7 September

Thesis defense Sasja Blokzijl-Franke: “Hematopoiesis in the developing zebrafish embryo”

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Sasja Blokzijl-Franke, from the group of Jeroen den Hertog, successfully defended her thesis “Hematopoiesis in the developing zebrafish embryo” on 7 September 2021. She studied the formation of blood and the influence of various factors, including PI3K signaling, on this process. Additionally, she researched a mutation in the SHP2 protein that is involved in the development of a rare form of leukemia in children with the Noonan Syndrome (NS), a rare developmental disorder. With her thesis, Blokzijl-Franke demonstrates the suitability of the zebrafish model for research into (human) embryonic development.

Blood supplies the body with oxygen and nutrients, removes waste, transports hormones and plays an important role in the functioning of the immune system. Blood consists of various components, including red- and white blood cells and platelets. Because these blood cells all have a limited lifespan, new cells are constantly produced.

Specialized cell

The process during which all cellular components of blood are produced is called hematopoiesis. The production of blood cells is primarily conducted by hematopoietic stem cells (HSC). When such HSCs divide, they are able to form both a new HSC and a (progenitor of a) more specialized cell, such as a red- or white blood cell.

Zebrafish as a model

Zebrafish can be used as a model for research into hematopoiesis. That is because the embryonic development of zebrafish is comparable to that of humans. But there are also differences, for example during hematopoiesis. In zebrafish, a specialized HSC is not distinguishable from its progenitors. Researchers therefore use a mix of these cells for their experiments and call them ‘hematopoietic stem/progenitor cells (HSPCs).

PI3K signaling

During her research, Sasja Blokzijl-Franke studied the hematopoiesis and the influence of various factors on this process in zebrafish. She for instance studied PI3K signaling, which is responsible for the regulation of cellular responses such as cell division on external factors. Cell division needs to be tightly regulated, because uncontrolled cell division can lead to cancer. Normally, the gene Pten ensures that PI3K signaling, and therefore cell division, is inhibited.

Abnormal hematopoiesis

Blokzijl-Franke and her colleagues found that a part of the HSPCs disintegrated in zebrafish with a non-functioning Pten gene. Additionally, inhibition of PI3K signaling in normal embryos led to abnormal hematopoiesis. When the researchers compensated for the lack of Pten or inhibited PI3K signaling, the hematopoiesis normalized. From these results, they concluded that the level of PI3K signaling is important for the emergence of HSPCs: too much as well as too little activity leads to the death of these cells.

Noonan syndrome

Besides further research into the influence of PI3K signaling on hematopoiesis, Blokzijl-Franke studied a specific mutation in the SHP2 protein that occurs in people with the Noonan Syndrome (NS). NS is a developmental disorder characterized by for example a short body length, heart defects and specific facial features. Furthermore, a rare form of leukemia occurs in a part of the children with this syndrome. Together with her colleagues, Blokzijl-Franke discovered that an inflammatory response may be involved in the development of this form of leukemia. Zebrafish with the SHP2 mutation that were administered anti-inflammatory medicine developed less serious blood defects.

Modeling human disease

In her thesis, Blokzijl-Franke also describes her additional research into the SHP2 protein and its involvement in PI3K signaling and hematopoises in zebrafish. Altogether, she demonstrates the suitability of zebrafish as a model for research into embryonic development and modeling human disease.

Picture Sasja Blokzijl-Franke

 

 

 

Now that she obtained her PhD, Sasja Blokzijl-Franke is orienting herself on the next step in her career.