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During my post-doc I explored the molecular mechanisms that drive cancer cell survival under challenging environmental conditions, such as low oxygen (hypoxia). Since hypoxia is a major cause of cancer therapy resistance, targeting the hypoxic parts of tumours is a promising strategy to improve the treatment response. I have described the transcriptional response of the tumour suppressor gene TP53 to hypoxic stress and the mechanisms of hypoxia-induced p53-dependent apoptosis (Leszczynska et al, 2015 JCI, Olcina et al, 2016 Oncogene). I have also investigated other aspect of hypoxia-induced DNA damage response (Leszczynska et al., 2016, Sci Rep). My work on testing an ATR inhibitor in oesophagal cancer supported the clinical trial, CHARIOT, on the dose escalation safety when combining the ATR inhibitor VX-970 with chemoradiotherapy in oesophagal cancer (EudraCT number: 2015-003965-27, Leszczynska et al, 2016 Radiother. Oncol). Since hypoxia is a major concern in the therapy resistance of glioblastoma, as a member of the Molecular Neurobiology Group at the Nencki Institute in Warsaw I am investigating the role of hypoxia in glioma-immune cells cross-communication and hypoxia-induced chromatin alterations. I am also interested in chromatin regulation in response to epigenetic treatments in pediatric high-grade gliomas.
Biography:
2006, MSc in Biotechnology at the Wroclaw University of Technology in Poland in 2006
2006-2007, work placement at Chembiotech, UK (sponsored by Leonardo da Vinci EU Grant)
2007-2011, PhD in Biomedical Research, University of Birmingham, UK; Investigation of the signalling and function of small Rho GTPases in angiogenesis;
2011, short post-doc at the Dunn School of Pathology, University of Oxford, UK; Signalling in the early embryo development;
2011-2018, post-doc at the CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, UK; Investigating hypoxia-induced DNA damage response in cancer therapy;
2019-present, post-doc at the Nencki Institue of Experimental Biology, Warsaw; The role of hypoxia in chromatin alterations of tumor microenvironment of glioblastoma; Epigenetic regulation of pediatric high-grade gliomas.
Grants (Principal Investigator on the grants):
2020-2023, Grant OPUS17 ( 2019/33/B/NZ1/01556) from the National Science Centre on „Regulation of chromatin accessibility in the hypoxic tumour microenvironment of glioblastoma”
2017 – 2018, Returning Carers’ Fund from the University of Oxford to support the project on hypoxia-activated p53-dependent targets
2015 – 2016, Early Stage Career Researcher Development Fund from the CRUK Oxford Centre to support preliminary work on hypoxia-activated p53-dependent targets and their role in stem cells
2006, Leonardo da Vinci Grant from the European Union fund, to fund a postgraduate placement in a company abroad (within EU). The award was used at Chembiotech Ltd, Birmingham
Awards:
2016, Award of Excellence from the Department of Oncology, University of Oxford
2015, European Association for Cancer Research (EACR) Meeting Bursary award and a runner up for the GRK Young Investigator Award at the Radiation Biology & Cancer Conference, Essen, Germany
2015, the best post-doc poster award at the Post-Doc Away Day, Department of Oncology, Oxford
2014, the best post-doc poster award at the Oxford Cancer Research Centre Symposium, Oxford
2012, The British Association for Cancer Research (BACR) / Hamilton-Fairley Young Investigator Award at the National Cancer Research Institute (NCRI) Conference, Liverpool
2010, Gordon Research Conference bursary award, the Endothelial Cell Phenotypes in Health & Disease Conference, Maine, USA
2010, BACR travel grant to attend the Gordon Research Conference on Endothelial Cell Phenotypes in Health & Disease, Maine, USA
2010, University of Birmingham bursary award to attend The Cell-Matrix Research Conference in Manchester
Selected publications:
Ramachandran S, Ma TS, Griffin J, Ng N, Foskolou IP, Hwang MS, Victori P, Cheng WC, Buffa FM, Leszczynska KB, El-Khamisy SF, Gromak M & Hammond EM „Hypoxia-induced SETX links replication stress with the unfolded protein response.” Nature Communications. Jun 17;12(1):3686, 2021
Bowler E, Skwarska A, Wilson JD, Ramachandran S, Bolland H, Easton A, Ostheimer C, Hwang MS, Leszczynska KB, Conway SJ and Hammond EM. “Pharmacological inhibition of ATR can block autophagy through an ATR-independent mechanism.” iScience, 23(11):101668, 2020
Göttgens EL, Bussink J, Leszczynska KB, Peters H, Span PN, Hammond EM. “Inhibition of CD4/CDK6 enhances radiosensitivity of HPV negative head and neck squamous cell carcinomas.” Int J Radiat Oncol Biol Phys. pii: S0360-3016(19)33419-4., 2019
Foskolou IP, Jorgensen C, Leszczynska KB, Olcina MM, Tarhonskaya H, Haisma B, D’Angiolella VD, Myers WK, Domene C, Flashman E and Hammnd EM. “Ribonucleotide reductase requires subunit switching in hypoxia to maintain DNA replication”. Mol Cell. 66(2):206-220.e9, 2017
Leszczynska KB, Dobrynin G, Ient J, Boumelha AJ, Senra JM, Hawkins MA, Maughan T, Mukherjee S and Hammond EM. “Preclinical testing of an ATR inhibitor demonstrates improved response to standard therapies for esophageal cancer”. Radiother Oncol. 121(2):232-238, 2016
Leszczynska KB, Göttgens EL, Biasoli D, Olcina MM, Ient J, Anbalagan S, Bernhardt S, Giaccia AJ and Hammond EM. “Mechanisms and consequences of ATMIN repression in hypoxic conditions: roles for p53 and HIF-1”. Sci Rep. 15;6:21698, 2016
Olcina MM, Leszczynska KB, Senra JM, Isa NF and Hammond EM. “Increased H3K9me3 facilitates p53-dependent apoptosis through repression of APAK in hypoxia”. Oncogene, 35(6):793-9, 2016
Leszczynska KB, Foskolou I, Abraham AG, Anbalagan S, Tellier C, Haider S, Span PN, O’Neill E, Buffa FM and Hammond EM. “Hypoxia-induced p53 modulates both apoptosis and radiosensitivity via AKT”. J Clin Invest. 125(6):2385-98, 2015
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