Dr. Tony Mc Elligott

Summary

Chronic Lymphocytic leukaemia (CLL) is an incurable B-lymphoid malignancy accounting for 38% of leukaemias in the western world. CLL has a variable clinical course due differences in underlying genetic lesions, degree of clonal evolution, activated signalling pathways and interaction with the microenvironment within lymph nodes and the bone marrow. The aim of this project is to assess the functional impact of NOTCH1 mutations in CLL by utilizing in vitro micro-environment models to analyse aberrant signalling pathways in NOTCH1 mutated cells, allowing the determination of potential 'precision medicine' strategies for these patients.

Funding Agency

Wellcome Trust

Programme

ISSF Award

Summary

Multiple myeloma is a plasma cell malignancy that accounts for around 10% of all haematological cancers. It remains generally incurable, with most patients experiencing relapse after first-line treatment. In the EU, MM incidence is projected to increase from 35,000 new cases per annum to over 43,000 by 2030 whilst deaths due to MM are also projected to increase. Therefore new drugs are urgently required to improve the anti-myeloma arsenal. Aberrant activation of a number of oncogenic signalling pathways in myeloma leads to cell growth and survival, as well as to angiogenesis and to the development of drug resistance. Targeting one or more of these pathways is therefore a promising anti-MM strategy. We have recently designed and synthesized novel guanidinium compounds which have demonstrated anti-tumour activity in myeloma. A lead compound VP79s has been identified and its ability to induce apoptosis and to target oncogenic signalling pathways in MM including the STAT3 pathway has been examined. VP79s potently reduced the viability of drug resistant and sensitive MM cell lines through induction of apoptosis. Importantly, VP79s rapidly inhibited both constitutive and IL-6 induced STAT3 activation and, consequently, decreased expression of STAT3-mediated anti-apoptotic gene products, Mcl-1 and survivin. In conclusion, the novel compound VP79s can target dysregulated STAT3 activation and induce apoptosis in myeloma cells in vitro, suggesting its potential as a novel anti-cancer therapeutic which can overcome tumour microenvironment induced resistance. Identification and development of novel drugs that can target STAT3 remains an important scientific and clinical challenge.

Funding Agency

Trinity College

Programme

John Scott Fellowship

Project Type

Student Bursary

Person Months

42

Summary

Blood Cancer Network Ireland (BCNI) is a national clinical research network that benefits blood cancer patients in Ireland. BCNI offers early stage clinical trials to blood cancer patients, a biobank of blood cancer patient material and a blood cancer registry. This biobank of clinically and molecularly annotated patient material (RNA, DNA and cryopreserved cells) allows us to perform high quality clinical and translational research and allows us to collaborate with groups investigating novel therapeutic agents and immunotherapy strategies.

Funding Agency

SFI/Irish Cancer Society

Summary

Fungal secondary metabolites represent a diverse array of natural products, and bioactive compounds from these organisms have yielded some of the most important natural products for the pharmaceutical industry. Genome sequencing projects have revealed that fungi are rich in biosynthethic clusters that direct the synthesis of these secondary metabolites. R. emersonii is a thermophilic ascomycete that represents a reservoir of undiscovered bioactive compounds. This project seeks to investigate the therapeutic potential of secondary metabolites isolated from R. emersonii. A two-pronged approach will be adopted, employing functional genomics and a laboratory scale screening programme. Initially, the project is designed as a two year master's programme. However, given the huge diversity and structural types of known fungal secondary metabolites and the fact that more and more are continually being discovered, it is highly likely that R. emersonii will produce an array of secondary metabolite products. Thus, the potential for this project to continue to a PhD programme is extremely promising.

Funding Agency

IT Sligo

Programme

CUA Bursary Fund 2019

Project Type

Student Bursary

Person Months

24

Summary

In recent years, as part of engaging with patients and the public, it has become clear that patients want to know more about the research their samples were used for. Our cancer research community in Trinity College and St. James's Hospital are keen to inform and educate patients who have donated to the biobanks about the research conducted as well as informing cancer patients and the public about the benefits of participation in research, making them more likely to participate in the future. Our proposal is to unite our local biobanks to organise a novel annual cancer biobank awareness day. We are in the process of updating biobank patient information leaflets (PIL) and intend to include a web address for biobank updates and details of ongoing studies as well as details of the annual event. Details about the day will also be advertised in the hospital and an information desk will be set up in the main campus in the weeks running up to the event. Currently we are part of a national biobanking working group and it is hoped to expand this event to a national event in the future. This Project won Non-Pharmaceutical Eduaction Project of the Year at the 2021 Irish Healthcare Awards.

Funding Agency

Irish Cancer Society

Programme

Cancer Research Engagement Awards 2019

Person Months

12