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

Publications

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Jump to: 2024 | 2023 | 2022 | 2021 | 2020 | 2019 | 2018 | 2017 | 2016 | 2015 | 2013 | 2012 | 2010 | 2009 | 2007 | 2003

Number of items: 42.

2024

Kiourtis, C. et al. (2024) Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ. Nature Cell Biology, (doi: 10.1038/s41556-024-01543-3) (PMID:39537753) (Early Online Publication)

Burt, R. J. et al. (2024) Mitochondrial dsRNA from B-ALL cells stimulates mesenchymal stromal cells to become cancer-associated fibroblasts. Blood Advances, 8(21), pp. 5696-5709. (PMID:39226456)

Dawson, A. et al. (2024) Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nature Communications, 15, 1090. (doi: 10.1038/s41467-024-45471-0) (PMID:38316788) (PMCID:PMC10844594)

Fetit, R. et al. (2024) Characterising neutrophil subtypes in cancer using scRNA sequencing demonstrates the importance of IL-1β/CXCR2 axis in generation of metastasis specific neutrophils. Cancer Research Communications, 4(2), pp. 588-606. (doi: 10.1158/2767-9764.CRC-23-0319) (PMID:38358352) (PMCID:PMC10903300)

2023

Zarou, M. M. et al. (2023) Leukaemia Exposure Alters the Transcriptional Profile and Function of Macrophages in the Bone Marrow Niche. 65th ASH Annual Meeting and Exposition, San Diego, California, USA, 09-12 Dec 2023. (doi: 10.1182/blood-2023-181630)

Vande Voorde, J. et al. (2023) Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target. Nature Metabolism, 5(8), pp. 1303-1318. (doi: 10.1038/s42255-023-00857-0) (PMID:37580540) (PMCID:PMC10447251)

Yang, F., Nourse, C., Helgason, G. V. and Kirschner, K. (2023) Unraveling heterogeneity in the aging hematopoietic stem cell compartment: an insight from single-cell approaches. HemaSphere, 7(6), e895. (doi: 10.1097/hs9.0000000000000895) (PMID:37304939) (PMCID:PMC10256339)

O’Sullivan, E. D. et al. (2023) Indian Hedgehog release from TNF activated renal epithelia drives local and remote organ fibrosis. Science Translational Medicine, 15(698), eabn07. (doi: 10.1126/scitranslmed.abn0736) (PMID:37256934)

Pearson, S., Blance, R., Yan, F., Hsieh, Y.-C., Geary, B., Amaral, F. M. R., Somervaille, T. C. P., Kirschner, K. , Whetton, A. D. and Pierce, A. (2023) Identification of curaxin as a potential new therapeutic for JAK2 V617F mutant patients. PLoS ONE, 18(5), e0286412. (doi: 10.1371/journal.pone.0286412) (PMID:37253035) (PMCID:PMC10228771)

Edwards, S. C. et al. (2023) PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A–producing γδ T cells. Journal of Experimental Medicine, 220(2), e20211431. (doi: 10.1084/jem.20211431) (PMID:36480166) (PMCID:PMC9732671)

2022

O’Sullivan, E. D. et al. (2022) Single-cell analysis of senescent epithelia reveals targetable mechanisms promoting fibrosis. JCI Insight, 7(22), e154124. (doi: 10.1172/jci.insight.154124) (PMID:36509292) (PMCID:PMC9746814)

Kapeni, C. et al. (2022) p57Kip2 regulates embryonic blood stem cells by controlling sympathoadrenal progenitor expansion. Blood, 140(5), pp. 464-477. (doi: 10.1182/blood.2021014853) (PMID:35653588)

Robertson, N. A. et al. (2022) Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects. Nature Medicine, 28(7), pp. 1439-1446. (doi: 10.1038/s41591-022-01883-3) (PMID:35788175) (PMCID:PMC9307482)

Kay, E. J. et al. (2022) Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. Nature Metabolism, 4(6), pp. 693-710. (doi: 10.1038/s42255-022-00582-0) (PMID:35760868) (PMCID:PMC9236907)

Tomimatsu, K. et al. (2022) Locus-specific induction of gene expression from heterochromatin loci during cellular senescence. Nature Aging, 2, pp. 31-45. (doi: 10.1038/s43587-021-00147-y)

2021

Flanagan, D. J. et al. (2021) NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. Nature, 594, pp. 430-435. (doi: 10.1038/s41586-021-03525-z) (PMID:34079124)

Hsieh, Y.-C., Kirschner, K. and Copland, M. (2021) Improving outcomes in chronic myeloid leukemia through harnessing the immunological landscape. Leukemia, 35(5), pp. 1229-1242. (doi: 10.1038/s41375-021-01238-w) (PMID:33833387) (PMCID:PMC8102187)

Mooney, L., Goodyear, C. S. , Chandra, T., Kirschner, K. , Copland, M. , Petrie, M. C. and Lang, N. N. (2021) Clonal haematopoiesis of indeterminate potential: intersections between inflammation, vascular disease and heart failure. Clinical Science, 135(7), pp. 991-1007. (doi: 10.1042/CS20200306) (PMID:33861346) (PMCID:PMC8055963)

Rattanavirotkul, N., Kirschner, K. and Chandra, T. (2021) Induction and transmission of oncogene-induced senescence. Cellular and Molecular Life Sciences, 78(3), pp. 843-852. (doi: 10.1007/s00018-020-03638-0) (PMID:32936311) (PMCID:PMC7897614)

Latif, A.-L. et al. (2021) BRD4-mediated repression of p53 is a target for combination therapy in AML. Nature Communications, 12, 241. (doi: 10.1038/s41467-020-20378-8) (PMID:33431824) (PMCID:PMC7801601)

2020

Crosse, E. I. et al. (2020) Multi-layered spatial transcriptomics identify secretory factors promoting human hematopoietic stem cell development. Cell Stem Cell, 27(5), 822-839.e8. (doi: 10.1016/j.stem.2020.08.004) (PMID:32946788) (PMCID:PMC7671940)

Alivernini, S. et al. (2020) Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nature Medicine, 26(8), pp. 1295-1306. (doi: 10.1038/s41591-020-0939-8) (PMID:32601335)

Terradas-Terradas, M. , Robertson, N. A., Chandra, T. and Kirschner, K. (2020) Clonality in haematopoietic stem cell ageing. Mechanisms of Ageing and Development, 189, 111279. (doi: 10.1016/j.mad.2020.111279) (PMID:32526214) (PMCID:PMC7347006)

Kirschner, K. , Rattanavirotkul, N., Quince, M. F. and Chandra, T. (2020) Functional heterogeneity in senescence. Biochemical Society Transactions, 48(3), pp. 765-773. (doi: 10.1042/BST20190109) (PMID:32369550) (PMCID:PMC7329341)

2019

Burt, R. et al. (2019) Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukaemia cells from oxidative stress. Blood, 134(17), pp. 1415-1429. (doi: 10.1182/blood.2019001398) (PMID:31501154) (PMCID:PMC6856969)

Robertson, N. A., Hillary, R. F., McCartney, D. L., Terradas-Terradas, M. , Higham, J., Sproul, D., Deary, I. J., Kirschner, K. , Marioni, R. E. and Chandra, T. (2019) Age-related clonal haemopoiesis is associated with increased epigenetic age. Current Biology, 29(16), R786-R787. (doi: 10.1016/j.cub.2019.07.011) (PMID:31430471)

Teo, Y. V. et al. (2019) Notch signaling mediates secondary senescence. Cell Reports, 27(4), 997-1007.e5. (doi: 10.1016/j.celrep.2019.03.104) (PMID:31018144) (PMCID:PMC6486482)

2018

Baran-Gale, J., Chandra, T. and Kirschner, K. (2018) Experimental design for single-cell RNA sequencing. Briefings in Functional Genomics, 17(4), pp. 233-239. (doi: 10.1093/bfgp/elx035) (PMID:29126257) (PMCID:PMC6063265)

Kirschner, K. , Krueger, F., Green, A. R. and Chandra, T. (2018) Multiplexing for oxidative bisulfite sequencing (oxBS-seq). In: Tost, J. (ed.) DNA Methylation Protocols. Series: Methods in molecular biology, 1708 (1708). Humana Press: New York, pp. 665-678. ISBN 9781493974795 (doi: 10.1007/978-1-4939-7481-8_34)

2017

Kirschner, K. et al. (2017) Proliferation drives aging-related functional decline in a subpopulation of the hematopoietic stem cell compartment. Cell Reports, 19(8), pp. 1503-1511. (doi: 10.1016/j.celrep.2017.04.074) (PMID:28538171) (PMCID:PMC5457484)

Kiselev, V. Y. et al. (2017) SC3: consensus clustering of single cell RNA-seq data. Nature Methods, 14(5), pp. 483-486. (doi: 10.1038/nmeth.4236) (PMID:28346451)

2016

Chandra, T. and Kirschner, K. (2016) Chromosome organisation during ageing and senescence. Current Opinion in Cell Biology, 40, pp. 161-167. (doi: 10.1016/j.ceb.2016.03.020) (PMID:27101466)

Park, H. J., Li, J., Hannah, R., Biddie, S., Leal‐Cervantes, A. I., Kirschner, K. , Flores Santa Cruz, D., Sexl, V., Göttgens, B. and Green, A. R. (2016) Cytokine‐induced megakaryocytic differentiation is regulated by genome‐wide loss of a uSTAT transcriptional program. EMBO Journal, 35(6), pp. 580-594. (doi: 10.15252/embj.201592383) (PMID:26702099) (PMCID:PMC4801948)

2015

Kirschner, K. et al. (2015) Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53. PLoS Genetics, 11(3), e1005053. (doi: 10.1371/journal.pgen.1005053) (PMID:25790137) (PMCID:PMC4366240)

Chandra, T., Ewels, P. A., Schoenfelder, S., Furlan-Magaril, M., Wingett, S. W., Kirschner, K. , Thuret, J.-Y., Andrews, S., Fraser, P. and Reik, W. (2015) Global reorganization of the nuclear landscape in senescent cells. Cell Reports, 10(4), pp. 471-483. (doi: 10.1016/j.celrep.2014.12.055) (PMID:25640177) (PMCID:PMC4542308)

2013

Kent, D. G. et al. (2013) Self-renewal of single mouse hematopoietic stem cells is reduced by JAK2V617F without compromising progenitor cell expansion. PLoS Biology, 11(6), e1001576. (doi: 10.1371/journal.pbio.1001576) (PMID:23750118) (PMCID:PMC3672217)

Ward, M. C. et al. (2013) Latent regulatory potential of human-specific repetitive elements. Molecular Cell, 49(2), pp. 262-272. (doi: 10.1016/j.molcel.2012.11.013) (PMID:23246434) (PMCID:PMC3560060)

2012

Chandra, T. et al. (2012) Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation. Molecular Cell, 47(2), pp. 203-214. (doi: 10.1016/j.molcel.2012.06.010) (PMID:22795131) (PMCID:PMC3701408)

2010

Kirschner, K. and Melton, D. W. (2010) Multiple roles of the ERCC1-XPF endonuclease in DNA repair and resistance to anticancer drugs. Anticancer Research, 30(9), pp. 3223-3232. (PMID:20944091)

2009

Young, A. R.J. et al. (2009) Autophagy mediates the mitotic senescence transition. Genes and Development, 23(7), pp. 798-803. (doi: 10.1101/gad.519709) (PMID:19279323) (PMCID:PMC2666340)

2007

Kirschner, K. , Singh, R., Prost, S. and Melton, D. W. (2007) Characterisation of Ercc1 deficiency in the liver and in conditional Ercc1-deficient primary hepatocytes in vitro. DNA Repair, 6(3), pp. 304-316. (doi: 10.1016/j.dnarep.2006.10.020) (PMID:17126084)

2003

Gunnarsson, C., Ahnström, M., Kirschner, K. , Olsson, B., Nordenskjöld, B., Rutqvist, L. E., Skoog, L. and Stål, O. (2003) Amplification of HSD17B1 and ERBB2 in primary breast cancer. Oncogene, 22(1), pp. 34-40. (doi: 10.1038/sj.onc.1206078) (PMID:12527905)

This list was generated on Sat Dec 21 21:43:21 2024 GMT.

Jump to: Articles | Book Sections | Conference or Workshop Item

Number of items: 42.

Articles

Burt, R. J. et al. (2024) Mitochondrial dsRNA from B-ALL cells stimulates mesenchymal stromal cells to become cancer-associated fibroblasts. Blood Advances, 8(21), pp. 5696-5709. (PMID:39226456)

Tomimatsu, K. et al. (2022) Locus-specific induction of gene expression from heterochromatin loci during cellular senescence. Nature Aging, 2, pp. 31-45. (doi: 10.1038/s43587-021-00147-y)

Flanagan, D. J. et al. (2021) NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. Nature, 594, pp. 430-435. (doi: 10.1038/s41586-021-03525-z) (PMID:34079124)

Teo, Y. V. et al. (2019) Notch signaling mediates secondary senescence. Cell Reports, 27(4), 997-1007.e5. (doi: 10.1016/j.celrep.2019.03.104) (PMID:31018144) (PMCID:PMC6486482)

Kiselev, V. Y. et al. (2017) SC3: consensus clustering of single cell RNA-seq data. Nature Methods, 14(5), pp. 483-486. (doi: 10.1038/nmeth.4236) (PMID:28346451)

Chandra, T. and Kirschner, K. (2016) Chromosome organisation during ageing and senescence. Current Opinion in Cell Biology, 40, pp. 161-167. (doi: 10.1016/j.ceb.2016.03.020) (PMID:27101466)

Kirschner, K. and Melton, D. W. (2010) Multiple roles of the ERCC1-XPF endonuclease in DNA repair and resistance to anticancer drugs. Anticancer Research, 30(9), pp. 3223-3232. (PMID:20944091)

Young, A. R.J. et al. (2009) Autophagy mediates the mitotic senescence transition. Genes and Development, 23(7), pp. 798-803. (doi: 10.1101/gad.519709) (PMID:19279323) (PMCID:PMC2666340)

Book Sections

Conference or Workshop Item

This list was generated on Sat Dec 21 21:43:21 2024 GMT.

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