Angelica Squarzoni

Angelica Squarzoni was born in Italy in 1997. In 2019 she received a bachelor degree in Biological Sciences at the University of Ferrara, Italy. In 2021 she received the master degree in Health Biology at Alma Mater Studiorum – University of Bologna, Italy. During her master thesis she identified de novo variants in families with at least one subject affected by Autism Spectrum Disorders (ASD), learning new skills in DNA and RNA extraction from blood and saliva samples and learning how to execute PCR and Sanger sequencing.
In November 2021 she started her PhD course in Experimental Neuroscience at the University of Milano-Bicocca (Monza, Italy), under the supervision of Professor Arianna Scuteri, PhD. Currently, she is working on her PhD thesis, focusing on the identification of a possible synergistic effect between oxaliplatin and histone acetylation inhibitors as a protection against neurotoxicity and malignancies. During her PhD, she gained skills in cell biology (cancer cell lines and primary neurons), protein, DNA and RNA extraction, western blot, ELISAs, immunofluorescence and cell viability experiments.
In 2023 she visited the State University of New York (SUNY) at Buffalo (U.S.A.) as a visiting PhD student, in the research group of Professor Donald E. Mager, PharmD, PhD. There, she carried out both dry and wet lab experiments, focusing her abroad research period in learning new skills for in silico analysis and molecular modeling.

PhD research project

Identification of the possible neuro effects of HDACi on CIPN: in vitro and in vivo models

This project’s focuses on the improvement of anticancer therapy by two strategies: i) the optimization and the strengthening of the co-treatment with paclitaxel/oxaliplatin and HDACi; and ii) the identification of a possible neuroprotective effect of HDACi, to alleviate the neurotoxic side effects of different antineoplastic drugs in patients. Chemotherapy-induced peripheral neuropathy (CIPN) is a condition that affect patients treated with chemotherapy’s drugs, which main symptoms are pain and numbness in hands and feet. Present therapies aren’t suitable for a complete recovery and new treatments are currently studied [1].

Chemotherapy-induced cognitive impairment (CICI) is a condition, commonly reported in patients treated with chemotherapy’s drugs, in which patients show reduced mental ability, with weakened memory and executive function [2]. Both CIPN and CICI could have long-term effects on patients [2], [3]. Histone deacetylase inhibitors (HDACi) are a group of drugs that inhibit lysine’s deacetylation provided by HDAC [4], [5], limiting the expression of target genes and regulating cell’s metabolism. From the first approved HDACi, others had been approved or are currently tested for cancer’s treatment [4]. HDACi had also been tested for the treatment of nervous system’s damage, even the one caused by chemotherapy’s drugs ([6]–[8]). Moreover, a possible neuroprotective effect for HDACi drugs had been proposed [6].

During the first year, different lines of breast (MCF7, MDA-MB-231, HCC1937) and colorectal (HT-29, HCT-15, CaCo2) cancer cells will be screened in vitro against a panel of HDACi, to identify their antineoplastic effect. The specificity of HDACi will be assessed through tests on different non-cancerous human cell lines. The second year of this project is going to be focused on the optimization of the combination of HDACi and paclitaxel/oxaliplatin in the cancer cell lines used during the first year. Co-action’s tests of drug and HDACi will be executed in order to explore their combined effect on cancer cells. The third year of the project is going to be focused on the identification and test of the drug/HDACi combination into an in vivo model of CIPN and CICI.

References:

[1] A. Scuteri e G. Cavaletti, «How can neuroplasticity be utilized to improve neuropathy symptoms?», Expert Rev. Neurother., vol. 16, n. 11, pagg. 1235–1236, nov. 2016, doi: 10.1080/14737175.2016.1221344.

[2] A. A. Argyriou, K. Assimakopoulos, G. Iconomou, F. Giannakopoulou, e H. P. Kalofonos, «Either Called “Chemobrain” or “Chemofog,” the Long-Term Chemotherapy-Induced Cognitive Decline in Cancer Survivors Is Real», J. Pain Symptom Manage., vol. 41, n. 1, pagg. 126–139, gen. 2011, doi: 10.1016/j.jpainsymman.2010.04.021.

[3] C. S. Bonhof, L. V. van de Poll-Franse, D. K. Wasowicz, L. V. Beerepoot, G. Vreugdenhil, e F. Mols, «The course of peripheral neuropathy and its association with health-related quality of life among colorectal cancer patients», J. Cancer Surviv., vol. 15, n. 2, pagg. 190–200, apr. 2021, doi: 10.1007/s11764-020-00923-6.

[4] T. C. S. Ho, A. H. Y. Chan, e A. Ganesan, «Thirty Years of HDAC Inhibitors: 2020 Insight and Hindsight», J. Med. Chem., vol. 63, n. 21, pagg. 12460–12484, nov. 2020, doi: 10.1021/acs.jmedchem.0c00830.

[5] J. King, M. Patel, e S. Chandrasekaran, «Metabolism, HDACs, and HDAC Inhibitors: A Systems Biology Perspective», Metabolites, vol. 11, n. 11, pag. 792, nov. 2021, doi: 10.3390/metabo11110792.

[6] D. Wang, B. Wang, Y. Liu, X. Dong, Y. Su, e S. Li, «Protective Effects of ACY-1215 Against Chemotherapy-Related Cognitive Impairment and Brain Damage in Mice», Neurochem. Res., vol. 44, n. 11, pagg. 2460–2469, nov. 2019, doi: 10.1007/s11064-019-02882-6.

[7] J. Ma, X. Huo, M. B. Jarpe, A. Kavelaars, e C. J. Heijnen, «Pharmacological inhibition of HDAC6 reverses cognitive impairment and tau pathology as a result of cisplatin treatment», Acta Neuropathol. Commun., vol. 6, n. 1, pag. 103, dic. 2018, doi: 10.1186/s40478-018-0604-3.

[8] L. Van Helleputte et al., «Inhibition of histone deacetylase 6 (HDAC6) protects against vincristine-induced peripheral neuropathies and inhibits tumor growth», Neurobiol. Dis., vol. 111, pagg. 59–69, mar. 2018, doi: 10.1016/j.nbd.2017.11.011.