Doctoral Defence: Sofie Lundgren, Somatic mutations and aberrant immune responses in aplastic anemia
Before Sofie Lundgren started her MD/PhD studies at the University of Helsinki, a few landmark studies on clonal hematopoiesis had raised the question whether somatic mutations lead to other clinically relevant conditions besides malignancy. At the same time in Helsinki, prof. Satu Mustjoki was initiating projects characterizing somatic mutations in “benign” T cells. Inspired by STAT3 mutations in LGL leukemia, prof. Mustjoki wanted to investigate whether somatic mutations could promote abnormal T cell responses in a broader spectrum of autoimmune diseases.
Although Lundgren had no previous experience in T cells, autoimmune diseases, or hematology, she got interested in the hypothesis and stepped up. Lundgren’s projects were built around a fascinating model disease, aplastic anemia (AA), where the clonal evolution of hematopoietic stem cells is shaped by autoimmune attack from cytotoxic CD8+ T cells.
Lundgren will defend her PhD thesis “Somatic mutations and aberrant immune responses in aplastic anemia” on Friday August 23rd at noon in Meilahti Bridge Hospital, Lecture Hall Kruununhaka. The thesis focuses on cytotoxic lymphocytes driving abnormal immune responses in auto- and alloimmunity. The work was carried out at the Hematology Research Unit Helsinki (HRUH), Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center.
In her thesis, Lundgren showed that somatic driver mutations are ubiquitous in clonally expanded T cells, and the mutations commonly affect pathways crucial for T cell activation and survival. Although the longitudinal clonal structure and mutated T cell phenotype analyses are limited to a few index patients, the findings suggest that T cell fate and clonal expansion can be affected by somatic mutations.
Lundgren broadened her research to characterise the landscape of immune cells of patients with AA at single-cell level. Deep immune profiling revealed that innate and adaptive immune cells in AA bone marrow start to resemble each other. She showed that in addition to CD8+ T cells, NK cells are enriched in AA bone marrow microenvironment. Unsupervised clustering methods identified AA-related T cell receptor motifs, which could be further studied to find the currently unknown target antigens in AA.
During her deep dive into immunology and genetics, Lundgren was graduated as an MD. She has developed her clinical skills in Helsinki, Porvoo, and Kittilä, and wishes to continue her journey in both worlds.
iCAN wishes Sofie Lundgren all the best in the future endeavours!
What: Doctoral defence of Sofie Lundgren “Somatic mutations and aberrant immune responses in aplastic anemia”. The dissertation is available on Helda.
When: 23.8.2024 at 12
Where: Meilahti Bridge Hospital, Lecture Hall Kruununhaka, Haartmaninkatu 4.
Alternatively, you can follow the event online.
Opponent: Asst. Prof. Siddhartha Jaiswal, Stanford University
Custos: Professor Satu Mustjoki, University of Helsinki
Contact: sofie.lundgren@helsinki.fi
You are also welcome to iCAN science seminar on 22.8. with Lundgren’s opponent Asst. Prof. Siddhartha Jaiswal. Read more…