APOPTOSIS AND DEVELOPMENT OF NOVEL ANTI-CANCER DRUGS

Dr Daniela Zisterer

Daniela Zisterer B.A.(Mod.), Ph.D.
Phone: + 353-1-896-1628
Fax: + 353 - 1 - 6772400
Email: dzistrer@tcd.ie
Location: Room 6.06, Biomedical Sciences Institute

Research Interests

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.

Research Staff

Seema Nathwani (BSc. PhD)
Lisa Greene (BSc. PhD)
Sandra Bright (BA.Mod)

Research Collaborators

Prof Craig Jordan, Center for Human Genetics, Rochester Medical Center, New York, US .
Prof. Giuseppe Campiani, Dept. of Pharmaceutical Chemistry, University of Sienna, Italy.
Prof. Mark Lawler, Institute of Molecular Medicine , St James’s Hospital, Dublin.
Dr Margaret McGee, Conway Institute of Molecular & Biomedical Research, University College Dublin.
Dr. Mary Meegan, School of Pharmacy, Trinity College Dublin .
Dr David Lloyd, School of Biochemistry & Immunology, Trinity College Dublin.
Prof. Clive Williams, School of Biochemistry & Immunology, Trinity College Dublin.
Dr Amir Khan, School of Biochemistry & Immunology, Trinity College Dublin.

Recent Publications by the Apoptosis and Development of Novel Anti-Cancer Drugs Group

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