Radiotherapy is an essential and highly effective part of the treatment of many cancers, including paediatric and adult brain tumours. Irradiation of normal brain tissue is, however, unavoidable and can result in major impairments of neurocognitive functioning and reduced quality of life. Similar effects occur after chemotherapy for brain and non-intracranial tumours.
Lara Barazzuol’s group focuses on assessing the effect of radiation (and chemotherapy) on the brain and aims to achieve an improved biological and molecular understanding of cancer treatment-induced neurocognitive dysfunction.
All Publications: mepa page
- Barazzuol L, Hopkins SR, Ju L, Jeggo PA. Distinct response of adult neural stem cells to low versus high dose ionising radiation. DNA Repair 2019 76:70-75. Pdf.
- Barazzuol L, Ju L, Jeggo PA. A coordinated DNA damage response promotes adult quiescent neural stem cell activation PLOS Biology 2017; https://doi.org/10.1371/journal.pbio.2001264. Pdf
- Barazzuol L, Ju L, Jeggo PA. In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation. Journal of Radiation Research 2016 1:i2-i10. Pdf
- Barazzuol L, Rickett N, Ju L, Jeggo PA. Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells Journal of Cell Science 2015 128(19):3597-606. Pdf
- Saha S, Woodbine L, Haines J, Coster M, Ricket N, Barazzuol L, Ainsbury E, Sienkiewicz Z, Jeggo P. Increased apoptosis and DNA double-strand breaks in the embryonic mouse brain in response to very low-dose X-rays but not 50 Hz magnetic fields Journal of the Royal Society Interface 2014 11(100):20140783. Pdf
- Barazzuol L, Jeynes JC, Merchant MJ, Wéra AC, Barry M, Kirkby KJ, Suzuki M. Radiosensitisation of glioblastoma cells using a histone deacetylase inhibitor (SAHA) comparing carbon ions with X-rays. International Journal of Radiation Biology 2015 91(1):90-8. Pdf
- Wéra AC, Barazzuol L, Jeynes JC, Merchant MJ, Suzuki M, Kirkby KJ. Influence of the nucleus area distribution on the survival fraction after charged particles broad beam irradiation. Physics in Medicine & Biology 2014 59 4197. Pdf
- Barazzuol L, Jena R, Burnet NG, Jeynes JCG, Kirkby KJ, Kirkby NF. Evaluation of poly(ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma. Radiation Oncology 2013 8:65. Pdf
- Barazzuol L, Jena R, Burnet NG, Jeynes JCG, Merchant MJ, Kirkby KJ, Kirkby NF. In vitro evaluation of combined temozolomide and radiotherapy using X-rays and high linear energy transfer radiation for glioblastoma. Radiation Research 2012 177:651-662. Pdf
- Barazzuol L, Burnet NG, Jena R, Jones B, Jefferies SJ, Kirkby NF. A mathematical model of brain tumour response to radiotherapy and chemotherapy considering radiobiological aspects Journal of Theoretical Biology 2010 262(3):553-65. Pdf
When using radiotherapy in the treatment of primary and metastatic brain tumours, damage of normal brain tissue is an unavoidable side effect. This can severely compromise cancer patients’ quality of life by diminishing their neurocognitive function, especially in cases of childhood brain tumours. The underlying mechanisms are not fully understood and, at present, there is no effective treatment.
Lara Barazzuol’s lab, by using a combination of methodologies (ranging from brain organoids, bioinformatics, in vivo imaging and behavioural tests), aims to understand the underlying biological and molecular mechanisms of radiotherapy-induced neurocognitive dysfunction; and, to elucidate the effect of genetic variation on the pattern and severity of neurocognitive outcome based on clinical data.
Another interest of Lara Barazzuol’s lab is investigating how defects in DNA repair impact on human health, with a particular focus on neurodegenerative diseases, and understanding how this knowledge can be exploited in the clinic.
Selected ongoing projects/grants:
KWF high risk project: Targeting protein aggregation to ameliorate radiotherapy-induced neurocognitive dysfunction.
KWF Young Investigator project: Preventing radiation-induced neurocognitive dysfunction in patients with paediatric brain tumours: biological mechanisms and potential role of proton therapy.
ZonMw Off-Road project: An improved understanding of radiotherapy-induced neurocognitive decline: biological mechanisms and treatment potential.
Projects for internships of Master’s and technical students are available in the following topics:
- Investigating the response of radiation or chemotherapy-induced DNA damage on human brain organoids
- Investigating the role of DNA damage-induced protein aggregation, senescence and immune response in neurocognitive dysfunction
- Further development and characterization of our human brain organoid system
- Analysis of behavioural data and PET neuroimaging after radiation damage
We are currently looking for an enthusiastic Postdoc to work on protein homeostasis and cancer treatment-induced neurocognitive dysfunction. Deadline 15 September 2019. For further details and how to apply: http://bit.ly/2KsIdzP.