About the Division of Therapeutic Immunology and Transfusion Medicine
Our group perform immunological research, mainly focusing on T cells. We work with all T cells but our main focus is unconventional T cells, especially γδ T cells, as these immune cells have not so far been efficiently exploited.
Using state-of-art methods we are looking into γδ T cell reconstitution, and how these cells are affected by different transplant related factors. We also aim to investigate the development and functionality of γδ T cells in detail after hematopoietic stem cell transplantation (HSCT). This could help pave the way for more advanced and targeted approaches in cancer immunotherapy and in infectious diseases, particularly in patients undergoing HSCT.
We also have projects focusing on tumor-infiltrating lymphocytes (TILs) in solid tumors, mainly in ovarian cancer and prostate cancer. We use cancer patient-derived material and isolate lymphocytes from peripheral blood, ascites and tumor which we use for projects involving the characterization and functionality of lymphocytes with emphasis on T-cells. Our aim is to increase the understanding of how the tumor microenvironment can alter the phenotype of TILs and their ability to function and eliminate tumor cells. By using different immunomodulatory approaches, including PD-1 blockade with novel constructs, we try to enhance the responsiveness of TILs ex vivo.
Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are diseases which require treatment with toxic chemotherapy or HSCT. A high burden of leukemic stem cells (LSCs) in AML/MDS patients is associated with high risk of relapse and death, making those cells a good target for new therapies. Bispecific T-cell (BITE) and NK-cell engagers (BIKE) are new classes of immunotherapeutic agents. Their structure and specificity allow them to link a T-/NK-cell to a tumor cell and thereby stimulating effector cell activation, tumor killing and cytokine production. One project within the group is focused on the design and characterization of a BITE and BIKE directed against the molecules expressed LSCs. Our BITE/BIKE would enable the redirection of the T-cell effector function towards malignant cells, directly targeting leukemic cancer cells. The specific depletion of LSCs in AML/MDS patients making the therapy more efficient and less toxic.
Michael obtained his Ph.D. from Karolinska Institutet 2006. 2012 he reached the level of associate professor in Immunology. Michael is employed by the Karolinska University Hospital where he is responsible for the section of Clinical Immunology at the department of Clinical Immunology and Transfusion medicine. Together with his research group he focus on T-cell Immunology and Immune Therapy.
Lisa-Mari MörkSenior lab manager
Lisa-Mari received her Ph.D. from Karolinska Institutet in 2010 with a project investigating cholesterol and bile acid metabolism in hepatocytes. After that she worked as a post doc and later on as a lab manager at the Liver Cell Lab, CLINTEC, with the main focus to use primary hepatocytes for cell transplantation in patients with metabolic diseases. She joined Michael Uhlin’ s group in 2017 and is working as a senior lab manager.
Lucas Coelho Marliere ArrudaPost doc
Lucas received his Pharm.D. from Ouro Preto Pharmacy School, Brazil, in 2011. His Ph.D. was obtained from University of São Paulo, Brazil, in 2017, where he worked with autologous hematopoietic stem cell transplantation to treat autoimmune disease patients. He joined Dr Uhlin´s lab in 2017 and has been working in the development and characterization of bispecific antibodies, specially T-cell and NK-cell engagers (BITE/BIKE), to treat leukemia (AML and MDS) patients.
Arwen StikvoortPost doc
Arwen received her Master’s degree in Bio-medical sciences from Leiden university, the Netherlands in 2012. Her Ph.D in Medicine was obtained at Karolinska Universitetet, Sweden in 2017. During her Ph.D Arwen’s research focused on the development and prediction of graft-versus-host disease and long-term hematopoietic mixed chimerism post hematopoietic stem cell transplantation. During a first Post doc position, she worked on the development of chimeric antigen receptor natural killer (CAR-NK) cells for the treatment of multiple myeloma at the Amsterdam UMC in the Netherlands.
Arwen then joined Professor Michael Uhlin’s lab in 2020 to work on the development of bispecific antibodies, especially NK-cell engagers (BIKE) to treat leukemia patients. Additionally, she will be working with tumor-infiltrating lymphocytes from human ovarian cancer patients with the aims to increase knowledge of the presence, phenotype and functionality of these T cells.
Eoghan O´LearyPost doc
Eoghan received his Master’s degree in Molecular Cell Biology from University College Cork, Ireland in 2018. His Ph.D in Molecular Biology and Genetics was obtained at Aarhus University, Denmark in 2022. During his Ph.D Eoghan’s research focused on exploring the biogenesis of a subset of RNAs characterised by their closed circular structure, known as circular RNAs. Eoghan’s research focused on investigating the contribution of RNA binding proteins in regulating circular RNA production. Eoghan joined Professor Michael Uhlin’s lab in 2022 in collaboration with the Norwegian Biotech company Targovax.
Ahmed GaballaPhD student
Ahmed has graduated from faculty of Medicine in 2007, and obtained a Master degree in Medical Biochemistry and Molecular Biology from Egypt in 2013. He started his doctoral program at Karolinska Institutet in 2015. The main aim of his project is to study γδ T cell reconstitution after allogeneic HSCT, and to understand how different transplant related factors affect it. In addition, he is also interested in studying the development and functionality of γδ T cells in detail after HSCT and their correlation to clinical outcome.
Tengyu WangPhD student
Tengyu studied medicine at Karolinska Institutet 2004 – 2010. He is currently working at the department of clinical immunology and transfusion medicine. The topic of his Ph.D. studies is apheresis techniques and markers of viability and function on stem cell grafts. These markers are then used to predict and to improve clinical outcomes for patients receiving allogeneic stem cell transplantations.
Linda LarssonPhD student
Linda has a Master’s degree in biochemistry and a Bachelor’s degree in sports medicine from Umeå University 2006, with complementary courses in immunology and transfusion medicine. Linda is a Technical Manager at the department of Clinical Immunology and Transfusion Medicine at Karolinska University Hospital, where she has specialized in blood component production since 2009. In 2017, she started her PhD degree education for Michael Uhlin. She focuses on red blood cell storage lesion during development of new production strategies for red blood cell components.
Faisal AlagrafiPhD Student
Faisal received his bachelor’s degree in Biochemistry in 2008 from King Saud University. In 2016, he completed his MSc degree of Science in Cell Biology, Genetics, and Histology at King Saud University with a study investigating the effect of extracts derived from Rhazya stricta species on human stem cell proliferation and differentiation. He joined Michael Uhlin’ s group as PhD student in 2020. His projects aim to in-depth characterize both phenotypic and functional changes of γδ T cells after hematopoietic stem cell transplantation (HSCT). He will also identify and explore the rare subsets of γδ T cells in transplant patients in long-term aspect using single cell isolation and sequencing technology.
Emelie FoordPhD student
Emelie is a biomedical scientist (BMA) and received her Master’s degree in biomedical laboratory science in 2014 from Karolinska Institutet after having done her bachelor and master thesis work under the supervision of Michael Uhlin with focus on immune reconstitution after allogeneic stem cell transplantation. She is currently a PhD student in the group and her research focuses on co-stimulation and co-inhibition of tumor-infiltrating lymphocytes in human solid tumors. She primarily works with primary cells from human ovarian cancer and this work aims to increase knowledge of the presence, phenotype and functionality of infiltrating T-cells and T-cell subsets, and ultimately ways to enhance the responsiveness of these cells.
Ulla Axdorph Nygell
Beatrice Diedrich Aspevall
Maria Kristina Kvist
Sara Lind Enoksson
Theresa Neimert Andersson
Ina Laura Pieper
Anna Cecilia Söderström
Main current funding
Characterization of ascites- and tumor-infiltrating γδ T cells reveals distinct repertoires and a beneficial role in ovarian cancer. Foord E, Arruda LCM, Gaballa A, Klynning C, Uhlin M. Science Translational Medicine. 2021 Jan 20;13(577):eabb0192. doi: 10.1126/scitranslmed.abb0192
DEHT is a suitable plasticizer option for phthalate-free storage of irradiated red blood cells. Larsson L, Ohlsson S, Derving J, Diedrich B, Sandgren P, Larsson S, Uhlin M. Vox Sang. 2021 Jul 15. doi: 10.1111/vox.13177.
Profound Functional Suppression of Tumor-Infiltrating T-Cells in Ovarian Cancer Patients Can Be Reversed Using PD-1-Blocking Antibodies or DARPin® Proteins. Foord E, Klynning C, Schoutrop E, Förster JM, Krieg J, Mörtberg A, Müller MR, Herzog C, Schiegg D, Villemagne D, Fiedler U, Snell D, Kebble B, Mattsson J, Levitsky V, Uhlin M. Journal of Immunololy Research. 2020 Aug 4;2020:7375947. doi: 10.1155/2020/7375947.
Impact of γδ T cells on clinical outcome of hematopoietic stem cell transplantation: systematic review and meta-analysis.Arruda LCM, Gaballa A, Uhlin M. Blood Adv. 2019 Nov 12;3(21):3436-3448. doi: 10.1182/bloodadvances.2019000682.PMID: 31714966
Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion. Rådestad E, Sundin M, Törlén J, Thunberg S, Önfelt B, Ljungman P, Watz E, Mattsson J, Uhlin M. Front Immunol. 2019 Feb 11;10:189. doi: 10.3389/fimmu.2019.00189. eCollection 2019. PMID:30804948
T-cell frequencies of CD8+ γδ and CD27+ γδ cells in the stem cell graft predict the outcome after allogeneic hematopoietic cell transplantation. Gaballa A, Stikvoort A, Önfelt B, Mattsson J, Sundin M, Watz E, Uhlin M. Bone Marrow Transplant. 2019 Oct;54(10):1562-1574. doi: 10.1038/s41409-019-0462-z.PMID:30723262
Graft γδ TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution. Arruda LCM, Gaballa A, Uhlin M. J Immunol. 2019 Mar 15;202(6):1859-1870. doi: 10.4049/jimmunol.1801448.PMID:30710048
Risk Factors for Severe Acute Graft-versus-Host Disease in Donor Graft Composition. Stikvoort A, Gaballa A, Solders M, Nederlof I, Önfelt B, Sundberg B, Remberger M, Sundin M, Mattsson J, Uhlin M. Biol Blood Marrow Transplant. 2018 Mar;24(3):467-477. doi: 10.1016/j.bbmt.2017.11.026.PMID: 29197674