Postdoctoral Researcher in Normal and Malignant Hematopoiesis

Do you want to contribute to top quality medical research?

Hematopoietic Stem Cell Biology Laboratory, Dept. of Medicine, Huddinge and Dept. of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden

We are looking for highly motivated and talented postdoctoral candidates to take the lead on challenging research projects in the lab of Professor Sten Eirik W. Jacobsen. The positions and corresponding research projects are focused on regulation of normal and malignant hematopoiesis and hematopoietic stem cell biology, and will be funded by existing grants, including from the Swedish Research Council and the Knut and Alice Wallenberg Foundation. The position will be for two years with a possible extension for up to two additional years.

Research Focus and Projects

The research in the Jacobsen lab is focused on understanding the commitment pathways governing lineage fate decisions from hematopoietic stem cells (HSCs) to mature blood cells (references 1-5) and how these are dysregulated in hematologic malignancies (references 6-9). This is studied primarily in mouse models, but also in relevant patients. Key technologies applied towards these research questions include high-throughput DNA and RNA sequencing including single cell analysis, genetic fate-mapping, flow cytometry, mouse genetics, and various in vitro and in vivo stem cell assays.

One postdoc candidate will be considered for each of the following projects:

1. Unraveling HSC heterogeneity and its role in normal, clonal and malignant hematopoiesis (references 1-3).
2. The role of alternative lineage commitment pathways for platelet replenishment (references 1-3).
3. Immune surveillance and T cell receptor (TCR) targeting of stem cells in normal and malignant hematopoiesis (references 8-11).

Projects will be pursued in part at the Center for Hematology and Regenerative Medicine (HERM), and in part at the Department of Cell and Molecular Biology (CMB). The Jacobsen lab has ongoing strong collaborations related to each of the listed projects, at the Karolinska Institutet as well as internationally, and the recruited postdoctoral candidates will benefit from interactions in a highly collaborative network.

Responsibilities

Members of the research group and collaborators interact closely and regularly on each of these research projects which are conducted primarily in mouse models but also with relevant patient material. Key technologies applied towards these research questions include advanced flow cytometry, mouse genetics, TCR targeting of stem cells, high-throughput DNA and RNA sequencing including single cell analysis, and various in vitro and in vivo assays. The postholder must enjoy teamwork and interact well with others, including other members of lab, as well as collaborating scientists. Good written and oral communication skills are required for regular presentations of data and project plans.

Essential requirements

• PhD degree. Preference will be given to those who were awarded a PhD or attained equivalent research competence no more than five years prior to the expiry of the application period for the position as Postdoctoral researcher.
• Strong track record as evidenced by one or more first author high impact publications or manuscript(s) in relevant research fields.
• Training in international leading laboratories.
• Good knowledge of spoken and written English.
• Excellent interpersonal and communication skills.
• Demonstrate ability to organize, plan and document experimental bench-work.
• Ability to stay on top of the relevant research field.

Desired requirements

• Experience with advanced state-of-the art flow cytometry (projects 1-3).
• Experience with single cell RNA and DNA seq analysis (projects 1-3).
• Experience with mouse models (projects 1-3).
• Experience with mouse models of normal and malignant hematopoiesis (projects 1-3).
• Expertise in platelet biology (project 2).
• Expertise in T-cell immunology and specifically with TCRs, preferably in mouse models (project 3).

References  

1. Carrelha J., et al., Alternative platelet replenishment pathways initiated by distinct stem cells. Nat Immunol, 2024. 25(6): p. 1007-1019.
2. Carrelha J., et al., Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells. Nature, 2018. 554(7690): p. 106-111.
3. Sanjuan-Pla A., et al., Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy. Nature, 2013. 502(7470): p. 232-236.
4. Drissen R, et al., Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing. Nat Immunol 2016. 17(6): p. 666-676. (Cover article)
5. Luis T.C., et al., Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors. Nat Immunol, 2016. 17(12): p. 1424-1435.
6. Woll P.S., et al., Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer Cell, 2014. 25(6): p. 794-808.
7. Booth C.A.G., et al., Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors. Cancer Cell, 2018. 33(2): p. 274-291 e8.
8. Dimitriou M., et al., Identification and surveillance of rare relapse-initiating stem cells during complete remission post-transplantation. Blood 2024. 143(11): p. 953-966. (Plenary paper)
9. Giustacchini A., et al., Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. Nat Med, 2017. 23(6): p. 692-702.
10. Ali M., et al., T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes. Nat Biotechnol 2022. 40(4): p. 488-498.
11. Giannakopoulou E., et al., A T-cell receptor targeting a recurrent driver mutation in FLT3 mediates elimination of primary human acute myeloid leukemia in vivo. Nat Cancer, 2023. 4(10): p. 1474-1490.

What do we offer?

A creative and inspiring environment with wide-ranging expertise and interests. Karolinska Institutet is one of the world's leading medical universities. At Karolinska Institutet, we conduct successful medical research and hold the largest range of medical education in Sweden. At KI, you get to meet researchers working with a wide range of specialisms and methods, giving you ample opportunity to exchange knowledge and experience with the various scientific fields within medicine and health. It is the crossover collaborations, which have pushed KI to where it is today, at the forefront of global research. Several of the people you meet in healthcare are educated at KI. A close relationship with the health care providers is important for creating groundbreaking top quality education and research. Karolinska Institutet is also a state university, which entitles you to several benefits through our collective agreement.

Location: Flemingsberg

Center for Hematology and Regenerative Medicine (HERM)

 Professor Sten Eirik W. Jacobsen.

Department of Cell and Molecular Biology (CMB)

Application

Applications must contain the following documents in English or Swedish:

1. A maximum one page cover letter summarizing motivation for the position, one or more of the research projects listed, and previous experience and research interest.
2. A complete curriculum vitae of current work and work history.
3. A complete list of publications with any shared authorships clearly indicated.
4. Names and contact details of three references who are familiar with the applicant’s recent research and training.

The application is to be submitted on the Varbi recruitment system.

Karolinska Institutet is one of the world ́s leading medical universities. Its mission is to contribute to the improvement of human health through research and education. Karolinska Institutet accounts for over 40 per cent of the medical academic research conducted in Sweden and offers the country ́s broadest range of education in medicine and health sciences. Since 1901 the Nobel Assembly at Karolinska Institutet has selected the Nobel laureates in Physiology or Medicine.

Pursuant to the regulations of the Swedish National Archives, applications are kept on file for two years after the appointment has gained legal force. The regulations do not apply to attachments that have been printed or otherwise published.

Karolinska Institutet strives to provide a workplace that has approximately the same number of women and men, is free of discrimination and offers equal opportunity to everyone.

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Application deadline:  2025-03-16.

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