Sparkles of A Researcher Day

Once I mentioned the importance of the publication track record for a career in science. My team has been productive despite the COVID pandemic. Two review articles were published.

The first was a review written by Tom and published in Cancers focusing on the small extracellular vesicles produced by cancer cells that can transfer various growth signals to the tumour microenvironment aka neighbourhood and promote tumour expansion. The signal in focus was a protein called epidermal growth factor receptor (EGFR). It contributes to the healthy fitness of many different cells in the body. However, many cancer cells produce an excess of this protein giving them an advantage of growth over normal cells. Increased EGFR can be seen in breast, lung, glioblastoma and head and neck cancers.

Cancers 202012(11), 3200; https://doi.org/10.3390/cancers12113200

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.

J. Pers. Med. 202111(3), 211; https://doi.org/10.3390/jpm11030211

International Childhood Cancer Awareness Day 2021

Every year, we celebrate Childhood Cancer Awareness Day Internationally. Pre-COVID times, it was straightforward to do a coffee morning, a bake sale, or as we did a Hot Chocholate morning.

To be honest with you, I had almost no presence of childhood cancer in my life until I joined Prof Stallings lab in 2011. When I said ‘almost’, I meant during my adulthood.

My Dad had a younger brother, both started their families at the same time. Our families used to spend a good time together, holidays, birthdays and weekends together. Both I and my cousin Igor were born almost within a year. I remember our play days together but at the level of feelings and stories told by my parents. In the pic, we were held by my nanna.

I do not have a pic where we were 3- or 4-years old. No pic was taken after Igor was diagnosed with blood cancer. He was 1-1.5-year-old. He travelled 800km to the best paediatric oncologists to receive the most progressive treatment back then. It extended his time with the family by four years. But he lost his battle…

How much can remember a 1-, 2-, 4- years old? My last memory – Igor was sleeping in a neat coffin. Adults were muttering. I remember, a tear slowly rolled down from Igor’s closed eyes. I naively asked my nanny why did the dead cousin cry??? He did not want to leave us, – said my nanny softly. 

Back then parents were not much informed on the disease, treatments, odds and alternative options. Igor was suffering, no pain relief options were available… No palliative care… Remember my nanny’s words: “These doctors had no hearts. All this child needed was a sense of peace, quiet time with his parents away from the hospital wards”. 

Many things have changed since then. Eight out of 10 children with blood cancer are responding to treatment well, they reach adulthood, may even have kids of their own. However, there are some types of childhood cancers that do not respond well and can return to being more aggressive. Cancer steals the child’s future. One of the thieves is neuroblastoma, a solid tumour of undeveloped nerves.

Childhood cancer research is essential to return happy days to kids and their families. Many childhood cancer research charities do their best to secure funds and support researchers like me. It is vital to have a continuous investment in research that helps to understand the weakness of childhood cancer and develop new drugs designed exclusively for kids.

Today I want to thank 3 charities for their hard work: Children’s Health Foundation Crumlin, Neuroblastoma UK and the Conor Foley Neuroblastoma Cancer Research Foundation. And ask you, my readers, to donate to a childhood cancer charity of your choice.

How neuroblastoma cells spread?

Since I joined neuroblastoma research, I have been puzzled by the fact that half of the children with neuroblastoma have the disease spread at the time of diagnosis. It is still a puzzle whether cells spread and primary tumour growth happen simultaneously or more adventurous cancer cells escape the primary tumour location later.

At a cancer conference, I met Prof Ewald who studies this process in breast cancer. I was fascinated by the approach and started to look for opportunities to join his lab. To tell the truth, very few exist for mid-stage career scientists! One of them is the Fulbright program.

One day, I opened my email saying that I received a Fulbright-HRB Health Impact Scholar Award to travel to Johns Hopkins University and adapt their 3D models to learn how neuroblastoma spreads. It was a life-changing experience both personally and professionally. The amount of experimental data collected over 4 months of work did not fit a 1TB memory stick! Indeed, this short journey was just a start of a new research inquiry.

On my return home, the greatest task that remained was to make sense of every single experiment. Cian Gavin took over and spent almost a year systematising, characterising it, and placing it into a context. It was meticulous work with very little known about invasion strategies in neuroblastoma. Now, we are happy to share our findings published on Cancers.

Where do we go now? Well, our next step is to understand the cellular players behind neuroblastoma invasion and how we can target them to stop neuroblastoma spread. It won’t be a short and sweet journey, but we are ready for it!

This fantastic and rewarding work was supported by Fulbright Commission Ireland, National Children’s Research Centre, Health Research Board, Science Foundation Ireland, the National Institutes of Health/National Cancer Institute (Prof Ewald), Alex’s Lemonade Stand Foundation for the COG Childhood Cancer Repository (Prof Reynolds) and the National Institutes of Health/National Cancer Institute (Prof Reynolds).

Annual NCRC Symposia 2020

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.

Hallmarks of Research

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!

This study is an excellent example of the many roles that small RNA molecules such as miR-124-3p can play in neuroblastoma pathogenesis. The ability of this miRNA to work together with standard chemo drugs can be exploited further in the development of new anticancer therapeutics targeting relapse and drug-resistant tumours.

10 Laps 10km: We raised a grand total of €1419

Last month we set ourselves the “10 Laps 10km” challenge for Childhood Cancer Awareness.

Now we have closed the GoFundMe and counted the charity buckets. We are delighted to announce we raised a grand total of €1419! We are over the moon with this sum, as 2020 required a very different kind of fundraiser than previous years. 

Our three chosen charities: Children’s Health Foundation Crumlin (formerly CMRF), the Conor Foley Neuroblastoma Cancer Research Foundation, and Neuroblastoma UK, will each receive just over €470. 

We’d like to say big thank you to everyone who donated. It will make a huge difference for these charities, this year especially, paving the way to better treatment options for children with cancer in the future.

10K Vhi Women’s Mini-Marathon – #POWEROF10

The new norm, new challenges, new excitement and new achievements! We all proud to say that we completed 10K Vhi Womens Mini marathon socially distanced. Our paces were so different that distancing came absolutely natural. We ran it individually but were a team mentally. Even the capricious Irish weather was our ally. The Sun was bright. The air was fresh and crispy.

This was an individual challenge #POWEROF10: just you and the trail. 10 laps around St Stephen’s Green park were to make the target 10K in aid of Childhood Cancer Awareness Month. The celebration of life, therapeutical advancements, the strength of little patients battling their cancer and their families, doctors and carers who are supporting them in their journey. The emphasis on the gaps in available treatments and diagnosis and the importance of research that needs funding.

Personally, my 10K were split into two parts. The first 4K were full of arguments with my body. Why didn’t I like to do laps? Could I complete 10K? Was I fit to do it? Keep going! No walking – better slow jogging. Did one lap make 1K? Should I do a longer lap instead? And so on and so forth. Then, the second part kicked in. My body stopped arguing and began to enjoy it. I noticed beautiful Autumn colours on the trees, people walking around with a cup of coffee or chatting away, saw my team members overtaking me, and our volunteers counting our laps. People on the street and in the park were cheering us up. What a wonderful and fulfilling day!

As Catherine says: “The 10 Laps 10km challenge was tough! Like many people, I took up running casually during the lockdown, however, I never did more than a couple of kilometres at once, so I was absolutely not prepared for running 10. But the cheers from our socially distanced spectators and all the online support we received meant I got through it. Also knowing what a positive impact this challenge could have for the future of childhood cancer treatment provided plenty of motivation to finish the race 💛🎗”

10K by 6 team members socially distanced. #POWEROF10. Go Gold! Let’s reach 1.5k in donations!

Our Go Fund Me page is still open until this Sunday (October 11th midnight) if you wish to support us.

One Day of the Life as a Researcher: PhD student

Our team is expanding – we are welcome our new PhD student Ellen King! Her project will add another dimension to neuroblastoma research. She will look into potential targets on the surface of neuroblastoma cells resistant to therapy and investigate how we can strengthen the patient immune system response.

Like everyone, my current workspace looks very different from what it normally looks like. I have just joined the Cancer Bioengineering Group as a PhD student in the midst of the pandemic. Certain moments like induction day or meeting my new lab mates, will all be done virtually due to the pandemic. Luckily, I have spent the last year working as a research assistant at RCSI and this has taken away all the stresses of finding my way around a new campus and indeed making friends. Without a doubt, the transition is and will be a strange one but the excitement and enthusiasm haven’t gone anywhere! 

Recently, my days as a researcher have been spent at my lovely, newly-built (with the help of IKEA instructions) home desk. And as the picture I have standing proudly beside my laptop says, there really is no place like home. I feel very lucky to be able to safely work from home and continue my research while so many people are now without jobs or are risking their lives to keep people safe during the pandemic.

NÍL AON TINTEÁN MAR DO THINTEÁN FÉIN” – THERE IS NO FIRESIDE LIKE YOUR OWN

Most days I wake up early and go for a run along the lovely canal beside my house. This is a great way to wake up my brain and is also great preparation for our virtual VHI mini-marathon on the 7th of October 2020 in honour of Childhood Cancer Awareness Month. I start work at around 9am, which at the moment is mostly research, reading papers and writing a literature review in preparation for my return to the lab soon. I miss the experimental side of my research and am really excited to start this new exciting project. 

Ellen King, PhD student

One Day of the Life as a Researcher: undergraduate student

This summer, I had an amazing opportunity to work under the supervision of Dr. Olga Piskareva. I scheduled to join the lab for the second time, however, this plan was unfortunately cancelled to the COVID19.  I was still hopeful and later I got the opportunity to work on a remote research project. My goal was to write a comprehensive review of existing and prospective antigens for antibody specific immunotherapy for neuroblastoma.

This was my first literature review and I was excited about it. I had previously worked on a lab neuroblastoma project that’s why I was familiar with the topic. However, this was a completely new and different undertaking for me.  Before starting the project I had to understand about literature reviews are and how are they written. My project involved looking at a lots of clinical trials and PubMed articles. I had to learn about how clinical trials work and had to develop a search strategy for the project. I understood that literature reviews are a very important part of lab research and forms its backbone. 

Sanat’s review focussed on antibody-based immunotherapy in neuroblastoma, which aims to induce ‘antibody-dependent cellular cytotoxicity’ to kill cancer cells. Luckily, Sanat had wet lab research experience in 2019 pre-COVID where he got to present a research project at the Matrix Biology Ireland meeting.

I started writing the project and ended up writing 40 pages! I developed awesome illustrations to support my review using the software. This was one of the most enjoyable parts of the remote research! As I was writing the project I understood that ‘Neuroblastoma is a devasting disease for children and the tremendous amount of effort and knowledge is being built upon to find a better and enhanced treatment to reduce the disease burden.’ 

I learnt and gained many critical skills during this review. My review on the existing and prospective knowledge about immunotherapies will enable researchers to get a summary of knowledge that will aid in giving them direction to eventually, create effective immunotherapy to defeat neuroblastoma. 

Sanat Rashinkar, 3rd Year RCSI Undergraduate Medicine Student