Daniela Zisterer
Associate Professor
School of Biochemistry and Immunology
Trinity College Dublin
Ireland
Biography
Daniela Zisterer has been a Lecturer in the School of Biochemistry and Immunology in Trinity College Dublin, since 2001. She was made a TCD Fellow and a Senior Lecturer in 2007. She is also a graduate of Trinity. She is currently the Coordinator of the Moderatorship in Biochemistry with Cell Biology. Her main research programme seeks to understand the molecular mechanisms underlying apoptotic cell death and how deregulated apoptosis leads to cancer. She is currently involved in developing novel anti-cancer agents with a number of international research collaborators. One of her ongoing projects is the development of a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds as potential anti-cancer agents. She has identified that these PBOX compounds potently induce apoptotic cell death in many resistant human cancer cells while eliciting minimal toxicity on normal cells and she has recently been granted a patent for their use as anti-cancer agents. She is the author of over 50 publications in some of the best international scientific journals including Cancer Research, the Journal of Pharmacology and Experimental Therapeutics, Molecular Pharmacology and the Journal of Biological Chemistry. Her research is supported by Science Foundation Ireland, Enterprise Ireland, the Health Research Board and the Children's Leukaemia Research Project.
Research Interest
Our research interests centres around the field of apoptosis and development of novel anti-cancer agents. Specifically we are developing a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds as potential anti-cancer agents. These compounds potently induce apoptotic cell death in many resistant human cancer cell lines in vitro such as chronic myeloid leukaemia cells. They also induce apoptosis in ex vivo patient samples such as B-Chronic Lymphocytic Leukaemia samples, while eliciting minimal toxicity on normal bone marrow cells. Furthermore, they exhibit anti-tumour properties in vivo, in a breast carcinoma tumour model that has been developed in the lab. This suggests the potential of these drugs as novel anti-cancer therapeutics in the treatment of both solid tumours and haematopoietic tumours. We have thus patented these compounds and have synthesised, screened and identified lead pro-apoptotic PBOX compounds. Current on-going investigations are seeking to characterise the molecular mechanisms by which these drugs induce apoptosis of cancerous cells. We have recently identified tubulin as the molecular target of the PBOX compounds. Our studies have demonstrated that PBOX compounds cause a depolymerisation of the microtubule network of cancer cells. They also cause a disassembly of purified tubulin in vitro. We are currently attempting to characterise the PBOX binding site on tubulin. Related studies in the lab involve evaluating the PBOX compounds as anti-angiogenic agents as compounds that target the microtubule cytoskeleton are known to interfere with angiogenic processes. Through collaboration, we are also developing other anti-cancer agents including a series of novel anti-estrogenic compounds and combretastatin A4 analogues.
Publications
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Pollock,Jade K. J.K., Verma,Navin Kumar N.K., O Boyle,Niamh M. N.M., Carr,Miriam G. M.G., Meegan,Mary Jane M.J., Zisterer,Daniela M. D.M., Combretastatin (CA)-4 and its novel analogue CA-432 impair T-cell migration through the Rho/ROCK signalling pathway, Biochemical Pharmacology, 92, (4), 2014, p544-557
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Niamh M. O Boyle, Jade K. Pollock, Miriam Carr, Andrew J. S. Knox, Seema M. Nathwani, Shu Wang, Laura Caboni, Daniela M. Zisterer, and Mary J. Meegan, β-Lactam Estrogen Receptor Antagonists and a Dual-Targeting Estrogen Receptor/Tubulin Ligand, Journal of Medicinal Chemistry, 57, (22), 2014, p9370 - 9382
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Lennon JC, Bright SA, Carroll E, Butini S, Campiani G, O Meara A, Williams DC, Zisterer DM, The novel pyrrolo-1,5-benzoxazepine, PBOX-6, synergistically enhances the apoptotic effects of carboplatin in drug sensitive and multidrug resistant neuroblastoma cells., Biochemical pharmacology, 87, (4), 2014, p611-24
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Spallarossa A, Caneva C, Caviglia M, Alfei S, Butini S, Campiani G, Gemma S, Brindisi M, Zisterer DM, Bright SA, Williams CD, Crespan E, Maga G, Sanna G, Delogu I, Collu G, Loddo R, Unconventional Knoevenagel-type indoles: Synthesis and cell-based studies for the identification of pro-apoptotic agents., European journal of medicinal chemistry, 102, 2015, p648-60
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Greene LM, Meegan MJ, Zisterer DM, Combretastatins: More Than Just Vascular Targeting Agents?, The Journal of pharmacology and experimental therapeutics, 355, (2), 2015, p212-27
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O Callaghan K, Palagano E, Butini S, Campiani G, Williams DC, Zisterer DM, O Sullivan J, Induction of apoptosis in oral squamous carcinoma cells by pyrrolo-1,5-benzoxazepines., Molecular medicine reports, 12, (3), 2015, p3748-54
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Kinsella P, Greene LM, Bright SA, Pollock JK, Butini S, Campiani G, Bauer S, Williams DC, Zisterer DM, The novel pyrrolo-1,5-benzoxazepine, PBOX-15, synergistically enhances the apoptotic efficacy of imatinib in gastrointestinal stromal tumours; suggested mechanism of action of PBOX-15., Investigational new drugs, 34, (2), 2016, 159-167
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Greene LM, Nathwani SM, Zisterer DM., Inhibition of γ-secretase activity synergistically enhances tumour necrosis factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute lymphoblastic leukemia cells via upregulation of death receptor 5., Oncology Letters, 12, (4), 2016, p2900 - 2905
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Carr M, Knox AJ, Lloyd DG, Zisterer DM, Meegan MJ., Development of the β-lactam type molecular scaffold for selective estrogen receptor α modulator action: synthesis and cytotoxic effects in MCF-7 breast cancer cells., Journal of Enzyme Inhibition and Medicinal Chemistry, 31, 2016, p117-130
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Kelly PM, Bright SA, Fayne D, Pollock JK, Zisterer DM, Williams DC, Meegan MJ, Synthesis, antiproliferative and pro-apoptotic activity of 2-phenylindoles., Bioorganic & medicinal chemistry, 24, (18), 2016, p4075-99 ,
