Miss Daniella di Mascio MSc

Postgraduate Research Student in DNA–small molecule interactions

Daniella di Mascio is a Postgraduate Research Student working on the interactions small molecules with DNA within Biological Sciences at the University of Southampton.

Academic qualifications

2017-present: PhD Research Student in Biological Sciences, University of Southampton, UK.
2013-2017: Masters in Biochemistry, University of Southampton, UK.

Research

Publications

Teaching

Contact

Research interests

My research focuses on the interaction of novel minor groove binding agents with DNA, with a specific focus on the binding of pyrrolobenzodizipines (PBDs) to DNA. PBDs are a class of naturally occurring molecules and due to their interaction with DNA they have the potential to be used as anti-cancer agents. The PBD core structure can be extensively modified and my research aims to look at how these modifications can influence and improve their interactivity and binding properties with DNA.

Supervisor: Professor Keith Fox
PhD Research: DNA Interactivity with Novel Minor Groove Binding Agents
Funding: Femtogenix

Research group

Molecular and Cellular Biosciences

Research project(s)

DNA sequence recognition by small molecules

We are using the footprinting technique with natural and synthetic DNA substrates to study the sequence selectivity of novel DNA binding small molecules.

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Article

Fox, K. , Procopiou, G., Jackson, P. J. M., Auer, J. , Di Mascio, D. , Pepper, C., Miraz Rahman, K., & Thurston, D. E. (2022). DNA sequence-selective G-A cross-linking ADC payloads for use in solid tumour therapies . Communications Biology , 5 (741), 741. [741]. https://doi.org/Antibody-Drug Conjugates (ADCs) are growing in importance for the treatment of both solid and haematological malignancies. There is a demand for new payloads with novel mechanisms of action that may offer enhanced therapeutic efficacy, especially in patients who develop resistance. We report here a class of Cyclopropabenzindole-Pyridinobenzodiazepine (CBI-PDD) DNA cross-linking payloads that simultaneously alkylate guanine (G) and adenine (A) bases in the DNA minor groove with a defined sequence selectivity. The lead payload, FGX8-46 (6), produces sequence-selective G-A cross-links and affords cytotoxicity in the low picomolar region across a panel of 11 human tumour cell lines. When conjugated to the antibody cetuximab at an average Drug-Antibody Ratio (DAR) of 2, an ADC is produced with significant antitumour activity at 1 mg/kg in a target-relevant human tumour xenograft mouse model with an unexpectedly high tolerability (i.e., no weight loss observed at doses as high as 45 mg/kg i.v., single dose). , https://doi.org/10.1038/s42003-022-03633-0

Thesis

Di Mascio, D. (2022). The interaction of novel Pyrrolobenzodiazepine derivatives with DNA . University of Southampton.

Demonstrator

BIOL2010 The Flow of Genetic Information

Miss Daniella di Mascio
School of Biological Sciences
Faculty of Environmental and Life Sciences
Life Sciences Building 85
University of Southampton
Highfield Campus
Southampton
SO17 1BJ

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