Staff Profile
Dr Sara Luzzi
Research Associate
- Email: sara.luzzi@ncl.ac.uk
- Address: Newcastle University Biosciences Institute
International Centre for Life, East Wing
Central Parkway
Newcastle upon Tyne, NE1 3BZ
United Kingdom
Part of the Biosciences Institute, the Cells, Genes and Molecules Theme and the Vascular Biology and Medicine Theme
Member the NUBI RA committee and the FMS postdoc committee. Former member of the CBCC Researchers' committee.
Research Experience
Postdoctoral Research Associate, Newcastle University (United Kingdom), February 2020 - present
Postdoctoral Research Associate, Newcastle University (United Kingdom), July 2019 - December 2019
PhD student, Newcastle University (United Kingdom), March 2016 - June 2019
Research Assistant, Institut Curie (France), October 2014 - February 2016
Postgraduate student, Sapienza University (Italy), September 2012 - September 2014
Undergraduate student, Sapienza University (Italy), April 2012 - July 2012
Grants and awards
BSCB/CoB Travel Award, January 2024
Newcastle University Faculty of Medical Sciences Research Excellence Development Award, October 2023
BBSRC Responsive Mode Research Grant (Co-investigator), August 2021
JGW Patterson Foundation Research Grant (Co-awardee), May 2020
Newcastle University Research Travel Fund, February 2019
Post-submission PhD Scholarship, February 2019
Newcastle University PhD Studentship, September 2015
Education
2019 - PhD, Cell and Molecular Biosciences, Newcastle University (United Kingdom)
2014 - Master's, Genetics and Molecular Biology, Sapienza University (Italy)
2012 - BSc, Biological Sciences, Sapienza University (Italy)
Social media
CURRENT RESEARCH INTERESTS
Control of 3'-end formation in human breast cancer cells
Proper maturation of the 3' terminus of messenger RNAs (mRNAs) is essential to ensure functional gene expression. Most eukaryotes employ alternative polyadenylation (APA) to increase the number of RNA isoforms transcribed from one gene, thus allowing not only production of different proteins but also tissue-specific diversification of the protein function. However, aberrant APA leads to disruption of gene expression with severe consequences on genome stability, and can cause human disease and cancer. I am studying the mechanisms regulated by RNA binding proteins and chromatin modifications that prevent aberrant APA in breast cancer cells, which can help identify possible therapeutic targets for breast cancer treatment/prevention.
Funders: JGW Patterson Foundation, BBSRC (co-investigator)
RNA binding proteins in male germ cell development
RNA splicing plays an essential role in spermatogenesis, and mutations within genes that encode for splicing regulators have been associated with male infertility. Some RNA binding proteins that control splicing during spermatogenesis are only expressed in the testis, and derive from X-linked genes via retrotransposition. These factors have probably evolved to replace the function of their X-linked mother genes, which get inactivated during male meiosis through a process called meiotic sex chromosome inactivation (MSCI). Part of my research looks at the conservation between an X-linked gene and its meiotic-specific retrogene in splicing regulation (currently available as Reviewed Preprint on eLife, https://elifesciences.org/reviewed-preprints/89705), and at the implications in male fertility.
Funder: BBSRC (co-investigator)
Hormone-dependent alternative splicing in breast and prostate cancer
Breast and prostate cancer are amongst the most frequent types of cancers in the UK and worldwide. Initially these cancers strongly depend on hormones to grow, so a common treatment is endocrine therapy. Nevertheless, patients often relapse because the cancer becomes resistant to this type of therapy and likely to metastasise. I have recently found that different stages of cancer express alternative versions of an important splicing factor implicated in epithelial-mesenchymal transitions, a process that promotes metastasis. Abundance of these alternative proteins depends on hormones in both breast and prostate cancer cells, and could have different impact on cancer metastasis.
Funder: Newcastle University FMS Research Excellence Development Award
Regulation of transcriptional pausing by RNA binding proteins in breast cancer cells
Transcription across most human genes is generally paused near the start, both to allow quality control of the newly synthesised RNA and to regulate transcription levels. Disruption of this pathway has been linked to human disease and cancer. Several protein factors with a known role in cancer biology have been identified as regulators of transcription pausing (including c-myc). My research characterises a possible role for oncogenic RNA binding proteins in this process, and understand their contribution to cancer progression and metastasis.
Funder: JGW Patterson Foundation (co-awardee)
PREVIOUS RESEARCH INTERESTS
Chromatin regulation of transcription in the budding yeast Saccharomyces cerevisiae
During my PhD under the supervision of Dr Manolis Papamichos-Chronakis I described a mechanism of RNA quality control through premature transcription termination that depends on the chromatin remodeller INO80. A preprint of this study is currently deposited on biorXiv.
Funder: Newcastle University
Integrity of human telomeres upon exposure to X-radiation
During my BSc and Master's I analysed the effects of X-radiation on human telomere length and integrity, cellular senescence and apoptosis. Furthermore, I found that the coenzyme Q10 has a role in protecting human telomeres from radiation-induced DNA damage. Part of my findings were published in Microgravity Science and Technology
Funder: ASI (Italian Space Agency)
Teacher for BGM3063 (Biochemistry of Gene Expression) - 2021 to present
Lab supervision of undergraduate students (2nd and 3rd stage) and postgraduate students (including PhD) - 2016 to present
Lab demonstrator - 2018
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Articles
- Adamson B, Brittain N, Walker L, Duncan R, Luzzi S, Rescigno P, Smith GR, McGill S, Burchmore RJ, Willmore E, Hickson I, Robson CN, Bogdan D, Jimenez-Vacas JM, Paschalis A, Welti J, Yuan W, McCracken SR, Heer R, Sharp A, de Bono J, Gaughan L. The catalytic subunit of DNA-PK regulates transcription and splicing of AR in advanced prostate cancer. The Journal of Clinical Investigation 2023, 133(22), e169200.
- Siachisumo C*, Luzzi S*, Aldalaqan S*, Hysenaj G, Dalgliesh C, Cheung K, Gazzara M, Yonchev ID, James K, Kheirollahi Chadegani M, Ehrmann I, Smith GR, Cockell SJ, Munkley J, Barash Y, Wilson SA, Elliott DJ. An anciently diverged family of RNA binding proteins maintain correct splicing of a class of ultra-long exons through cryptic splice site repression. eLife 2024, 12, RP89705.
- Luzzi S, Szachnowski U, Greener S, Gautier C, Han KH, Darke J, Piccinno R, Lafon A, Pugh BF, Morillon A, Papamichos-Chronakis M. The INO80 remodeler couples premature termination of mRNA synthesis with transcription elongation. bioRxiv 2020.
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Reviews
- Advani R, Luzzi S, Scott E, Dalgliesh C, Weischenfeldt J, Munkley J, Elliott DJ. Epithelial specific splicing regulator proteins as emerging oncogenes in aggressive prostate cancer. Oncogene 2023, 42, 3161–3168.
- Aldalaqan S, Dalgliesh C, Luzzi S, Siachisumo C, Reynard LN, Ehrmann I, Elliott DJ. Cryptic splicing: common pathological mechanisms involved in male infertility and neuronal diseases. Cell Cycle 2022, 21(3), 219-227.