LDCRC UPDATE FEBRUARY 2023
It is now 15 months since we launched the LDCRC and we are incredibly proud of what we have achieved in that short time. We have attracted over 5 million euros in research funding and have published 15 articles. We are especially proud to publish two publications which are collaborative projects between LDCRC members (Clifford/Ryan, Jalali/Brown). With your continued energy, we hope to build on our seeds of success and grow cancer research through joint initiatives with UL and UHL with the goal of improving the lives of those who suffer from cancer.
We are excited to introduce you to Eimear Scully (Eimear.Scully@ul.ie), the new senior administrator of the LDCRC, please contact her with your news and updates, which we hope to provide in a monthly update to LDCRC members, collaborators, and friends in Limerick. We also hope to create a newsletter for national distribution to highlight our success to our national collaborators and partners.
Management Board (2021-2022)
Prof
Next Meeting
Please come to our next meeting at CERC, UHL, on Feb 7th 3-5pm
We will soon announce a more complete calendar of events and meetings. We have monthly subgroup meetings with clinical themes. We also have a bioinformatics and bio imaging group that meets in UL on the 1st and 3rd Wednesday at 1pm in Bernal Room MS2-014
These are all hybrid meetings, and we welcome attendees both in-person and on MS Teams. Eimear can send you the information.
Clinical Cancer Research Capacity
UL-UHL Clinical Partners
Increasing numbers of clinical colleagues are directly engaging with the LDCRC. Principal investigators for translational and interventional studies and UL collaborators include:
Prof Ruth Clifford, Consultant Haematologist, Cancer Research Lead UHL and Director of Cancer Clinical Trial Unit, Associate Clinical Professor, GEMS, Clinical lead for LDCRC
Mr Gregory Korpanty, Consultant Medical Oncologist, Adjunct Senior Lecturer, GEMS, Co-Director Cancer Clinical Trial Unit, UHL, Clinical Lead Lung Cancer subgroup
Mr Chwanrow Baban Consultant Breast Surgeon, Senior Lecturer and Module Lead for Surgery,GEMS. Clinical lead of the Breast cancer subgroup
Mr Colin Pierce, Consultant Colorectal Surgeon, Adjunct Senior Clinical Lecturer, GEMS, Clinical Lead for Colorectal Cancer subgroup
Dr Sinead Field, Consultant Dermatologist, Adjunct Senior Clinical Lecturer, GEMS, Clinical Lead for Skin Cancer subgroup
Dr Hilary O’ Leary, Consultant Haematologist, Associate Clinical Director, Diagnostics Directorate, Adjunct Senior Clinical Lecturer, GEMS, Lymphoma Lead
Dr Lorraine Walsh, Consultant Radiation Oncologist, Adjunct Senior Lecturer, GEMS, Lead for Radiotherapy research
Prof Jenny Ni Mhuircheartaigh, Consultant Radiologist, Professor of Radiology, SoM, Lead for AI projects in Multiple Myeloma
Prof Calvin Coffey, Consultant Colorectal Surgeon, Professor of Surgery SoM, Colorectal cancer research
Prof Shona Tormey, Consultant Breast Surgeon, Associate Clinical Professor, GEMS, Breast Cancer Research
UHL Patient Involvement
Lead by Miriam McCarthy, HSA Manager, along with haematologists Dr Mary Ryan and Prof Ruth Clifford, Fidelma Hackett Advanced Nurse Practitioner, and members of the UHL Patient Advocacy and Liaison Team (PALS) a group of patients with cancer form the Patient and Public Involvement in research group.
UL-UHL Clinical Working Groups
We have established working groups with involvement of multidisciplinary teams including scientists, nursing, medical, allied health professionals, informatics and patients in the following cancer areas:
PPI group – Lead Ms Miriam McCarthy
Lung Cancer - Scientific Lead; Dr Caitriona Dowling, Clinical Lead Dr Gregory Korpanty
Blood Cancer - Scientific Lead; Dr Elizabeth Ryan, Clinical Lead Prof Ruth Clifford
Colorectal Cancer - Scientific Lead; Dr Kieran McGrourty, Clinical Lead Mr Colin Pierce
Breast Cancer - Scientific Lead; Dr James Brown, Clinical Lead Mr Chwanrow Baban
Skin Cancer - Clinical Lead Dr Sinead Field, Scientific Lead TBC
Developing biobanking capabilities and clinical databasing is a key priority across the groups.
Cancer Clinical Trial Unit @UHL activity 2022
In the CCTU at UHL we have recruited 309 patients, both regulated and unregulated, over 2022. For regulated, interventional clinical trials we have recruited 47 patients to studies. The haematology portfolio has grown over an 18-month period driven by dedicated PIs with 5 Haematology consultants acting as PIs across all disease areas.
We have recruited 23 patients across 5 interventional clinical studies and 252 patients to observational and translational studies.
Limerick was the second highest recruiter nationally to the CLL17 international collaborative group Phase III interventional study, and the 4th highest recruiter internationally. This is coming from a situation devoid of interventional clinical studies in Haematology, from 2015 to 2021.
The ISA-RVD Multiple Myeloma study is recruiting well, and Limerick is the 2nd highest recruiter nationally.
Cancer Clinical Trials Unit, International Clinical Trials Day 2019
Limerick has a rapidly growing translational studies profile, and this is seen in the high numbers of patients recruited to both the BCBI biobanking study in CLL, AML and Myeloma (n=147) and also the COVID vaccine in CLL study with UL (n=75).
This year we are adding two Cancer-associated thromboses studies, led by PI Dr Denis O’ Keeffe, to our portfolio. Dr O’ Keeffe is a national leader in the field of thrombosis management and a top recruiter to the Tillery clinical trial (non-cancer study).
In addition, a basket Phase II interventional clinical trial in lymphoid malignancies is opening in Q1 2024, the first basket study in Haematology at UHL. We are also opening a Phase III study in Relapsed Multiple Myeloma in Q1-Q2 2024 acknowledging this gap in our portfolio.
The medical oncology portfolio is led by Dr Gregory Korpanty with subspeciality areas of lung cancer, colorectal cancer and melanoma. Working with the Cancer Directorate, the CCTU Management team has a strategic plan for long term sustainability of the Medical Oncology portfolio beginning with the appointment of 2 Medical Oncologists (currently advertised). One of these appointments has 0.2 WTE clinical research time. There is also a planned 0.2 WTE academic appointment with UL SoM. Currently we have 24 patients enrolled in regulated, interventional studies and 11 patients in an unregulated observational study. Targeting specific disease areas affecting many of our patients in the Mid-West such as breast cancer, lung cancer and colorectal cancer is the focus in Medical Oncology as we regrow the portfolio in a sustainable manner led by the co-director of the CCTU and Medical Oncology Lead, Dr Gregory Korpanty. Through the LDCRC we are expanding our translational research and areas such as breast, colorectal and radiotherapy studies are being evaluated.
Open Positions
Please share these with your network. We need to attract the most talented researchers Professor of Cancer Bioinformatics, School of Medicine, deadline Feb 13th Post Doctoral Researcher in Single Cell Bioinformatics (Culhane lab). School of Medicine, deadline Feb 28th
There will be an AICRI postdoctoral fellow and Prof Culhane has a number of positions for PhD students, postdocs and a software engineer that will be advertised shortly
News Coverage LDCRC in the media https://www.rte.ie/news/munster/2021/0923/1248590-cancer-research/
Events
Dr. Virag Sharma and Prof. Aedin Culhane co-hosted the All-Ireland Virtual Bioinformatics and Evolution meeting, July 2020 with >110 attendees. Prof Des Higgins, Ireland’s most cited scientist was the keynote speaker
Prof Aedin Culhane (UL) and Prof Mark Lawler (QUB) held an a hybrid workshop on digital health with the All-Ireland Cancer Research Institute in Dell on April, 29th 2022.
The Digital Health meeting was attended by over 30 people in person and over double that number online.
National and International leadership
The All-Ireland Cancer Research Institute (AICRI)
The LDCRC is a member of AICRI, the All-Ireland Cancer Research Institute which was recently funded (€4 million grant) under the HEA shared island awards. All partners including UL/UHL are awarded two positions in the AICRI_start project. This award is funding a PhD student (PI Catriona Dowling and Paul Murray) and Postdoc through the AICRI_start grant. The postdoc position is yet to be advertised. To learn more see https://research.ie/what-wedo/loveirishresearch/blog/project-spotlight-all-island-cancer-research-institute/
HSE National Genetics and Genomics Strategy
Prof Culhane provided advice to 2 working groups (Workforce & Training, Genomics Infrastructure) in the National Genetics & Genomics. The Strategy is available at https://www.hse.ie/eng/about/who/strategic-programmes-office-overview/national-strategyfor-accelerating-genetic-and-genomic-medicine-in-ireland/national-strategy-for-acceleratinggenetic-and-genomic-medicine-in-ireland.pdf
Membership of ELIXIR
ELIXIR is an EU umbrella organization that connects EU bioinformatics. Prof Denis Shields (UCD) leads the Irish nodes. UCD, UG and UCD are members and RSCI and UL are onboarding sites onto the Irish node.
National Spatial Profiling Platform
The National Spatial Tissue Profiling (NaSPro) Platform for Precision Medicine: Integration of Chemical, Brightfield and Fluorescence Imaging of Tissues Combined with Single Cell Molecular Profiling NaSPro integrates advanced technology platforms in relation to spatial profiling of complex tissues across four sites, namely University of Limerick (UL), University College Dublin (UCD), the Royal College of Surgeons in Ireland (RCSI) and Technological University Dublin (TU Dublin). Awarded €2.25 Million in funding from Science Foundation Ireland under its 2021
Research Infrastructure Programme, the NaSPro technology platform is particularly useful for assessing tissues which have been stored for many years in histopathology laboratories, by providing new ways of exploring these tissues at a single cell level. It is also particularly useful in biomedical research projects which involve trying to understand why certain tissues are different than others, e.g. normal from cancer tissues, or drug-treated from control.
The NaSPro Platform provides a unique Ireland-wide capability in the integrated spatial profiling of complex tissues and 3D cellular/biological constructs. The platform is accessible to all researchers across Ireland.
Platforms and Points of Contact
DEPArray Plus, Leica Bond RXm, Ion Torrent Sequencer
University of Limerick
Prof. Paul Murray or Dr Eanna Fennel Email: Paul.Murray@ul.ie
Vectra Polaris and Proxima and Next Seq 2000 Sequencing System
University College Dublin
Prof. William Gallagher Email: william.gallagher@ucd.ie
Cell Dive Spatial Proteomics, Leica Bond RXm with Robotics and HALO
Royal College of Surgeons in Ireland
Prof. Jochen Prehn Email: JPrehn@rcsi.ie
Spero-QT-340 QCL-FTIR Imaging Spectrometer
Technological University Dublin
Dr. Aidan Meade Email: aidan.meade@tudublin.ie
Genomics Data Infrastructure for the European 1 million Genomes Project
The LDCRC will play a significant role in establishing the technical infrastructure to support the GDI European project that will support the integration of genomics into healthcare and advance new treatments for patients. Jointly funded by the European Commission, under the Digital Europe Programme, and the Health Research Board (HRB), Genomic Data Infrastructure (GDI) Ireland is part of a consortium of 20 EU Member States with the goal of enabling access to genomics and corresponding clinical data across Europe by creating secure data infrastructure. The project will facilitate a cross-border federated network of national genome collections for biomedical research and personalised medicine solutions. Prof Aedín Culhane explained that this project has the potential to provide countless future benefits to health.
“It will provide access to EU clinical genomics data. This is especially important for rare genetic diseases in small countries like Ireland. Access to larger pools of data will help doctors understand disease and make informed decisions on the best treatments for patients,”
Professor Culhane explained.
Professor Gianpiero Cavalleri (School of Pharmacy and Biomolecular Sciences, RCSI) and Professor Denis Shields, (University College Dublin), are Co-Directors of the GDI Ireland project
with Professor Aedín Culhane (University Limerick) and Professor Markus Helfert (Maynooth University and SFI Empower SPOKE Director) as co-applicants.
Prof Culhane’s group will soon be hiring 1 software engineer/postdoc to work on this project. For further information on the project visit: https://gdi.onemilliongenomes.eu.
https://www.ul.ie/news/university-of-limerick-to-support-eu-data-infrastructure-project-tounlock-potential-of
https://www.hrb.ie/news/news-story/article/hrb-supports-genomic-data-infrastructure-gdiin-ireland/
eHealth Hub for Cancer
The All-Island eHealth Hub for Cancer funded by a €4 million grant under the Higher Education Authority HEA Shared Island North-South Research Programme, that combines the strength of the LDCRC and Cancer Research in Queens University Belfast and will study frameworks and international standards for sharing of cancer electronic health data to facilitate tracking of cancer statistics in real-time by harmonising cancer data across the island and linking with global consortia. Sharing data brings enormous benefits to Ireland as it provides the ability to leverage the knowledge of bigger countries, participate in global clinical trials that study new medicines in cancer and work together to develop better national, EU or global policy in disease treatment and prevention.
The eHealthHub for Cancer partners is lead by Prof Aedin Culhane (UL) and Prof Mark Lawler (QUB) and partners with clinical and academic researchers in UCD, RCSI, UG, UCC.
A draft website with more information about the project is online at https://aedin.github.io/eHealthHub/index.html
For more information see: https://www.ilovelimerick.ie/ehealth-hub-for-cancer/ https://www.healthnews.ie/oncology/data-is-a-key-driver-of-successful-outcomes-forpatients/
Prof Culhane’s group will soon be 2 Postdoc (UL) and 5 PhD students to work on this project
UL Research Capacity
We continue to build resources and capacity to perform state of the art cancer research in single cell biology of cancer.
Equipment & resources
Spatial Biology, Digital Pathology & Genomic Sequencing
Akoya PhenoCycler- Fusion - High-plex immunohistochemistry equipment capable of imaging +50 antibodies simultaneously on the same piece of tissue. To enquire about use contact eanna.fennell@ul.ie
Leica Bond RXm Autostainer - Automated immunohistochemistry and in situ hybridisation equipment with customisable protocols. It also provide the capacity to scan slides to facilitate digital image processing. To enquire about use contact eanna.fennell@ul.ie
Illumina NextSeq 1000 Sequencer with high capacity short-read DNA and RNA sequencing
BD Rhapsody Single-Cell Analysis System enable single cell RNA and DNA sequencing
BD FACSMelody Cell Sorter
Research Computing
We continue to work on research computing infrastructure. Prof Culhane and others are worked with UL and VPR office to create a research computing policy for UL and we are also engaging with ICHEC to provide better computational resources.
Cancer Imaging
Sinead O’ Keefe Lab: We are developing in-vivo optical sensors to quantify radiation dose, and provide real-time source localisation, during brachytherapy radiotherapy in prostate and gynaecological cancers. We are also investigating the use of optical fibres for biosensing for cancer diagnosis and treatment.
Bioinformatics and Open-Source Software
Prof Culhane is a member of the Human Cell Atlas project and her group have expertise in analysis of single cell RNA, DNA, proteomics data.
Recent bioinformatics highlights.
Appointment of Maria Doyle as Bioconductor Community Manager, CZI funding
Prof Culhane LERO as part of the open-source software project
Funding
We have attracted considerable research funding. Congratulations everyone.
Upcoming Funding Opportunities
Irish Cancer Society Translational Research Scholarship Programme 2023
The Irish Cancer Society is currently accepting applications for its Translational Research Scholarship Programme 2023. The deadline for applications is 3pm Tuesday 28th March 2023.
The HRI email a monthly newsletter on funding including cancer funding SUBCRIBE or check online
Funding Successes
Ruth Clifford
€100,000 from HRB in 2022, further €60,000 January 2023.
€40,000 from Charitable funds.
Paul Murray
Aisling Ross MSCA Global Fellowship (~€200k)
Eanna Fennell IRC Postdoctoral Fellowship (~€100k)
SFI National Spatial Tissue Profiling Platform (~€1 Million)
Aedin Culhane
HEA Shared Island Strand II award (€4 million of which UL award €1.9 million)
EU/HRB Genomic Data Infrastructure (€200K)
Chan Zuckerberg Initiative €400K
Catríona Dowling
All Ireland Cancer Research Institute (AICRI_Start) grant (€152K)
HRCI-HRB Joint Funding Scheme (€300K)
PUBLICATIONS
1. Lambe G, Doran S, Clifford R, Nasoodi A. Isolated CNS relapse of medullary aggressive high-grade B-cell lymphoma on 18F-FDG-PET/CT. Eur J Hybrid Imaging. 2022 May 3;6(1):9. doi: 10.1186/s41824-022-00130-9. PMID: 35501493; PMCID: PMC9061919.
2. Symth E, Aidan K, David OB, Deirdre W, Sarah B, Emer A, Kanthi P, Crotty GM, Aileen W, Michelle C, Clifford R, O Leary Hilary, Ashique K, Bacon CL, Emily S, McElligott AM, Fiona Q, Elisabeth V, Carmel W. Low CD49d expression in newly diagnosed chronic lymphocytic leukaemia may be associated with high-risk features and reduced treatment-free-intervals. Eur J Haematol. 2022 Nov;109(5):441-446. doi: 10.1111/ejh.13824. Epub 2022 Aug 9. PMID: 35776688; PMCID: PMC9804520.
3. Wang Y, Buck A, Grimaud M, Culhane AC, Kodangattil S, Razimbaud C, Bonal DM, Nguyen QD, Zhu Z, Wei K, O'Donnell ML, Huang Y, Signoretti S, Choueiri TK, Freeman GJ, Zhu Q, Marasco WA. Anti-CAIX BBζ CAR4/8 T cells exhibit superior efficacy in a ccRCC mouse model. Mol Ther Oncolytics. 2021 Dec 31; 24:385-399. doi: 10.1016/j.omto.2021.12.019. PMID: 35118195; PMCID: PMC8792103.
4. Syrimi E, Fennell E, Richter A, Vrljicak P, Stark R, Ott S, Murray PG, Al-Abadi E, Chikermane A, Dawson P, Hackett S, Jyothish D, Kanthimathinathan HK, Monaghan S, Nagakumar P, Scholefield BR, Welch S, Khan N, Faustini S, Davies K, Zelek WM, Kearns P, Taylor GS. The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery. iScience. 2021 Nov 19;24(11):103215. doi: 10.1016/j.isci.2021.103215. Epub 2021 Oct 2. PMID: 34632327; PMCID: PMC8487319.
5. Robbe P, Ridout KE, Vavoulis DV, Dréau H, Kinnersley B, Denny N, Chubb D, Appleby N, Cutts A, Cornish AJ, Lopez-Pascua L, Clifford R, Burns A, Stamatopoulos B, Cabes M, Alsolami R, Antoniou P, Oates M, Cavalieri D; Genomics England Research Consortium; CLL pilot consortium; Gibson J, Prabhu AV, Schwessinger R, Jennings D, James T, Maheswari U, Duran-Ferrer M, Carninci P, Knight SJL, Månsson R, Hughes J, Davies J, Ross M, Bentley D, Strefford JC, Devereux S, Pettitt AR, Hillmen P, Caulfield MJ, Houlston RS, Martín-Subero JI, Schuh A. Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features. Nat Genet. 2022 Nov;54(11):1675-1689. doi: 10.1038/s41588-022-01211-y. Epub 2022 Nov 4. PMID: 36333502; PMCID: PMC9649442.
6. Nohtani M, Vrzalikova K, Ibrahim M, Powell JE, Fennell É, Morgan S, Grundy R, McCarthy K, Dewberry S, Bouchal J, Bouchalova K, Kearns P, Murray PG. Impact of Tumour Epstein-Barr Virus Status on Clinical Outcome in Patients with Classical Hodgkin Lymphoma (cHL): A Review of the Literature and Analysis of a Clinical Trial Cohort of Children with cHL. Cancers (Basel). 2022 Sep 1;14(17):4297. doi: 10.3390/cancers14174297. PMID: 36077832; PMCID: PMC9454639.
7. Nash A, Ryan EJ. The oncogenic gamma herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) hijack retinoic acid-inducible gene I (RIG-I) facilitating both viral and tumour immune evasion. Tumour Virus Res. 2022 Dec; 14:200246. doi: 10.1016/j.tvr.2022.200246. Epub 2022 Aug 20. PMID: 35998812; PMCID: PMC9424536.
8. Khan AO, Reyat JS, Hill H, Bourne JH, Colicchia M, Newby ML, Allen JD, Crispin M, Youd E, Murray PG, Taylor G, Stamataki Z, Richter AG, Cunningham AF, Pugh M, Rayes J. Preferential uptake of SARS-CoV-2 by pericytes potentiates vascular damage and permeability in an organoid model of the microvasculature. Cardiovasc Res. 2022 Dec 9;118(15):3085-3096. doi: 10.1093/cvr/cvac097. PMID: 35709328; PMCID: PMC9214165.
9. Jalali A, Miresse D, Fahey MR, Ni Mhaonaigh N, McGuire A, Bourke E, Kerin MJ, Brown JAL. Peripheral Blood Cell Ratios as Prognostic Indicators in a Neoadjuvant Chemotherapy-Treated Breast Cancer Cohort. Curr Oncol. 2022 Oct 7;29(10):7512-7523. doi: 10.3390/curroncol29100591. PMID: 36290868; PMCID: PMC9600104.
10. Creedican S, Robinson CM, Mnich K, Islam MN, Szegezdi E, Clifford R, Krawczyk J, Patterson JB, FitzGerald SP, Summers M, Richardson C, Martin K, Gorman AM, Samali A. Inhibition of IRE1α RNase activity sensitizes patient-derived acute myeloid leukaemia cells to proteasome inhibitors. J Cell Mol Med. 2022 Aug;26(16):4629-4633. doi: 10.1111/jcmm.17479. Epub 2022 Jul 13. PMID: 35822520; PMCID: PMC9357667.
11. Brown JAL, Bourke E, Hancock WW, Richard DJ. Editorial: Mechanisms guarding the genome. Front Cell Dev Biol. 2022 Aug 15; 10:974545. doi: 10.3389/fcell.2022.974545. PMID: 36046336; PMCID: PMC9421295.
12. Berditchevski F, Fennell E, Murray PG. Calcium-dependent signalling in B-cell lymphomas. Oncogene. 2021 Nov;40(45):6321-6328. doi: 10.1038/s41388-021-02025-8. Epub 2021 Oct 8. PMID: 34625709; PMCID: PMC8585665.
13. Martyn, M, Kam, W, Woulfe, P and O’Keeffe, S. "Water Phantom Characterization of a Novel Optical Fiber Sensor for LDR Brachytherapy." IEEE Sensors Journal (2022).
14. A Giaz, M Galoppo, N Ampilogov, S Cometti, Jennifer Hanly, O Houlihan, W Kam, M Martyn, O Mc Laughlin, R Santoro, G Workman, M Caccia, S O’Keeffe, "ORIGIN, an EU project targeting real-time 3D dose imaging and source localization in brachytherapy: Commissioning and first results of a 16-sensor prototype." Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment (2023): 167999.
15. Cometti, S., Agnieszka Gierej, A. Giaz, S. Lomazzi, Tigran Baghdasaryan, Jürgen Van Erps, Francis Berghmans, R. Santoro, M. Caccia, and S. O’Keeffe. "Characterization of scintillating materials in use for brachytherapy fiber-based dosimeters." Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment 1042 (2022): 167083.