Improving the outcome of post-transplant leukemia relapse by genetic engineering and tracking of donor lymphocytes

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 potential of genetic engineering and manipulation of donor lymphocyte grafts to improve treatment of post-transplant leukemia relapse.

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.

Project description
The project will focus on genetic engineering and manipulation of donor lymphocyte infusion (DLI) grafts for improved bone marrow homing and leukemia targeting. The aim is to improve the tumor rejection capacity of DLIs while reducing the risk of DLI-induced graft-versus-host disease in non-bone marrow organs. The position provides an exciting opportunity for the successful candidate to apply cutting-edge technology and work towards establishing the concept of using genetically engineered DLI grafts for improved therapeutic efficacy with the overall aim of providing proof-of-concepts for clinical translation of the approach. Additionally, an important aspect of the approach is to dynamically track the infused donor lymphocytes in vivo in 3D using a unique cell tracking method established in collaboration with other researchers at Karolinska Insitutet. The work will involve cell and molecular biology assays as well as in vivo mouse experiments. 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 new innovative treatment approaches for AML.

Entry requirements
We are seeking a highly talented and enthusiastic researcher with a Ph.D. degree and a background in immunology and animal work as well as a strong track record. Candidates should have a solid background in immunology and work with xenograft animal models including GvHD as well as a strong track record. Extensive experience in performing immune assays and adoptive cell transfer into mice is a requirement. Knowledge in tumor immunology, stem cell transplantation, graft-versus-host disease (GvHD), including grading of GvHD in mice, animal imaging and gene modification of cells is strongly preferable. State-of-the-art experience with multiparameter flow cytometry and analysis is key and genetic engineering of lymphocyte, preferably T cells, via CRISPR/Cas9 and mRNA electroporation is a 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.

Postdoctoral scholarship
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.

This is a full-time fixed-term appointment for 24 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.

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.

Application process
The application must contain the following documents in English:

  • Cover letter, including a summary of the Ph.D. studies (no more than two pages).
  • A complete Curriculum Vitae, including date of the thesis defense, title of the thesis, previous academic positions, academic title, current position and academic distinctions.
  • A complete list of publications
  • 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.

Location: Flemingsberg

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

Department
The Department of Medicine, Huddinge, conducts preclinical and clinical research in a variety of areas and undergraduate and graduate education. The department is internationally oriented and consists of seven units with about 50 teams.

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.

Want to make a difference? Join us and contribute to better health for all

First day of employment according to agreement
Reference number STÖD 2-5087/2020
Contact
  • Assistant professor Mattias Carlsten, mattias.carlsten@ki.se
Union representative
  • Belinda Pannagel, SACO, Belinda.pannagel@ki.se
  • Christina Hammarstedt, OFR, Christina.hammarstedt@ki.se
Published 26.Nov.2020
Last application date 16.Dec.2020 11:59 PM CET

Return to job vacancies