Stem Cell Ageing and Cancer
Dr Kristina Kirschner
- Honorary Senior Lecturer (School of Cancer Sciences)
email:
Kristina.Kirschner@glasgow.ac.uk
Beatson Institute for Cancer Research/ Institute of Cancer, Switchback Road, G61 1BD
Biography
I am Senior Lecturer/Associate Professor in the School of Cancer Sciences and the CRUK Beatson Institute, University of Glasgow, U.K., with an interest in hematopoietic stem cell ageing, consequences on immune cell composition and senescence alongside age-associated clonal haemopoiesis on a functional, metabolic, and transcriptional level. We recently paved the way towards a predictor for clonal haematopoiesis outcomes by following the Lothian Birth cohort participants longitudinally over 15 years, showing that gene-specific fitness can outweigh inter-individual variability (Robertson et al 2022 Nature Medicine, Robertson et al Current Biology 2019). Moreover, we demonstrated functional diversity in senescence using single cell RNA-sequencing approaches. We show that primary and secondary senescence are distinct molecular endpoints with a blunted secretory phenotype and the induction of fibrillar collagens in secondary senescence pointing towards functional diversification (Teo et al 2019, Cell Reports).
I also lead the Single Cell Advanced Technologies facility at the School of Cancer Sciences, University of Glasgow.
I obtained my Ph.D. from the University of Edinburgh, characterising one of the first DNA damage-dependent premature ageing mouse models (Kirschner et al. DNA repair 2007, AntiCancer Res 2010). During my post-doc at the CRUK Cambridge Institute, I revealed previously unanticipated levels of complexity in p53’s response to stress, identifying specific transcriptional patterns in senescence (Kirschner et al. PLOS Genetics 2015). Seeking a more readily translatable disease model and appreciating the pioneering history of leukaemia studies for understanding cancer I joined Prof. Anthony Green’s lab at the University of Cambridge. Ageing is the biggest single cause for cancer, and I therefore combined my expertise in ageing and cancer leading the way in identifying JAK/STAT driven transcriptional clonal haemopoiesis by single cell RNA-seq (Kirschner et al. 2017 Cell Rep). I was also the experimental lead to develop now widely used tool for single cell RNA-seq data analysis (Kiselev, Kirschner et al, Nat Methods 2017).
Research interests
Kristina is interested in the interplay between stem cell ageing and cancer, using a variety of model systems.
Current research themes are:
- Elucidating metabolic vulnerabilities in HSCs from in myeloproliferative disease (Ph.D. student)
- 2. Age-related clonal haemopoiesis in the Lothian Birth Cohorts (Ph.D. student)
We combine single cell omics and metabolomics approaches to interrogate properties of haematopoietic stem cells in vitro and in vivo in myeloproliferative disease context.
Clonal hematopoiesis of indeterminate potential (CHIP) in healthy individuals increases rapidly from age 60 onwards and has been associated with increased risk for malignancy. CHIP is driven by somatic mutations in stem cells that are implicated in leukemia. We elucidate differences in stem cell fitness caused by different mutations on the molecular and functional level in vitro and in vivo.
- 3. Tumour microenvironment in acute lymphoblastic leukaemia (post-doc)
- 4. Pathways to senescence heterogeneity (Ph.D. student)
Our overarching purpose is to understand better how stromal cells influence and are influenced by cancer cells. We interrogate the relationship between cancer-associated fibroblasts from bone marrow mesenchymal stromal cells and acute lymphoblastic leukaemia in vitro and in vivo.
By using co-culture in vitro approaches and advanced mouse models of secondary senescence, we aim to define molecular signatures of primary and secondary senescence.
- Senescence heterogeneity in liver cancer (Ph.D. student)
We investigate the role of stromal cell primary and secondary senescence in liver cancer initiation, progression and resistance to chemotherapy in the context of therapy induced senescence using single cell omics approaches, in vitro co-culture models and advanced mouse models.
Research groups
- Cancer Evolution in Time & Space
Grants
Grants and Awards listed are those received whilst working with the University of Glasgow.
- Engineering the bone marrow niche to control stem cell regulation, metastaticevolution and cancer dormancy
Engineering and Physical Sciences Research Council
2023 - 2028
- Mechanobiology-based medicine - Phase 2
Engineering and Physical Sciences Research Council
2023 - 2028
- Functional insights into clonal heamtopiesis mutations.
European Hematology Association
2023 - 2025
- Accurate molecular and phenotypic characterisation of gene-specific effects in longitudinal samples of CHIP
Blood Cancer UK
2023 - 2026
- Integrated analysis from mouse to man for Early detection of Mesothelioma.
Cancer Research UK
2022 - 2027
- Mechanobiology-based medicine
Engineering and Physical Sciences Research Council
2021 - 2022
- How do senescent stromal cells subvert the treatment response in acute lymphoblastic leukaemia?
Medical Research Council
2021 - 2024
- Dissecting innate immune determinants of severity and resolution in a longitudinal study of COVID-19
UK Research and Innovation
2020 - 2022
- Identifying metabolic vulnerabilities in patients with myeloproliferative neoplasms
NHS Greater Glasgow and Clyde Endowment Funds
2020 - 2021
- Single cell transcriptome and protein BM niche profiling with CITE-seq in CML disease progression
NHS Greater Glasgow and Clyde Endowment Funds
2020 - 2021
- What is the role of secondary senescence in disease? Elucidating the role of notch signalling in secondary senescence
Academy of Medical Sciences
2020 - 2022
- Early detection of pre-leukaemic clones in the aged haematopoietic compartment using single cell approaches
Leuka
2019 - 2021
- Elucidating metabolomics changes in myeloproliferative neoplasms
Tenovus Scotland
2019 - 2020
- heterotypic intercellular ERBB signalling in early progression of KRAS LuAd
Cancer Research UK
2019 - 2022
- Defining Epigenetic age as a novel tool for cancer grading
NHS Greater Glasgow and Clyde
2019 - 2019
- Eradication of the Leukaemic Clone in Myeloproliferative Neoplasms
University of Manchester
2018 - 2022
- Support for Epigenetics research
Medical Research Council
2017 - 2017
- Fellowship Award:Elucidating the response of the aged transcriptome and genome to oncogenic stress in haematopoietic stem cells using single cell approaches
Wellcome Trust
2016 - 2018
Supervision
Kristina currently supervises Ph.D. students and M.Sc. students in the lab.
Teaching
Kristina currently teaches on the M.Sc. Cancer Research & Precision Oncology programme.