Sunny and chill outside. But PhD students are very busy in the lab with lots to do, record and analyse. Happy with small steps forward. The right size of a PCR band (bottom right), nice looking recombinant bacteria colonies (top right), neuroblastoma cells formed perfect spheroids (multicolour image).
The second review has been published in Journal of Personalized Medicine on March, 16th. Originally, it was a small review project for Nadiya, a medicine student, last summer. However, it became a big one with all data systematically collected, analysed and condensed. The focus of this review was on Retinoic Acid (RA), widely known as Vitamin A and its role in neuroblastoma. RA plays a vital role in human development. The main feature of RA is to push neuroblastoma cells to become neuron-like cell stopping their aggressiveness and cancer fate. So, we wanted to know more about the ongoing research both in the labs and the clinic. We reviewed primary research articles reporting basic and translational findings as well as clinical trials. Hopefully, it would help other researchers to get a full picture of this topic and a structured resource of experimental models and drugs tested.
As the year comes to an end, you are looking back and seeing all achievements in a different light, a light of the COVID glaze. Lab research was at bay for a while, challenges to return and re-start experiments, no scientific meetings in the traditional format where you build your new collaborative net at coffee breaks. Despite all, the team has expanded and we welcomed Ellen and Erin in October.
The NCRC Winter Symposia is a lovely way to wrap the year putting together all hard work and look at the progress done so far. We have an exciting project that has two arms: a blue-sky science and a translational. Working together John and Tom were able to generate promising results on understanding how small membrane-bound vesicles or exosomes can send signals from neuroblastoma cells to cells responsible for new blood vessels formation. They developed a protocol to scale up the production of exosomes, isolate them and characterise. We have a dataset on what these exosomes carry on and now can test how they promote new blood vessels formation. Indeed, more left to do but knowing the direction makes this journey meaningful.
Research is a fascinating journey no doubt. Inquisitive minds try to solve burning puzzles. It takes time. Some puzzles are more complected than the others. One of the hallmarks is the conversion of the resolved puzzle into a scientific story to tell to your peers.
We write and publish these stories. The publishing is another caveat that often makes your story sharper and neater. However, while you are in the process you feel that the mission is impossible.
Delighted to see that one of the missions is completed – a great hallmark for John which coincided with his new research adventure starting in a few days. This is his first first author paper! It is not tautology! It is his first original research paper where he is the first author. This position is a success measure in a research career. His teamwork skills secured him another few original papers. Well done John! Well deserved!
A lot has changed for me since I began my research journey in RCSI, as I transitioned from being an undergraduate placement student to a PhD candidate, however the biggest change has been adjusting to doing a lab-based PhD during a pandemic!
These days my work hours are shared between the labs in RCSI and my family home. While my bench space and office space used to be separated by just a few steps, there is now a 30+ minute bus journey between them. It has certainly put my planning skills to the test as now when I walk into the lab I need to be sure of what I am planning to do, and that I can complete the task in my pre-booked lab time slot.
I appreciate my time in the labs much more now that I spend so much time at home. Whether I am culturing neuroblastoma cells, analyzing proteins or genes by Western blots or PCRs, I enjoy immersing myself in the work knowing that my time on the bench is limited.
The main perk is that now when I am doing computer work – analyzing results, writing reviews, preparing presentations, using online software – I can do it from the comfort of my box-room-office, often very cosy in a blanket as I do it. While my work-from-home desk space is slightly more spacious than my desk in the now-closed “Write-up Room 2”, I do miss the chats and laughs that come with working in a shared office.
One thing’s for sure though, my two dogs very much enjoy the days that I work from home!
Catherine Murphy, Neuroblastoma UK funded PhD student
This summer I worked under Dr Piskareva supervision in the remote research program. My original plans for a lab experience were put down by COVID. My ultimate goal was to write the review article on the potential uses of retinoic acid in neuroblastoma research.
Before starting the project, I didn’t have any specific expectations. While I always had fun picking the primary articles apart and summarising the gathered data during my undergrad and med school, I didn’t believe that this experience would be the special one. And I kept thinking so as I was collecting the information from the numerous data on cell cultures. And as I was looking at the mice models studies. And clinical trials.
Then I started to write my introduction, and so researched the information on the neuroblastoma prognosis, contemporary treatment protocol and outcomes. And suddenly I saw my project in the new light. I was used to regarding the clinical trials outcomes as simple statistics, but this time no desensitization could shield me. Yes, 60% of the patients in the high-risk group die in 5 years after diagnosis, and yes, 90% of those patients are children less than 5 years old. And there is nothing that we could currently do to save those children.
On the other hand, this realisation brought meaning to my work. This time, I was not doing a PubMed search to get a good mark or CV reference. Instead, I was looking for the possible treatment of the disease. My review on the current knowledge about retinoic acid will let the other primary researchers target the most promising drug for future experiments and, eventually, create a novel and effective therapy to help those children.
And isn’t it what we are all striving for in medical research?
Last Friday we said Good Bye to 3 medical students who joined us to gain research experience. It has been quiet in the lab since they finished! It is always interesting to see their evolving journey as researchers.
“This research opportunity has given me the most exciting and rewarding experience during my undergraduate Medicine course. I got hands-on experience in ongoing medical research in Cancer biology which I think is unique of its kind for any undergraduate medical student. Throughout this journey, I could interact with many people coming from different domains including my collogues and my supervisor which giving me the opportunity to form professional relationships. I feel that my medical background helped me a lot along with my passion for the research work what I did in the lab. This research experience gave me an opportunity to gain and strengthen my skills like communication, time management, sincerity and judiciousness. I gained academic skills like scientific writing and critical thinking. I got exposure to various scientific equipment which I think is quite a rare opportunity for any undergraduate medical student. Overall, I think that by committing myself to medical research has given me a chance to understand Medicine from a different angle which I feel is an amazing and accomplishing experience for a medical student like me.” Sanat Rashinkar
“I arrived to the lab on my very first day feeling a little bit nervous but excited at the same time. Firstly, my partner Sanat and I were given a safety introduction talk by Seamus, who seemed very strict in regard to the safety rules but also turned out to be very fun. We then met the team who we’d be working with: Dr Olga, John, Ciara, Catherine, Thomas… Everyone turned out to be very lovely and friendly, making you feel very comfortable in the workplace. I also enjoyed the fact that we’d go for breakfast all together every once in a while; this really makes you feel like a part of a big family. My project was about melanoma and required some training that had to be completed before I could start my actual work. At first, everything seemed quite simple, however, when I started my actual research some things didn’t turn out as nicely as I expected. I mainly struggled with the microscope but Ciara was very patient with me and would give me a hand whenever I struggled. Overall, it was a very pleasant experience that gave me a great perspective into research, working alongside my colleagues on something as important as cancer. I truly believe that anyone who gets a chance to participate in research should really go for it as it makes you look at science differently and can also be fun.” Evgeniia Mustafaeva
Exciting times ahead for my team – to study neuroblastoma – immune cells interaction. This 3 years project is funded by Neuroblastoma UK to support the interdisciplinary collaboration between experts in fields of neuroblastoma biology, immunology and tissue engineering from Royal College of Surgeons in Ireland, Trinity College Dublin and Queen Mary University London.
Catherine will grow different neuroblastoma cells together with immune cells using a 3D printing technology. She will travel to Queen Mary University London and learn how to do 3D tumour bioprinting. This technology allows the generation of reproducible scaffolds that replicate the architecture of tumour tissues as seen in patients. She will use RCSI/AMBER facilities to optimise this model here and to study how immune cells recognise cancer cells, attack and eventually kill them. This experimental model will help us to advance current immunotherapies and develop more effective treatments for neuroblastoma.
I had one of the most enjoyable poster sessions in the last few years! A genuine interest in our 3D in vitro cancer models by both academics and Industry. Hope, to keep the ball rolling and strengthen these new links.
The Symposium programme was an excellent balance of the new transnational outcomes with hardcore developmental cellular programmes. From ‘How neuronal precursors select their fate and how they can escape the developmental constraints? How this knowledge can help to advance our understanding of neuroblastoma aetiology?’ to ‘New drugs that demonstrated great potency in pre-clinical studies’ via ‘how we can work together more efficiently to progress quicker’
Indeed, the success of the research meeting became possible thanks to the strategic vision and leadership of organisers!
Cancer Research UK Cambridge Centre Neuro-oncology Programme Session
Chair: Kate Wheeler (Oxford Children’s Hospital)
13:10 – 13:40 Sandra Ackermann (Cologne): The genetic basis of favourable outcome and fatal tumour progression in neuroblastoma
13:40 – 14:10 Rogier Versteeg (Amsterdam): The dark side of neuroblastoma
14:10 – 14:40 Katleen de Preter (Ghent): Improved diagnosis and risk stratification of paediatric cancers using liquid biopsies
14:40 – 14:55 Sue Burchill (Leeds): Self-renewing neuroblastoma cells isolated from bone marrow aspirates of children with stage M disease share a mesenchymal expression signature: an NCRI CCL CSG Neuroblastoma Group Study
14:55 – 15:15 Combined discussion
15:15 – 15:45 Tea with Posters
Session 2: Targeted & combination therapy I
Cancer Research UK Cambridge Centre Neuro-oncology Programme Session
Chair: Marie Arsenian Henriksson (Karolinska)
15:45 – 16:15 Frank Westermann (Heidelberg): Novel metabolic dependencies of MYCN-driven neuroblastoma
16:15 – 16:45 Gerard Evan (Cambridge): Is Myc really master of the universe?
16:45 – 17:00 Melinda Halasz (University College Dublin): Anti-Cancer Effects of Diphenyleneiodonium Chloride (DPI) In MYCN-Amplified Neuroblastoma
17:00 – 17:15 Evon Poon (ICR, Sutton): Pharmacological blockade of high-risk MYCN driven neuroblastoma using an orally-bioavailable CDK2/9 inhibitor
17:15 – 17:35 Combined discussion
Downing College – Main Hall.jpg
17:35 – 19:15 Poster viewing & Drinks
19:30 Symposium Dinner at Downing College (map for dinner)
FRIDAY 12TH APRIL 08:30 – 08:50 Coffee & pastries
Session 3: Neural crest & differentiation therapy I
Chair: Margareta Wilhelm (Karolinska)
08:50 – 09:20 Igor Adameyko (Karolinska): Normal development of sympathoadrenal system resolved with lineage tracing and single cell transcriptomics
09:20 – 09:50 Quenten Schwarz (Adelaide): Guiding sympathoadrenal neural crest cells to the adrenal primordia
09:50 – 10:05 Claudia Linker (King’s College London): Notch coordinates cell cycle progression and migratory behaviour leading to collective cell migration
10:05 – 10:20 Combined discussion
10:20 – 10:50 Coffee with Posters
Session 4: Neural crest & differentiation therapy II
Chair: Gareth Evans (York)
10:50 – 11:20 Karen Liu (King’s College London): ALK and GSK3 – shared features of neuroblastoma and neural crest
11:20 – 11:35 Anestis Tsakiridis (Sheffield): Efficient generation of trunk neural crest and sympathetic neurons from human pluripotent stem cells via a neuromesodermal progenitor intermediate
11:35 – 12:05 Anna Philpott (Cambridge): Using developmental mechanisms to drive differentiation of neuroblastoma
12:05 – 12:20 Combined discussion
12:20 – 13:20 Lunch with Posters
Session 5: Targeted & combination therapy II
Chair: Bengt Hallberg (Gothenburg)
Cancer Research UK Cambridge Centre Paediatrics Programme Lecture:
13:20 – 13:50 Sharon Diskin (Philadelphia): A multi-omic surfaceome study identifies DLK1 as a candidate oncoprotein and immunotherapeutic target in neuroblastoma
13:50 – 14:05 Donne Nile (Glasgow): Manipulation of cancer cell metabolism for neuroblastoma combination therapy with targeted radiotherapy
14:05 – 14:35 Suzanne Turner (Cambridge): CRISPR-dCas9 screens to identify resistance mechanisms to ALK in neuroblastoma
14:35 – 14:50 Combined discussion
14:50 – 15:20 Tea with Posters
15:20 – 15:30 Poster prizes
Session 6: Targeted & combination therapy III
Chair: John Lunec (Newcastle)
15:30 – 16:00 Per Kogner (Karolinska): The PPM1D encoded WIP1 phosphatase is an oncogene significant for cancer development and tumour progression and a druggable therapy target in neuroblastoma and medulloblastoma. A hint as to how aggressive childhood cancer manages with wild-type p53
16:00 – 16:15 Deb Tweddle (Newcastle): Preclinical assessment of MDM2/p53, ALK and MEK inhibitor combinations in neuroblastoma
16:15 – 16:30 Sally George (ICR, Sutton): A CRISPR-Cas9 genomic editing and compound screening approach identifies therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma
16:30 – 16:45 Miriam Rosenberg (Jerusalem): Expression- and immune-profiling of neuroblastoma-associated Opsoclonus Myoclonus Ataxia Syndrome (OMAS) to identify features of auto- and tumour-immunity