Doctoral (PhD) student position in cancer immunotherapy

Do you want to contribute to improving human health?

To be a doctoral student means to devote oneself to a research project under supervision of experienced researchers and following an individual study plan. For a doctoral degree, the equivalent of four years of full-time doctoral education is required.

The research group

Associate Professor Dr Mattias Carlsten M.D. Ph.D. is heading a translational research group at Karolinska Institutet (KI) with close connection to the medical unit Cell Therapy and Allogeneic Stem Cell Transplantation (CAST) at the Karolinska University Hospital. The group is located at the Division of Biomolecular and Cellular Medicine (BCM) at the Department of Laboratory Medicine (Labmed, KI, http://ki.se). The main research focus of Associate Professor Carlsten’s group (https://ki.se/en/medh/mattias-carlsten-group)  is to study how NK cells can be utilized to treat cancer (Sanz Ortega et al. Leukemia, 2024, Segerberg et al. HemaSphere 2023, Björklund, Carlsten, Sohlberg et al. Clin. Can. Research 2018, Childs et al. Nature Reviews Drug Discovery 2015). More specifically, the group focuses its work around understanding basic biology and how to genetically engineer NK cells to improve their in vivo persistence and homing to the tumor for enhanced anti-tumor efficacy. Linked to this program, the group is also developing methods to dynamically track adoptively infused cells in vivo. As a physician-scientist, Associate Professor Carlsten’s work bridges pre-clinical in vitro studies to clinical exploration, from molecular and cellular biology via animal models to the development of early clinical trials on cellular cancer immunotherapy and gene therapy. As part of the overall vision, the group is now exploring the potential of CRISPR-based methods to improve the anti-tumor capacity of NK cells and how such approach can be used for in vivo editing. This will be done in close collaboration with Dr Laura Sanz Ortega in the Carlsten group as well as with Professor Samir EL Andaloussi at BCM, Labmed, KI (https://ki.se/en/research/research-areas-centres-and-networks/research-groups/biomolecular-medicine-and-advanced-therapies-focus-on-delivery-of-rna-therapeutics-research-group-samir-el-andaloussi) and Assistant Professor Joel Nordin at BCM, Labmed, KI (https://ki.se/en/research/research-areas-centres-and-networks/research-groups/research-group-joel-nordin#tab-start).

The doctoral student project and the duties of the doctoral student

Key factors identified to limit the success of adoptive NK cell cancer immunotherapy are the inability of the infused cells to persist home and to the tumor. Data also suggest that intratumoral factors can hamper the anti-tumor efficacy of NK cells. In addition to the above, the introduction of chimeric antigen receptors (CARs) hold promise to potentiate the NK cells. This project will focus on the development of CRISPR-based approaches to genetically introduce or remove molecules/elements that overall can augment the anti-tumor potential of NK cells. Optimization of newly developed methods to introduce these CRISPR-based principles via in vivo editing will be done in parallel. The overall goal is to establish proof-of-concept for in vivo editing of NK cells for augmented anti-tumor efficacy for deeper and durable responses. As part of the project, the student will address the role of introducing CARs and supporting cytokines and/or synthetic molecules via homology-directed end joining (HDR) for redirected tumor cell targeting and to promote in vivo persistence. Base-editing will also be used by the student to circumvent negatively impacting signals within the tumor microenvironment to further improve their efficacy. NK cell survival and tumor targeting after adoptive transfer will be addressed in xenogeneic animal models. Designing and cloning of gene constructs and guides will be a central part of the project. The project will also involve an array of other cellular and molecular biology techniques and assays such as flow cytometry, electroporation, ELISA etc. along with advanced methods of analysis. The position provides an exciting opportunity for the successful candidate to apply and develop cutting-edge technology and excel in the space between bench work, animal work and clinical studies with the overall aim of establishing new concepts to improve the therapeutic efficacy of NK cell-based cancer immunotherapy. As the supervisor constellation and their respective groups have complementary expertise and insights stretching from advanced CRISPR-based gene editing techniques and in vivo cargo delivery via genetic engineering and exploration of NK cells the cancer potential in vitro and in animal models to early phase clinical trials on cellular immunotherapy, the student will have the chance to learn cutting-edge technologies and get support all the way from the bench to the bedside. The supervisors expect a dedicated student with a burning interest in gaining new insights into how immune cells can be manipulated and utilized for enhanced therapeutic features. To succeed with this prospective wet lab PhD project, the student will be required to work actively in the laboratory in addition to data analysis, manuscript writing, and attending seminars, group meetings and the mandatory doctoral training courses.

What do we offer?

A creative and inspiring environment full of expertise and curiosity. Karolinska Institutet is one of the world's leading medical universities. Our vision is to pursue the development of knowledge about life and to promote a better health for all. At Karolinska Institutet, we conduct successful medical research and hold the largest range of medical education in Sweden. As a doctoral student you are offered an individual research project, a well-educated supervisor, a vast range of elective courses and the opportunity to work in a leading research group. Karolinska Institutet collaborates with prominent universities from all around the world, which ensures opportunities for international exchanges. You will be employed on a doctoral studentship which means that you receive a contractual salary. Employees also have access to our modern gym for free and receive reimbursements for medical care.

Eligibility requirements for doctoral education

In order to participate in the selection for a doctoral position, you must meet the following general (A) and specific (B) eligibility requirements at latest by the application deadline.

It is your responsibility to certify eligibility by following the instructions on the web page Entry requirements (eligibility) for doctoral education.

A) General eligibility requirement

You meet the general eligibility requirement for doctoral/third-cycle/PhD education if you:

1. have been awarded a second-cycle/advanced/master qualification (i.e. master degree), or
2. have satisfied the requirements for courses comprising at least 240 credits of which at least 60 credits were awarded in the advanced/second-cycle/master level, or
3. have acquired substantially equivalent knowledge in some other way in Sweden or abroad.*

Follow the instructions on the web page Entry requirements (eligibility) for doctoral education.

*If you claim equivalent knowledge, follow the instructions on the web page Assessing equivalent knowledge for general eligibility for doctoral education.

B) Specific eligibility requirement

You meet the specific eligibility requirement for doctoral/third-cycle/PhD education if you:

- Show proficiency in English equivalent to the course English B/English 6 at Swedish upper secondary school.

Follow the instructions on the web page English language requirements for doctoral education.

Verification of your documents Karolinska Institutet checks the authenticity of your documents. Karolinska Institutet reserves the right to revoke admission if supporting documents are discovered to be fraudulent. Submission of false documents is a violation of Swedish law and is considered grounds for legal action.

(A) and (B) can only be certified by the documentation requirement for doctoral education.

Skills and personal qualities

We are seeking a highly talented and enthusiastic individual who holds a Medical Doctor degree with experience of working as a physician at a cell and/or gene therapy clinical unit, but who also has basic laboratory experience. The student should have a background in immunology and cell signaling. Know-how in running immunology assays and conducting cell culture work are critical merits, while experience in cloning and work related to genetic manipulation and use of such (in cells and/or animals) will be considered as assets. State-of-the-art knowledge and hands-on experience in multiparameter flow cytometry and subsequent analysis together with mastering Western Blot and PCR-based methods are requirements. Credentials (i.e. FELSA) and proficiency in working with mice is essential. Insights of the process to translate new ideas to clinical exploration and understanding of clinical trial protocols for cancer therapy is strongly preferable. Experience from other research environments and a track-record of being supervisor of intern/master students as well as clinical students are together with a documented participation in courses relevant for the topic of this PhD considered a plus.

The successful candidate should have excellent interpersonal and communication skills, organizational skills, and the ability to work productively and dynamically in a team while actively interacting with several research groups. 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.

Terms and conditions

The doctoral student will be employed on a doctoral studentship maximum 4 years full-time.

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Application process

Submit your application and supporting documents through the Varbi recruitment system. Use the button in the top right corner and follow the instructions. We prefer that your application is written in English, but you can also apply in Swedish.

Your application must contain the following documents:

- A personal letter and a curriculum vitae
- Degree projects and previous publications, if any
- Any other documentation showing the desirable skills and personal qualities described above
- Documents certifying your general eligibility (see A above)
- Documents certifying your specific eligibility (see B above)

Selection

A selection will be made among eligible applicants on the basis of the ability to benefit from doctoral education. The qualifications of the applicants will be evaluated on an overall basis.

Karolinska Institutet uses the following bases of assessment:

- Documented subject knowledge of relevance to the area of research
- Analytical skill
- Other documented knowledge or experience that may be relevant to doctoral studies in the subject.

All applicants will be informed when the recruitment is completed.

Cancer immunotherapy – Mattias Carlsten group 

Biomolecular Medicine and Advanced therapies- focus on delivery of RNA therapeutics – Research group Samir EL Andaloussi 

Research group Joel Nordin

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