Female Scientists 2021
Alexandra Stubelius, Assistant Professor at the Department of at Chemical Biology/Biology and Biological Engineering at Chalmers and Carolina Guibentif, researcher working in the Department of Microbiology and Immunology, are the two recipients of this year’s grants from the Hasselblad Foundation that support female researchers and expanding their qualifications in the natural sciences. The grant provides SEK 1 million and the opportunity to become established as an independent researcher.
Half of all childhood cancers have a suspected prenatal origin, which limits the possibility to study the cells undergoing the initial mutations, as this happens in utero. In my project, I propose to use human pluripotent stem cell cultures to study these early events, leading to childhood cancer, that take place before birth. Pluripotent stem cells can be cultured in the laboratory indefinitely and can give rise to all cell types in the body.
In this project, I focus on the development of the blood lineage, since some of the mutations found in childhood leukemia (a blood cancer) have been shown to occur before birth. In the developing embryo, with increasing organism size and complexity, the requirements for a circulation system providing oxygen, nutrients, and immunity, also evolve. Hence, the blood system develops in successive “waves”. Multiple early cell maturation waves give rise to different short-lived blood cell populations.
It is still unclear how different blood cell populations are generated in each of these early maturation waves. During my previous research, I was able to define these processes molecularly in a mouse model by using a novel technique, called single-cell RNA sequencing (scRNAseq), where we could measure the expression of every gene in each individual cell of a mouse embryo.
My plan is now to apply the same technique to in vitro differentiation of human pluripotent stem cells to blood. I will then be able to identify each intermediate step leading to the production of blood cells from human pluripotent stem cells, and chart the waves of human blood maturation that take place in the dish.
The next step will be to see how these waves of blood maturation are affected when the pluripotent stem cells contain perturbations known to predispose to childhood leukemia. For this, I will examine trisomy 21, the chromosomal abnormality that causes Down syndrome. Down syndrome children have high likelihood to develop acute myeloid leukemia, in a process that is known to start during embryonic development. However, the precise molecular mechanism is still under investigation.
My plan is to apply my approach of scRNAseq to in vitro differentiation, in the laboratory, of pluripotent stem cells towards the blood lineage, this time using pluripotent stem cells with trisomy 21. I will then be able to study how this chromosomal abnormality affects the development of the embryonic blood system, and how it may increase the chances of leukemia onset.
With this project, I will therefore establish a new in vitro platform to study how processes leading to childhood cancer already take place during embryonic development. A better understanding of these molecular processes will help develop novel cancer therapies.
Millions of people around the world are suffering from diseases such as arthritis, atherosclerosis, and fatty liver, which all get worse from inflammation, and Alexandra’s research is about developing better therapies for them.
An overactive immune system can attack the body’s own tissues, causing both allergies and chronic diseases. The most common anti-inflammatory drugs used today inhibit all immune functions – even the good defence mechanism and need to be used at high doses. These high doses result in side effects on other organs.
Alexandra Stubelius’ team develops immunomodulating nano-therapeutics, where the drugs can be directed to the right area, at the right concentration, and at the right time.
Alexandra Stubelius team uses three different strategies to develop smarter nanomedicines. First, they develop new materials, nanovesicles, that can carry existing anti-inflammatory drugs. The materials are designed to target the inflammation and deliver the drugs without damaging the surrounding tissue.
The second strategy is to create nanomaterials that can modulate the immune system. The nanomaterial acts as active substance that affects the immune response. With this method, they can fight inflammation in a new way. The aim is to interfere with the communication signals of immune cells already in the blood stream. This inhibits more immune cells to be recruited to the affected tissue and prevents the inflammation from getting worse
The third strategy is based on the discovery that the immune system not only defends out bodies, but also heals damaged tissue. The researchers examine which components that affects the immune cells in the healing process. The identified components can then be used to continue develop smarter materials for more specific immune-regulating therapies.