Exploring Experimental Hematology: Modeling human RNA spliceosome mutations in the mouse: not all mice were created equal

Chances are, you came across this hashtag last month: #10yearschallenge. Whether it was you or your Hollywood crush, you know it: people posted 2009/2019 side-by-side pictures on social media. Some people used it to spark up a conversation on climate change, “What Earth will look like in 2029?” Others (well, myself) thought instead: “What is the #10yearschallenge in cancer research?

Across the globe, population aging is becoming one of the biggest social transformations of this century. By 2029, almost 1 in every 5 residents in the U.S. will be of retirement age. Aging is a risk factor for virtually every cancer, and this means that our current challenge is to understand, and to model age-associated cancers, such as myelodysplastic syndrome (MDS) and related myelodysplastic/myeloproliferative neoplasms (MDS/MPN). In their review, “Modeling human RNA spliceosome mutations in the mouse: not all mice were created equal”, Carl Walkley and colleagues go over the murine models recapitulatin…

How to Handle Scientific Rejection

Rejection.  If you asked people on the street, what they think of when they hear this word most people would relate to unsuccessful romantic attempts, perhaps being denied a car or mortgage loan, or even having your layup attempt swatted into the third row at your YMCA pickup basketball game.  But for research scientists this word conjures up different connotations – usually conveying unsuccessful attempts at applying for jobs, funding or publishing manuscripts in peer-reviewed journals.  For most of us, ~80% of all such attempts are unsuccessful and thus come back with an email containing the dreaded “R” word.  Given that academic PIs spend the majority of their time writing grants and papers, one must find ways to deal with rejection if they are to overcome the obstacles and pursue a successful research career.

From my own perspective (faculty for 6.5 years), it has been something that I have to consciously make an effort not to take personally.  You pour in so much of your blood, s…

Simply Blood Lab Spotlight: Challen Lab

Each month, Simply Blood spotlights a lab focused on the research of basic hematology, immunology, stem cell research, cell and gene therapy, and other related aspects.  Get to know these different labs around the world! This month, we are featuring the Challen Lab at Washington University School of Medicine in St. Louis, Missouri, USA.

How long have you had your lab? 
I have been independent faculty at Washington University School of Medicine (St. Louis, USA) for 6.5 years.

How many members make up your lab?  Students/postdocs?
We currently have 7 permanent members of the lab (3 students, 2 post-docs, 2 technicians), plus a rotating cast of other characters (undergraduates, summer students, rotation students).

What is the major research theme of your lab?
Our laboratory research focuses on the epigenetic regulation of normal and malignant hematopoiesis.  That is, how do epigenetic factors regulate the balance between self-renewal and differentiation in hematopoietic stem cells (HSCs), …

New Investigators Committee Recap of the 2018 ISEH Annual Meeting in Los Angeles

A Recap from Heather O'Leary and the 2017/18 New Investigators Committee

ISEH is known for providing its attendees and trainees with not only great science but also many sessions to enhance networking, career evolution and technology knowledge. This article gives an overview of some of the highlighted sessions from the annual meeting, in case you missed them, as well as providing an introduction to our most recent webinar!

Technology Session:
This year, the New Investigators Technology Session focused on new advances in whole-tissue imaging and how this technology will revolutionize the way we can study the microenvironment in hematological research. Where do HSCs localize? How is the cellular HSC niche organized? Or, does HSC localization and niche composition change upon aging?  This session first featured Sandra Pinho from Paul Frenette’s laboratory (Albert Einstein College of Medicine) and Mehmet Sacma from Hartmut Geiger’s team (Universität Ulm and Cincinnati Children's Ho…

Azacitidine, venetoclax and leukemia stem cell metabolism - An interview with Courtney Jones and Daniel Pollyea by Peter van Galen

For older patients with acute myeloid leukemia (AML), a new combination therapy of azacitidine + venetoclax was recently shown to be effective and well tolerated (DiNardo et al., 2018). Recent work that came out in Cancer Cell and Nature Medicine elucidated the mechanism by which these drugs target leukemia stem cells (LSCs), that are the main drivers of AML progression and relapse. This work was in part carried out in the laboratory of Dr. Craig Jordan, who has an impressive track record of studying the biology of LSCs (Pollyea and Jordan, 2017).

In the first study, Dr. Pollyea et al. report that the combination treatment of the BCL-2 inhibitor venetoclax and azacitidine leads to superior clinical outcomes in older patients with AML (Pollyea et al., 2018). Mechanistic analyses showed that this treatment leads to inhibition of the electron transport chain complex II, disruption of the TCA cycle, and suppression of oxidative phosphorylation (OXPHOS).

In the second study, Dr. Jones et a…

Exploring Experimental Hematology: Salad or Burger for Dinner? Your Stem Cells Don't Really Care.

In this issue of Simply Blood, Evgenia Verovskaya is Exploring Experimental Hematology and highlighting and deconstructing one of her favorite manuscripts from the ISEH society journal: "Lifelong dietary intervention does not affect hematopoietic stem cell function" by Seka Lazare et al.

Across the planet, people are living longer and longer. Can we influence how healthy we age? Many studies of organismal aging indicate that healthy diet and exercise can reduce age-related morbidities. But working in the field of blood research, the question is – can dietary choices also prevent aging of hematopoietic stem cells (HSCs), and rejuvenate blood production in the elderly? The group of Gerald de Haan addressed this question using the mouse model and published their interesting findings in Experimental Hematology.

What to expect in this paper:

The de Haan group examined HSC function in C57/BL6 mice fed a high fat, low fat, or calorie-restricted diet throughout their whole life. As …

ISEH January 2019 – Message from the President: Bertie Gottgens

Dear Friends and Colleagues,

I write this message to you in the last few days of December, reflecting on the past year and pondering the year ahead.  Looking back at 2018, a real highlight for me was the 47th annual meeting of the ISEH in LA.  As I see it, our research field of experimental haematology is going through a sustained period of positive growth and momentum.  It is pleasing therefore to see that the ISEH meeting is doing such a fabulous job at capturing this sense of excitement, ranging from breakthroughs in our understanding of the fundamental principles that control blood development, all the way to achieving real clinical impact from the application of new technologies and harnessing the underlying biology.

I firmly believe that one of the main reasons behind ISEH’s ability to capture the excitement in our field is the strong emphasis on, and contribution from, our junior members.  I am delighted to see the continued enthusiasm emanating from our junior investigator c…