Stem Cell Ageing and Cancer

CRUK Beatson Institute - Stem Cell Ageing and Cancer

Dr Kristina Kirschner

  • Senior Lecturer (Paul O'Gorman Leukaemia Research Centre)

Biography

Kristina received her Ph.D. from the University of Edinburgh characterising one of the first premature ageing mouse models. Her interest in ageing and cancer continued throughout her postdoc at the CRUK Cambridge Institute and at the Department of Haematology at the University of Cambridge, where she worked on the functional genomics of p53 in senescence and on haematopoietic stem cell ageing using single cell approaches. Kristina recently moved to the Institute of Cancer Sciences at the University of Glasgow, continuing her work in age-related haematopoietic stem cell heterogeneity and clonal hameopoiesis as a junior group leader. Another focus in the lab continues to be senescence heterogeneity. Kristina also runs the single cell advanced technologies for the Institute of Cancer Sciences.

LEUKA John Goldman Fellow 2019-2021

https://www.leuka.org.uk/research/leuka-funded-research/research-other-blood-cancers/early-detection-blood-cancers-elderly/

EHA-ASH TRTH Training Fellowship 2018

Lab page: https://www.gla.ac.uk/researchinstitutes/cancersciences/research/units/paulogormanleukaemiaresearchcentre/kkirschner/

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 heterogeneity in the ageing haematopoietic stem cell compartment

We combine single cell omics and metabolomics approaches to interrogate properties of aged haematopoietic stem cells in vitro and in vivo in normal haemopoiesis and myeloproliferative disease context.

- Exploring secondary senescence pathways in vitro and in vivo

By using co-culture in vitro approaches and advanced mouse models of secondary senescence, we aim to define functional differences between primary and secondary senescence.

Publications

List by: Type | Date

Jump to: 2022 | 2021 | 2020 | 2019 | 2018 | 2017 | 2016 | 2015 | 2013 | 2012 | 2010 | 2009 | 2007 | 2003
Number of items: 27.

2022

Kapeni, C. et al. (2022) p57Kip2 regulates embryonic blood stem cells by controlling sympathoadrenal progenitor expansion. Blood, (doi: 10.1182/blood.2021014853) (PMID:35653588) (Early Online Publication)

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)

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(1), 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 Tue Jun 28 05:44:03 2022 BST.
Jump to: Articles | Book Sections
Number of items: 27.

Articles

Kapeni, C. et al. (2022) p57Kip2 regulates embryonic blood stem cells by controlling sympathoadrenal progenitor expansion. Blood, (doi: 10.1182/blood.2021014853) (PMID:35653588) (Early Online Publication)

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)

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(1), 241. (doi: 10.1038/s41467-020-20378-8) (PMID:33431824) (PMCID:PMC7801601)

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)

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)

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. 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)

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)

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)

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)

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)

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)

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)

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)

Book Sections

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)

This list was generated on Tue Jun 28 05:44:03 2022 BST.

Grants

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • 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. 

Research datasets

Jump to: 2019 | 2017 | 2016 | 2015
Number of items: 5.

2019

Chandra, T., Rattanavirotkul, N. and Kirschner, K. (2019) Notch signalling mediates secondary senescence- imaging data. [Data Collection]

2017

Kirschner, K. and Green, A. (2017) Single Cell RNA-Sequencing using smart-seq2 of young and old murine hematopoietic stem cells. [Data Collection]

Kirschner, K. and Green, A. (2017) Gene expression profiling upon TPO treatment. [Data Collection]

2016

Green, A. and Kirschner, K. (2016) SC3-consensus clustering of single cell RNA-Seq data. [Data Collection]

2015

Kirschner, K. , Samarajiwa, S. and Menon, S. (2015) Phenotype specific analyses of p53 reveal distinct regulatory mechanism for chronically activated p53. [Data Collection]

This list was generated on Mon Jun 27 06:34:49 2022 BST.