Pathological blood vessel formation (angiogenesis), or the inability of endothelial cells to perform their physiological function (endothelial dysfunction), are defining features of disease. The endothelium actively controls vessel integrity, vascular growth and remodelling, tissue growth and metabolism, immune responses, cell adhesion, angiogenesis, haemostasis and vascular permeability. It is, therefore, a vital and largely unexploited target for novel therapies.
Prof Tracy Robson’s team have identified and characterised a novel anti-angiogenic protein, FK506 binding protein like – FKBPL, significantly advancing our understanding of the anti-angiogenic process, in particular, how tumours recruit blood vessels to support their growth. This led to a collaborative study with Almac Discovery to develop therapeutic peptides based on FKBPL’s active domain to explore their potential in cancer by targeting the ability of tumours to recruit blood vessels to grow, invade and metastasise beyond the site of the primary tumour. The team are also testing the ability of these peptides to sensitise tumours to current therapies and to target cancer stem cells that lead to the onset of resistance and/or recurrent disease. Importantly, these studies led to a ‘first in man’ phase I clinical in cancer patients where the clinical candidate drug, ALM201, was very well tolerated over a wide range of doses. Prof Robson’s team (Dr Stephanie Annett and Dr Gillian Moore) will discuss this data together with new data suggesting a strong role for FKBPL in vascular endothelial dysfunction and possible implications therefore in other diseases associated with vascular disease.
Please join me in offering congratulations to ‘Drs’ Shane O’Grady and Brian Mooney who successfully defended their PhD thesis yesterday:
Shane’s: Investigation of the functional roles of calcium channels, inflammatory cytokines and tumour micro-environmental factors in a human in vitro model of breast cancer calcification
Supervisor: Maria Morgan
Brian’s: The role of the anorectic neuropeptide CART in breast cancer. Supervisor: Darran O’Connor
I wanted to congratulate everyone for their significant contributions to recent RCSI Research Day. MCT’s presence was strong on the day with a number of keys oral and poster presentations from across the four MCT research pillars.
In particular, a huge congratulations to:
Dr Joan Ni Gabhann for the Most Highly Cited RCSI Senior Authored Paper with Industry Collaboration 2012-2016 for her paper ‘Btk regulates macrophage polarization in response to lipopolysaccharide’.
Rebecca Watkin (PI Prof Steven Kerrigan) and Edmund Gilbert (PI Prof Gianpiero Cavalleri) who jointly won the best postgraduate oral presentation, sponsored by Bio-Sciences Limited, for their presentations on ‘S.aureus induced miR330-3p expression triggers abnormal permeability in an ex-vivo 2D model of sepsis’ and ‘The Irish DNA Atlas: Revealing Fine-Scale Population Structure and History within Ireland’, respectively.
Prof James O’Donnell (ICVB) who won the Clinician CEO Innovation Award.
Dr Ingmar Schoen for his novel Invention Disclosure.
Camille Hurley (PI Dr Darran O’Connor), Edmund Gilbert (PI Prof Gianpiero Cavalleri) and Conor Duffy (PI Claire McCoy)for winning inaugural RCSI International Secondment Awards.
Finally, well done to Dr Claire McCoy for giving an inspiring and heartfelt presentation about her SFI President of Ireland Future Research Leader Award.
On November 14th, we welcomed almost 50 secondary school students at our Department for Lab Safari. The event was designed to encourage young people to consider a career in Science, Technology, Engineering, Maths and Medicine through hands-on experience and demonstrations prepared by our researchers. We developed 6 different workstations focused on Cancer biology and biomarkers, Drug Discovery, Multiple Sclerosis, Human Genetics and Immunology/Body clock
The event was opened by Prof. Tracy Robson, Head of MCT, sharing her career path in research and lessons that she learnt. Dr Avril Hutch, Head of RSCI Equality and Diversity Unit, also spoke about stereotypes in STEMM careers and having an awareness of unconscious bias.
Our workstation was led by Caragh Stapleton, Katherine Benson and Edmund Gilbert, centered around human genetics. Our activity set out to teach participants about inherited traits and demonstrate how variation in our DNA influences our physical attributes. We investigated a number of traits including PTC taster (using PTC taste strips), colour blindness, widows peak, tongue rolling, attached earlobes, bent little finger, eye colour and red hair. Each participant noted whether or not they had the given trait and we then discussed the hypotheses of the genetic variants influencing the different traits.
Our workstation was led by Olga Piskareva and John Nolan. We explained the concept of biomarkers and the importance of discovering novel biomarkers for neuroblastoma, a childhood malignancy. Various chromosomal aberrations can be biomarkers of neuroblastoma aggressiveness. One of the strongest predictors of rapid neuroblastoma progression is MYCN status. We selected several neuroblastoma cell lines with known MYCN status providing a good illustration of biomarker’s quantity. Using immunodetection, we visualised the differences in the MYCN presence.
Our workstation was led by Annie Curtis, Mariana Patricia Cervantes Silva, George Timmons and Cathy Wyse. The theme of our activity was on the body clock and immune function. We discussed with the students why they get jet lag and what that has to do with their body clock. Students then moved to the first station where they got a chance to add colouring to macrophages, so we had red, yellow, blue and green macrophages and were able to look at their coloured macrophages under a microscope. Then they moved to the next station where they got to see the master clock which resides in the hypothalamus of the brain under a microscope. Finally, we displayed some images of activated macrophages and explained their function.
Cancer Cell Biology
Our workstation lead by Sudipto Das, Gillian Moore and Stephanie Annett, focused on showcasing the various laboratory-based approaches applied regularly to identify and investigate novel gene or protein-based biomarkers of cancer progression. Within our workstation, we highlighted three key areas including how samples following biopsy from a cancer patient are used to construct tissue microarrays which are used for assessing the importance of a certain protein in cancer. This was followed by demonstrating a particular tissue culture-based method used to study anti-cancer properties of drugs and finally displaying an array of microscopic images of blood vessels developing in a given tumour.
Our workstation was led by Claire McCoy, Remsha Afzal and Conor Duffy. The research focus at our lab safari station was Multiple Sclerosis (MS). We explained how the causes of MS are unknown, but that it is characterised by an influx of immune cells into the brain and spinal cord. Our research aims to investigate one type of immune cell called the macrophage. We aim to understand the damage macrophages cause in MS and if we can reverse this to provide an alternative tool for MS therapeutics. We really enjoyed explaining our research at the Lab Safari, where we showed students how MS impacts on brain function and showed them examples of activated macrophages under the microscope.
Our workstation was led by Dermot Cox and Padraig Norton. Students were given a brief history of drug discovery. Then they were introduced to the basic concepts of how a drug binds to its target and the different ways in which a drug can bind. Students were then shown a demonstration of molecular docking on a computer whereby a small molecule, or drug candidate, was virtually docked into a target binding site using the software.
The event was led by Dr Maria Morgan, Anne Grady, Prof. Tracy Robson, Dr Olga Piskareva and John O’Brien. Guides on the evening included Olwen Foley, Camille Hurley, Mary Ledwith, Seamus McDonald and Shane O’Grady.
Please join me in sending congratulations to the following staff: Sudipto Das and Jennifer Dowling on their appointment as Honorary Lecturer[s] within MCT, recently approved by Academic Council.
Sudipto Das on the award of best poster presentation in the Post-doctoral researcher category for poster titled “Using next-genera-on sequencing strategies to guide precision oncology in cases with atypical clinical presentation” at the Irish Society for Human Genetics Annual Conference held at Croke Park, Dublin on 15th Sep, 2017.
Jamie Early, student with Annie Curtis, for the best short talk at the Irish Society for Immunology Annual meeting. The title of talk: The circadian clock protein BMAL1 regulates inflammation in macrophages via the NRF2 antioxidant defense pathway”.
And finally to ‘Dr’ Rana Bakhidar PhD, who successfully defended her thesis last week. The title of her thesis is ‘Nanoparticles Used in Drug Delivery and Targeting: Understanding the relationships between Nanoparticle Quality And Interaction With Platelets’. Supervisor: Dr. Sarah O’Neill and Co-supervisor, Dr Zeibun Ramtoola, School of Pharmacy,
Well done to all!
Professor & Head of Molecular & Cellular Therapeutics (MCT)
Over the last 10 years, Prof Tracy Robson has collaborated closely with Almac Discovery on the development of the therapeutic peptide, ALM201, based on her initial research into the anti-angiogenic properties of FKBPL. ALM201 is part of the active anti-angiogenic domain of FKBPL and is a potent inhibitor of angiogenesis both in vitro and in vivo. The technology was patented by Professor Robson and licensed to Almac Discovery. Following collaborative pre-clinical work showing robust efficacy, this ‘first-in-class’ FKBPL-based antiangiogenic peptide has entered phase I/II clinical trials in the ovarian setting (EudraCT No: 2014-001175-31). Whilst the trial is ongoing, we have received exciting news that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to the drug candidate ALM201 in the treatment of ovarian cancer. The FDA Office grants orphan drug designation to encourage the development of drugs for the prevention, or treatment of a medical condition affecting fewer than 200,000 people in the US and grants market exclusivity for a seven-year period if the sponsor complies with certain FDA specifications. Receiving Orphan Drug Designation for ovarian cancer underlines the fact that ALM201 may address a significant unmet medical need for this important disease.
Prof Tracy Robson (MCT), Prof Jochen Prehn (Physiology & Medical Physics) and Dr Darran O’Connor (MCT) have recently returned from 1 week at the College of Pharmaceutical Sciences, Soochow University, Suzhou, China where they participated in a workshop with faculty to explore research collaborations and future joint funding applications under the newly announced SFI-NSF Partnerships for International Research and Education. Supported by an Erasmus+ programme coordinated by Prof Marc Devocelle (Department of Pharmaceutical and Medicinal Chemistry), the workshop involved presentations from RCSI and Soochow investigators describing their work and discussion to identify areas of synergy. Afternoon lectures by RCSI faculty were opened to postgraduate and postdoctoral researchers from Soochow, leading to a vigorous and stimulating discussion and Prof Xinliang Mao from Soochow will visit RCSI next month to further strengthen future collaborative research opportunities.
At the invitation of the President of the British Pharmacological Society, Professor John Waddington (Emeritus, RCSI) has been elected to Fellowship of the Society; this is in recognition of his career contributions to research, education and service in the discipline of pharmacology, not just in Ireland but globally. He has recently returned from 3 weeks at the College of Pharmaceutical Sciences, Soochow University, China, under his joint appointment as a Professor of Pharmacology. While there, he continued collaborative research, gave undergraduate lectures and fostered further joint endeavours between RCSI and Soochow University, which is in the top 5% of Chinese research universities.
MCT was well represented in the award ceremony at the recent Research Day; our congratulations go to the following:
Dr Mark McCormack, for receiving prizes in the RCSI Author Citations Prizes in two categories – the 2011 Most Highly Cited RCSI Senior Authored Paper and the 2011-2015 Most Highly Cited RCSI Senior Authored Paper with International Collaboration – for his paper entitled “HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans” published in the New England Journal of Medicine.
Dr Cathy Wyse, as part of Dr Annie Curtis’s group, was presented a prize for the front cover illustration of the RCSI Research Day abstract book, for a striking image of glial cells at the junction between the brain and pituitary gland.
Tony McHale, PhD student at the School of Pharmacy, & MCT, and the Irish Centre for Vascular Biology, RCSI received the prize for the best postgraduate oral presentation, for his talk on the topic of “First in Class Potential Novel Drug for the Treatment of Sepsis Caused by Urinary Tract Infections”.
Medical student Jack Donohue [RSS student], was awarded the Dr Harry O’Flanagan Prize for Excellence in Undergraduate Research for the best undergraduate oral presentation for a project carried out as part of the RCSI Research Summer School entitled “Sanger Confirmation of Suspected Epilepsy-Related Pathogenic Variants Identified Through Next-Generation Sequencing”.
Many thanks to all members of MCT; without you, our success would not be possible. Wishing you and your family all the warmth this Holiday Season has to offer. Have a wonderful Christmas and a New Year filled with peace, joy and success.
It gives me great pleasure to welcome you to MCT’s blog page. Our department is based within the Royal College of Surgeon’s in Ireland (RCSI) situated on Dublin’s beautiful St Stephen’s Green. This was one of the initial attractions for my move to Dublin from Queen’s University Belfast in Aug 2016, in addition to the vibrant and innovative environment that RCSI provides, through its achievements in education and research.
Our research focuses on understanding the molecular basis of disease in order to develop and apply our findings to the identification of biomarkers and new drug targets. Our aim is to improve the diagnosis, treatment and, ultimately, prevention of disease; enabling MCT to be at the forefront of personalized medicine. With newly renovated state-of-the-art facilities, strong links with Beaumont Hospital, our clinician-scientist teams are leading therapeutic and biomarker discovery in the areas of autoimmune and inflammatory disease, cancer, cardiovascular disease, infection, platelet biology and neurological and psychiatric disease. This is facilitated by strong collaboration with industry allowing us to translate our findings appropriately, revolutionizing healthcare through discoveries and innovations that improve people’s lives.
I hope that you enjoy reading our blog page which seeks to capture the dynamic nature of the teaching and research environment within MCT and pays testimony to the significant accomplishments of our all of our staff and students. I hope that we can inspire you ………