shows Efficacy and Tolerability in Heavily Treated Chronic Lymphocytic Leukemia Patients following Allogeneic Stem Cell Transplant

MEI Pharma Announces Top-Line Data from Randomized Phase II Clinical Study of Pracinostat in Front-Line Myelodysplastic Syndrome

Cellerant Announces Dosing of First Patient in Randomized Phase II Clinical Trial of CLT-008 in Acute Myeloid Leukemia Patients

UW to Test ‘Breakthrough’ Pediatric Leukemia Treatment

Don't Miss Sessions

American Society of Gene & Cell Therapy 18th Annual Meeting
New Orleans, LA, USA - 13-16 May 2015
This is the largest gene and cell therapy conference in the world, with 19 scientific symposia and attended by 1,700 of the world’s top researchers, clinicians, fellows, and trainees. This year's plenary lectures will be given by Drs. Steven Rosenberg and Anthony Atala.

Stem Cells in Drug Discovery - Cambridge Workshop Series
Cambridge, UK, 2-3 June 2015
Attendees to this meeting will benefit from the expert knowledge of leaders in stem cell research who are currently screening for efficacy and toxicity of experimental compounds using iPS cell lines. There will also be discussions involving industry and regulatory developments that are shaping the future of drug discovery.

International Society for Stem Cell Research 
2015 Annual Meeting
Stockholm, Sweden, 24 - 27 June 2015
The meeting provides an opportunity for scientists, clinicians, educators and industry professionals to share new data, learn from peers, and discover global advances within the stem cell field. 

Find more meetings on the website.

Member Profile

Meet ISEH Member Dr. David Stachura

Dr. David Stachura, Ph.D., is an Assistant Professor in the Department of Biological Sciences, California State University, Chico. He has been working in the hematology and stem cells scientific field for 11 years and joined ISEH in 2008. His area of expertise is zebrafish and murine developmental hematopoiesis and developing in vitro assays to study hematopoietic progenitors. Dr. Stachura kindly accepted Connection's invitation to participate in a Q&A session. Below he shares with us his path to a tenure position, his love for teaching, the reasons behind his lab's facebook page and his concern about the low level of funding for medical research in the US.

Please tell us about your graduate and post-graduate education.

I received my Ph.D. in Cellular and Molecular Biology at the University of Pennsylvania School of Medicine, working in the laboratory of Dr. Mitchell Weiss. My research was focused on devising assays to study the differentiation of murine megakaryocyte-erythroid progenitors (MEPs). After graduating, I joined the laboratory of Dr. David Traver at the University of California San Diego to study zebrafish hematopoiesis and develop assays to more carefully interrogate zebrafish hematopoietic stem and progenitor cells (HSPCs).

How did you find your way to the hematology and stem cells scientific field?

I first became interested in hematopoiesis when I saw a talk that my graduate mentor gave at Penn. I had worked on microtubule dynamics before that, and was utterly fascinated by the idea that one cell (the hematopoietic stem cell; HSC) could generate the multitude of blood cells needed by an organism for its whole life. I instantly was interested in discovering how these cells functioned.

Who has most influenced you to become a scientist, and how did they influence you?

Ever since I was a child I wanted to be a scientist. My parents were teachers, and we were always camping, exploring, and learning about biological phenomena when I was a kid. The person that helped me realize that I could be a scientist (as a career) was Dr. Lynne Cassimeris at Lehigh University. I worked in her laboratory as an undergraduate researcher studying cell fusion; after that I was hooked, and applied to graduate school.


Read more on website.

Society News

A Webinar Review: Defining the Map Back to Stemness

By: Eirini Trompouski and Teresa V. Bowman

Thousands of bone marrow transplantations take place each year in US alone. Although broadly employed, the use of transplantation is hampered by the lack of appropriate donor cells. Even when there is a matched donor, the number of cells is often insufficient, thus hampering the full utility of the therapy. There is clearly an immediate need to enhance our ability to create or expand hematopoietic stem cells (HSCs). To this end, George Daley and Derrick Rossi, both from Harvard Medical School, presented their approaches, for overcoming this challenge at the most recent ISEH webinar entitled “Hematopoietic specification from pluripotent cell lines vs. reprogramming of somatic cells” (now available for online viewing for ISEH members. Click here to view.)

Reprogramming of differentiated cells to progenitor cell types holds great promise for medical applications. However, reprogramming to HSCs has proven particularly challenging. The Daley and Rossi groups as well as others including the webinar moderator, Kateri Moore and her group from Mt. Sinai Hospital, have devised approaches to reprogram various cell types back to a multipotent state. Dr. Daley’s group is striving to impart long-term multilineage potential to embryonically derived human hematopoietic progenitors. His lab has established a protocol to direct human embryonic stem cells or induced pluripotent stem cells to a primitive myeloid progenitor. Using this population as starting material and following a Yamanaka-like strategy to reprogramming, Daley’s group determined that five factors (HOXA9, RORA, ERG, SOX4, and MYB) were sufficient to promote multipotent engraftment potential (Doulatov et al. Cell Stem Cell 2013). They have now expanded the transcription factor repertoire to include NFIA and DACH2, which are needed to convey better lymphoid potential, a population that is usually under-represented in most blood-forming efforts. Finally, Dr. Daley also showed that these methods can be successfully used to model human disease. He presented an unpublished model of a hereditary blood disorder, Diamond-Blackfan Anemia, demonstrating that many facets of the disease can be recapitulated both in vitro and in vivo. He ended with a short vignette on a chemical screen that uncovered autophagy as a novel therapeutic target for suppressing the erythroid defects in DBA.

Read more on website. 

Register Now for the ISEH Webinar: Clonal Evolution of Pre-Leukemic HSCs in AML

Wednesday, 3 June 2015, 2:30 - 4:00 pm EST 

The identity of the cell of origin for hematologic malignancy as well as the mechanism via which cellular transformation is achieved, have both been topics of much debate within the hematology community for many years. The advent of next generation sequencing technologies has provided a route through which increased resolution of this process can be attained. Using this technology, a number of recent high profile publications have characterized an age-associated increase in the genomic mutation frequency within the hematopoietic stem cell compartment associated with non-malignant expansion of individual stem cell clones. Frequently, these mutations occur in epigenetic modifiers such as DNMT3a, IDH1/2 and TET2, which are also often found in leukemia. This suggests that epigentic instability may be a major driving force in this clonal evolution and that this process may be an age-related step towards transformation.

In the next ISEH webinar, two leaders in this field, Drs. Ross Levine and Ravi Majeti, will discuss the recent advances in this research topic and  the insights that their work brings to our understanding of HSC clonal evolution during aging and its relationship to leukemogenesis. Dr. Ross Levine is a physician scientist at Memorial Sloan Kettering Cancer Center, New York, who leads a research group that has a major focus on understanding the genetic basis of myeloid malignancies. Dr. Ravi Majeti is also a clinician scientist who leads a research group based at Stanford School of Medicine with research interests centred on the characterization and targeting of leukemia stem cells.

The webinar will take place on Wednesday 3 June 2015 at 2:30 to 4:00 pm EST and will be moderated by Dr. Ann Mullally, Assistant Professor of Medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston. Be sure to register to see what promises to be a great webinar on one of the current hot topics in hematology led by world-renowned experts in the field. This will be followed by an interactive discussion where you can submit questions to any of the webinar participants.


 

 

ISEH Career Center: New Lower Posting Rates

The ISEH Career Center has decreased the cost for job posts. The new flat fee of $250 (USD) is for posts 2000 - 3000 characters. The post will run for 60 days on the ISEH Career Center and will be featured in ISEH Connections. Recruit the top new investigators from ISEH for open post-doc or faculty positions for your lab! Click here to submit an ad today. 

Experimental Hematology

Inside Experimental Hematology: March and April 2015

Mutant forms of c-Cbl and FLT3 cooperate to enhance myeloid leukemia development

Potential targeting of B-cell lymphoma 2–associated AthanoGene-1 (BAG-1) in poor responding pediatric AML patients

Autophagy regulates hematopoietic stem and progenitor cell cycle

Melatonin overcomes resistance to clofarabine in two leukemic cell lines by increased expression of deoxycytidine kinase

Csf1r collaborates with a C-terminal mutant of C/EBPα to develop aggressive AML

BIRB796 stimulates hematopoietic progenitor stem cell growth in FANCA

The antimalarial drug artemisinin depletes erythrocytes

Bone marrow failure in C57BL/6 mice

 

Read more on website.

Members' Corner

Congratulations to ISEH members!

Congratulations to:

Irving Weissman, who was awarded a grant from the California Institute for Regenerative Medicine through the agency's "tools and technology" grant program to develop ways to generate better-tolerated, transplantable, blood-forming stem cells from induced pluripotent stem cells and to test new ways to prepare recipients for the transplantation of the cells.

Irving Weissman also won this year’s Charles Rodolphe Brupbacher Prize for Cancer Research for his work on healthy and sick stem cells.

Hanna Mikkola, who received the prestigious California Institute for Regenerative Medicine tools and technology award for her work creating a suite of engineered human pluripotent stem cell lines to facilitate the generation of patient specific hematopoietic stem cells.


Congratulations to the following members for the recent publication of their ground-breaking research:

Timm Schroeder, Hartmut Geiger, Michael A. Rieger, Marieke A. G. Essers, David A. Williams, Andreas Trumpp and Michael D. Milsom: Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells. Nature, 2015; Feb 18. [Epub ahead of print]

Shahin Rafii: Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells. J Clin Invest., 2015;125(3):1243–1254.

David G. Kent, Anna L. Godfrey and Anthony R. Green: Effect of Mutation Order on Myeloproliferative Neoplasms. N Engl J Med., 2015; 372:601-612

John E. Dick: CDK6 Levels Regulate Quiescence Exit in Human Hematopoietic Stem Cells. Cell Stem Cell, 2015 Mar 5;16(3):302-13.

Read more on website

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