Karolinska Institutet, The Department of Medicine, Huddinge

Postdoctoral studies (scholarship): Improving adoptive NK cell immunotherapy against leukemia by optimization of the conditioning regimen along with modulation of the NK cell graft

We are seeking a highly motivated and ambitious individual to join the research group of Mattias Carlsten as a Postdoctoral Fellow. The project will focus on elucidating the role and timing for cytoreductive therapy prior to adoptive natural killer (NK) cell infusion to facilitate their ability to infiltrate bone marrow compartments and thereby improve the targeting of acute myeloid leukemia (AML).

Research group
Assistant Professor Dr. Mattias Carlsten M.D. Ph.D. (http://ki.se/en/people/mattca) was recruited from the National Institutes of Health (NIH) 2015 and is currently expanding his translational research group at the Karolinska Institute. The group is located at HERM, Department of Medicine, Huddinge (MedH), Karolinska Institutet (http://ki.se/medh/herm). The main research focus of Dr. Carlsten’s group is to study how the immune system can be utilized to treat cancer (Björklund, Carlsten, Sohlberg et al. Clin. Can. Research 2018, Carlsten et al. Clin. Can. Research 2016, Carlsten et al. Frontiers in Imm. 2016, Childs et al. Nature Reviews Drug Discovery 2015). More specifically, the group focuses its work around basic biology as well as genetic engineering of NK cells and donor lymphocyte infusion grafts with the overall aim of applying new discoveries in settings of cellular cancer immunotherapy. The group is also addressing how drugs can be utilized to facilitate and syngergize with immune cells to more efficiently and specifically target the cancer (Carlsten et al. OncoImmunology 2018). As a physician-scientist, Dr. Carlsten’s work is stretched from pre-clinical in vitro studies, including bench work and animal models, to early clinical trials involving cellular cancer immunotherapy and immunomodulating drugs. The group will now address the role and timing for cytoreductive therapy to augment the efficacy of adoptively infused NK cells by making space for the cells and potentially restore key pathways that guide the cells to the bone marrow where they can target the leukemia.

Project description
The project will focus on the role and timing of cytoreductive therapy to improve the infiltration and persistence of adoptively infused NK cells in the bone marrow. Although data from other bone marrow malignancies have indicated that this is pivotal for successful tumor targeting, it has not yet been explored systematically for NK cell-based immunotherapies against AML. As part of the project, work will also be focused on how NK cells can be modified to further improve their ability to persist in vivo, including in the leukemia-containing bone marrow environment. These in vitro and pre-clinical animal studies will be paralleled with studies of samples from AML patients treated with standard induction and consolidation chemotherapies at the Karolinska University Hospital. The position provides an exciting opportunity for the successful candidate to apply cutting-edge technology and excel in the space between bench work, animal work and clinical studies towards establishing the role for conditioning to improve the therapeutic efficacy of NK cell-based immunotherapy against AML. The work will involve mouse experiments along with cellular and molecular biology techniques and assays.

The position
We are seeking a highly talented and enthusiastic researcher who holds a Ph.D. degree and has a solid background in immunology and work with xenograft animal models as well as a strong track record. Candidates with extensive experience in performing animal work, including establishing primary AML growth in mice, adoptive cell transfer, drug delivery, sampling and imaging, but also vast experience in running immunology assays and cytokine/chemokine assays are welcome to apply. Knowledge in tumor immunology and gene modification of cells is strongly preferable. State-of-the-art experience with multiparameter flow cytometry and analysis is an important merit.

The successful candidate should have excellent interpersonal and communication skills, organizational skills, and the ability to work productively and dynamically in a team. The latter is key. Self-motivation and the ability to stay on top of the relevant research field is an absolute requirement. Applicants must be able to integrate well into the international and multidisciplinary research environment. Excellent knowledge of spoken and written English is a requirement.

Entry requirements
Scholarships for postdoctoral qualification can be established for foreign researchers who place their qualifications in Sweden. The purpose of scholarships for postdoctoral qualification is to promote internationalization and contribute to research qualification after a doctorate or equivalent.

A scholarship for carrying out postdoctoral research can be granted for a maximum of two years within a four year period following the receipt of a doctoral degree or equivalent.

To be eligible for a postdoctoral scholarship, the person must have obtained a doctorate or a foreign degree deemed to be equivalent to a doctorate. Postgraduates who have yet to graduate may apply if their thesis defense is scheduled to take place within three months after the application deadline, in which case verification from the Dissertation Committee, or equivalent body, must be submitted with the application.

The head of the department determines whether their previous training and scholarly qualifications correspond to a Swedish doctorate or higher.

Type of scholarship
The amount is tax free and it is set for twelve months at a time, paid out on a six months basis. In exceptional cases, shorter periods may be acceptable.

This is a full-time fixed-term appointment for 24 months, with possibilities for extension depending on scientific progress.

Application process
An employment application must contain the following documents in English or Swedish:

  • A complete curriculum vitae, including date of the thesis defence, title of the thesis, previous academic positions, academic title, current position, academic distinctions, and committee work
  • A complete list of publications
  • A summary of current work (no more than one page)
  • Verification from the thesis defense committee or the equivalent (only if the thesis defense is scheduled within four months after the application deadline).
  • 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.

Research environment
The Center for Hematology and Regenerative Medicine (HERM) at the Department of Medicine, Huddinge, consists of approximately 90 research fellows and is a nationally leading and internationally competitive environment for studies of the human immune system in the context of malignancy and infectious diseases. At HERM, the groups are part of a highly interactive research environment within basic immune cell biology, cellular immunotherapy along with cellular and molecular regulation of hematopoiesis in health and disease. HERM is also tightly connected with clinical researchers and healthcare teams at several departments of the Karolinska University Hospital, including Center for Hematology, which allows for research involving clinical material and the potential to bring new therapies from bench to bedside. The laboratories at HERM offers state-of-the art cell culture, molecular biology, flow cytometry and microscopy facilities. The vision is to become one of the leading translational research centers within hematopoiesis and immunity in Europe.

Type of employment Postdoctoral studies.
Contract type Full time
First day of employment According to agreement
Number of positions 1
Full-time equivalent 100%
City Huddinge
County Stockholms län
Country Sweden
Reference number 2-253/2019
Contact
  • Assistant professor Mattias Carlsten, mattias.carlsten@ki.se
Published 14.Jan.2019
Last application date 03.Feb.2019 11:59 PM CET

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