Postdoctoral research fellow - Improving adoptive NK cell immunotherapy against leukemia by optimization of the conditioning regimen along with modulation of the NK cell graft

Updated: about 2 months ago

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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). As part of the project, the Postdoctoral Fellow will also address the potential of genetically engineer NK cells for augmented homing to bone marrow and lymph nodes.

Research group

Assistant Professor Dr. Mattias Carlsten M.D. Ph.D. 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. 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 2017, 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. NK cells will also be manipulated to have improved homing potential to the bone marrow and as a part of a larger project control homing to other organs such as lymph nodes and liver.

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. Applicants who have not completed a doctorate at the end of the application period may also apply, provided that all requirements for a completed degree are met before the (intended) start date of the post doctoral education.

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

Your profile

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 AML growth in mice, harvest organs including bone marrow and lymph nodes, adoptive cell transfer, drug delivery, sampling and imaging, but also vast experience in running immunology assays and cytokine/chemokine assays are welcome to apply. Having hands-on experience in preparing and developing components for genetic manipulation of lymphocytes, preferably NK cells is a merit. Experiences of running ex vivo models of homing and lymphocyte/endothelium interactions is a plus. Knowledge in tumor immunology and gene modification of cells is strongly preferable. State-of-the-art experience with multiparameter flow cytometry and analysis is requirement.

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. A track-record of supervising younger students is a plus. 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.

Location: Flemingsberg

Type of scholarship

This is a full-time fixed-term appointment for 12 months, with possibilities for extension depending on scientific progress. 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.

Research environment at the research center HERM within Department of Medicine, Huddinge

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.

Application process

An 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)

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

Welcome to apply at the latest 2021-04-16.

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