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.
Voshart DC, Wiedemann J, van Luijk P*, Barazzuol L*. Regional responses in radiation-induced normal tissue damage. Cancers 2021; 13(3), 367. *Corresponding authors. PMID: 33498403. Pdf
Peng X, Wu Y, Brouwer U, van Vliet T, Wang B, Demaria M, Barazzuol L*, Coppes RP*. Cellular senescence contributes to radiation-induced hyposalivation by affecting the stem/progenitor cell niche. Cell Death Dis. 2020; 11:854. PMID: 33056980. *Corresponding authors. Pdf
Barazzuol L, Coppes RP, van Luijk P. Prevention and treatment of radiotherapy-induced side effects. Mol Oncol. 2020; 14(7),1538-1554. Pdf
Barazzuol L*, Hopkins SR, Limei J, Jeggo PA. Distinct response of adult neural stem cells to low versus high dose ionising radiation. DNA Repair 2019; 76, 70-75. PMID: 30822688. *Corresponding author. Pdf.
Barazzuol L, Ju L, Jeggo PA. A coordinated DNA damage response promotes adult quiescent neural stem cell activation. PLoS Biol. 2017; 15(5):e2001264. PMID: 28489848. Pdf
Barazzuol L, Jeggo PA. In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation. J Radiat Res. 2016; 1:i2-i10. PMID: 27125639. 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. J Cell Sci. 2015; 128(19):3597-606. PMID: 26303202. 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. J R Soc Interface 2014; 11(100):20140783. PMID:25209403. 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. Int J Radiat Biol 2015; 91(1):90-8. PMID:25040548. *Corresponding author. 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. Radiat Oncol 2013; 8:65. PMID:23510353. *Corresponding author. 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.
Stand Up To Cancer – Cancer Research UK: BRAINatomy: a validated anatomical atlas of childhood neuroradiation damage.
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 different models from brain organoids to brain tissues
Investigating the role of DNA damage-induced protein aggregation, senescence and immune response in neurocognitive dysfunction
Analysis and validation of RNA-seq data of brain cells and tissues after DNA damage
Analysis of behavioural data and PET neuroimaging after radiation-induced damage
Open application Internship form MCB section
Application form for an internship at one of the research groups of the section Medical Cell Biology of the department Biomedical Sciences of Cells and Systems