The RCSI Cancer Bioengineering Group hosted an in-person event during the National PPI Festival 2024 to share their childhood cancer research and connect with the public and patients.
We welcomed members of the public, family members of children with cancer, researchers, clinicians, and patient/community organisations on October 17th. Our past lab members and students paid a visit, too! Our group shared ongoing research on neuroblastoma biology and finding new treatments. Prof Cormac Owens from CHI brought us through the journey of clinical trials in neuroblastoma patients. We heard the heartbreaking story of the brave young man who lost his life to neuroblastoma and his parents who never gave up. This truly inspirational family founded a charity – the Conor Foley Neuroblastoma Cancer Research Foundation, to support curiosity-driven and translationally-focused research. The Foleys know very well how important it is to return happy days to kids and their families.
HDAC inhibitors are drugs that target specific enzymes involved in gene regulation. This study tested broad-spectrum HDAC inhibitors as standalone treatments and combined them with doxorubicin, a well-known chemotherapy drug.
But why on Zebrafish? The zebrafish model provides a rapid and efficient means of testing these treatments, offering valuable insights into their potential use in combating neuroblastoma. This model allows for assessing drug efficacy and helps understand the associated toxicities quickly, making it a powerful tool for developing new anti-cancer therapies.
In the study, fish larvae were implanted with fluorescently labelled, well-established neuroblastoma cell line (SK-N-BE(2)-C) and patient samples (HD-N33, NB-S-124) to grow tumours. Non-cancerous cells (VH7 fibroblasts) were utilized to verify that tumour progression in zebrafish was specific to tumour cells. The engraftment of human cells into fish larvae was confirmed by immunohistochemistry (IHC) staining on zebrafish sections injected with neuroblastoma cells (SK-N-BE). This was achieved using a STEM121 antibody that reacts specifically with a human cytoplasmic protein. The findings showed that pediatric tumour cells survive and grow in the zebrafish model at rates like those observed in human tumours.
Before testing drug efficacy in zebrafish xenografts, optimal drug concentrations and maximal tolerated doses (MTD) were determined. Toxicity tests were conducted by treating fish larvae cells for three days without tumour cell injection to identify the maximum tolerated dose that did not cause observable morbidity, changes in morphology, or severe aberrations in larval behaviour. and lethal dose (LD) for each compound. To find optimal drug concentrations, larvae with xenografted tumour cells were incubated with increasing drug doses 24 hours post-implantation to the maximally tolerated dose (MTD). The relative IC50 values were then determined based on changes in tumour mass volume.
To evaluate the treatment, SK-N-BE(2)- cells were used to test the broad-spectrum HDAC inhibitors, including panobinostat, vorinostat, and tubastatin A, both alone and combined with doxorubicin. The partial response rate (PR) was measured to see how well different drug combinations work to shrink tumours in the zebrafish model. Here’s what they found: Doxorubicin combined with panobinostat resulted in a 23% PR, Doxorubicin combined with tubastatin A showed a 31% PR, and Doxorubicin combined with vorinostat achieved the best result with a 36% PR.
To test the effectiveness of the HDAC inhibitor treatment, they monitored the tumour growth using a confocal microscope before and 48 hours after giving the drug. The test revealed that a 48-hour treatment of SK-N-BE (2)-C zebrafish xenografts with vorinostat and doxorubicin alone, `and in combination, increased cell death. The combination of these two drugs was the most effective, causing a significant increase in cancer cell death (apoptosis) by decreasing cell proliferation, as indicated by reduced PPH3 marker and activating the number of Cleaved caspase-3 (Figure 1).
Figure 1: Treatment for 48 h with Vorinostat, doxorubicin, or a combination of both increased the amount of cleaved caspase-3 and reduced mitotic tumour cells. Adapted from Pharmaceuticals2020, 13(11), 345
In essence, this study validates the use of HDAC inhibitors in treating neuroblastoma and paves the way for broader applications of zebrafish models in cancer research. As we look to the future, these innovative models could significantly enhance our ability to develop effective cancer therapies, making strides towards better treatments and, ultimately, more effective cures.
This article by Krieger et al. discusses the most common form of brain cancer called glioblastoma. Due to its highly aggressive nature, research must be conducted consistently and rapidly to develop new treatments. This has proven challenging due to primary tumours being resected before further research can be done, as well as the lack of current technologies to fully explore relationships between GBM and surrounding brain tissues. This study aimed to study the aforementioned interactions in under 4 weeks, accounting for the rapid progression of the disease in real life.
GBM cells were first derived from four patients and treated with glutamine, heparin, epidermal and fibroblast growth factors, then underwent a sequence of manipulations, such as second-generation replication lentivirus infection of GBM cells, iPSC line 409b2 inoculation in Aggrewell plates and later manipulation with invasion assays, and scRNA sequencing, which, along with the Aggrewell cells, produced neural progenitor cell spheroids for analysis. Confocal microscopy and the developed image processing algorithm allowed for visualization of these cells following fluoroscopy and depicted consistent growth of tumour cells. There was also the growth of microtubules. Any dissociated organoids were then co-cultured with GBM cells again, promoting interaction between the two. Further analysis revealed the upregulation of 45 genes, including PAX6, GJA1, GPC3, and others involved in cell regulation.
In conclusion, this novel mechanism of analysis of GBM cells using Aggrewell plates provided fruitful results, indicating intricate relationships between GBM cells and organoids, providing crucial insight for treatments by elucidating specific gene expression, heterogeneity of cells, and offering new targets based on ligand-receptor interactions. The particular relevance of this study to my work is regarding the usage of Aggrewell plates, which I am currently studying to determine how best to keep cells growing successfully within the wells. This article proves the usability and efficiency of Aggrewell and establishes its crucial role in the realm of brain cancer treatment research.
Massive congratulations on the official moulding of PhD and MSc by Research to our promising young scientists: Rabia Saleem, Dr Ciara Gallagher and Dr Ellen King! Great accomplishments!
Three different journeys, with two through the COVID-19 pandemic. The full range of ups and downs. Who said that the PhD is a straight line? It has never been. It is more like the Irish weather: some days are sunny and bright, and some have scattered showers, gale winds and stormy snow, with sunshine developing elsewhere. The journey was spiced up with publications, conferences, travels, days out and fundraising events with the team.
It is a proud moment for me as well. 🙂 Three PhD and one MSc by Research students graduated within the last 12 months.
Of note, Ellen was behind our Twitter activities in the past, making our team visible!
Wish you all the best of luck on your new adventure!
Every September, we celebrate Childhood Cancer Awareness Month. This is a great opportunity to raise awareness about childhood cancer. Unfortunately, kids get cancer, too. While much research has been done to understand how cancer develops in adults, we still know very little about what exactly leads to cancer in children.
We are the Cancer BioEngineering Group led by Dr Olga Piskareva at the RCSI University of Medicine and Health Sciences. Our research focuses on neuroblastoma, an aggressive childhood cancer of immature nerves. The group has 7 PhD students developing research projects around neuroblastoma biology. One postgraduate student successfully defended her work and was awarded a PhD last month.
We are a dynamic group proud to be engaged in research, science communication and patient involvement. We do that through different initiatives. Throughout September, we will share many of them and invite you to keep following us on social media.
Team 2023
Our projects address topics related to neuroblastoma microenvironment, cell interactions, tumour resistance and the development of new therapies. To do that, we use 3D in vitro models, identify immunotherapeutic targets and evaluate extracellular vesicles.
We are always happy to answer questions and interact with the public. Follow us on our social media channels and read our blog to learn more about us and our research.
We are running a fundraising event, “A knit-a-thon,” on the 19th of September. Stay tuned!
Thanks for reading, and we go ahead with neuroblastoma research!
This blog takes you to the exciting scene of my MSc graduation ceremony at the University of Siena, Italy, completed with the prestigious laurel wreath.
I graduated during COVID-19, but there was no graduation ceremony at that time. Years later, I was invited to attend an “Alumni conference” by the University of Siena, but the plan was still unclear. When we arrived in Siena, we came across that there was a convocation ceremony tomorrow. Hold on! What? Yes, after years of waiting, it was finally taking place on June 7, 2023.
The next morning, all the former students from 48 countries came together in the University’s Grand Piazza del Duomo, where all of the Professors and sponsors, robed in their academic attire, delivered speeches that inspired and reminded us of the responsibility that comes with education, which ended in the most captivating moment of adorning us with laurel wreaths stating that “Rating your thesis attributes by authority granted to me by director I confer you the Masters Diploma in Vaccinology and Drug Development, Congratulations!”. The weight of this academic success was alleviated by our family members’ joyful yells and applause.
Walking out of the ceremony, wreathed in laurel, walking through Siena’s streets with classmates I’ve never met in person, hearing these words “Complimenti! Felicitazioni!” from commoners, I came back to Dublin with an ethereal sensation of pride and belonging that will remain with me for life. Altogether, It was a once-in-a-lifetime experience for me.
Here are some glimpses of the ceremony:
P.S.: But this was not the end. I embarked on a wet-lab MSc in RCSI Dublin. As I am typing these lines, my MSc by Research work has just been submitted for examination, marking another hallmark and opening a new chapter in my life, “the PhD journey”.The new chapter – the new challenges and opportunities!
Eight weeks ago, my journey into the intricate world of neuroblastoma began as I embarked on a remarkable research experience with the Cancer Bioengineering Group at RCSI. Guided by Dr. Olga Piskareva and supported by RCSI Research Summer School, this experience would transform my perspective on scientific exploration forever.
On my first day in the lab, excitement and nervousness mingled within me. But as I stepped into the bustling lab space, I was greeted with warm smiles and a sense of camaraderie among the researchers. The Cancer Bioengineering Group was known for its collaborative spirit, and it didn’t take long for me to feel like a valued member of the team.
RSS 2023 in Action
The research work was a perfect blend of diversity and fascination, encompassing both desk assignments and hands-on lab experiments. The highlight of it all was the chance to work with the cutting-edge 3D bio-printing machine, Rastrum. Witnessing the process of 3D bio-printing and using it to seed the Kelly cell line in various matrices left me in awe of the potential this technology held for future cancer therapies.
Yet, this journey extended beyond the realm of research. It was about the people – the passionate researchers who inspired and supported one another, the dedicated support staff who kept the lab running smoothly, and most notably, Dr. Olga Piskareva and Alysia Scott. They were more than mentors; they became friends and confidants, guiding me through challenges with unwavering support and celebrating our achievements as a team.
As the eight weeks drew to a close, I couldn’t help but reflect on the immense growth I had experienced professionally and personally. The cancer bioengineering field has unveiled the possibilities of using engineering principles to combat a disease that has touched countless lives worldwide.
This journey instilled in me a profound sense of purpose – a drive to contribute to the fight against neuroblastoma and other devastating illnesses. With a heart full of gratitude, I bid farewell to the Cancer Bioengineering Group at RCSI, knowing that the friendships forged and the knowledge gained would forever shape my future endeavours in the world of cancer research.
In the end, it wasn’t merely an eight-week stint; it was a transformational odyssey that solidified my passion for scientific discovery and my determination to make a difference in the lives of those affected by cancer. And for that, I will be eternally grateful.
Written by Mohammad Alabdulrahman, MED Class of 2026
Everyone, many heys from New York! I just started my pediatric residency at SUNY Downstate, Brooklyn, and I love this place! The weather is bright and shiny – I always admire it, passing by hospital windows. I live in a wonderful place; it takes just 5 minutes to get to the clinic. New York is a grand city with so many things to do – I would definitely go out on one of these weekends. Oh, wait, I’m working 24h and then catching up on my lost sleep. Well, there is always another time… if I get enough energy to muster after work.
Really, it is a lot of work, coming to a new country and starting residency, but I enjoy it. I had the best possible start – I interned in the Nursery, overseeing the treatment of neonates in their first three days of lives. And taking care of the newborns is what sold Pediatrics to me in the first place. I also love continuity of care, meaning that I will follow the same children for the next 3 years, observing their health and helping them grow. And I can attest to how wonderful the feeling is when you see an infant you knew from his first hours of life thriving and developing.
Dr. Nadiya
I like being an intern but can’t wait for the second year when I will have a pediatric oncology rotation at Memorial Sloan Kettering Cancer Center, a leading world cancer for pediatric oncology treatment. Furthermore, it has teams working on treating patients with neuroblastoma and is where research and clinical trial take place. I aim to join one of the projects and continue the work that I started with Dr Olga Piskareva. She taught me to love research and inspired me to improve my skills and reach new highs. I miss my time working with Dr Piskareva and the neuroblastoma lab, both research and social parts, and I hope to see them all soon – at one of the neuroblastoma conferences. 🙂
Huge congrats to a newly minted Dr Catherine Murphy! She successfully defended her PhD work yesterday. Hard work and dedication paid off. Well done, Catherine!
We thank examiners Drs Oran Kennedy and Niamh Buckley for their time and expertise provided.
While completing my Master’s degree at Tulane University in New Orleans, Louisiana, I found the top-notch post-grad comfort food I’ve taken with me ever since. After a day of work, the last thing I want to do is come home and cook an entire meal. Luckily, red beans and rice can be adapted to a slow cooker. Allowing me to throw all my ingredients in and come home to an amazing-smelling apartment with the most satisfying warm bowl waiting for me.
There’s something to the name “The Big Easy” that describes New Orleans because the people and the food take life a bit slower and enjoy every savoury bit together. My favourite memory in New Orleans is when my friends and I prepped a massive stock of red beans and rice for the week of Mardi Gras. This is an entire week of festivities and parade floats where the city quite literally shuts down since everyone participates. It was so comforting every night (or early morning) to come back from the parades and dish out the prepped meal that would fill you up, stick to your bones, and help you fall sound asleep with more than enough energy for the next days of parades.
My first red beans and rice in New Orleans
Red beans and rice is a Cajun dish with Haitian influence and contains the “holy trinity” – bell pepper, onion, and celery. You can find this vegetable blend in the base of almost every Cajun meal, including etouffee, jambalaya, and gumbo. Red beans and rice are traditionally made with a stovetop pot set on a low boil all day. However, the ease of a slow cooker is made with the PhD student in mind as it also keeps well during the week. The most important piece is to get red beans and soak them for about 12 hours before cooking them. This will make the beans more digestible as well as more hearty. Andouille is a Cajun spiced sausage that might be at a speciality butcher shop. Another crucial ingredient, Slap Ya Mama (yes, you read that right), is only available in the U.S. Slap Ya Mama seasoning has its name because “every time a mama uses it, she receives a loving slap on the back and a kiss on the cheek for another great dish”. There are so many great memories I have from my time in New Orleans and I’m happy to share my favorite meal. I hope you are able to replicate this dish and taste the Southern Comfort that is very true for New Orleans.
Laissez les bons temps rouler!
Recipe:
Serves 6, Cook time is 4 –8 hours
450 grams of dried red kidney beans (New Orleans Camelia brand recommended)
450 grams Andouille sausage (or smoked), sliced ½ inch
4 tablespoons olive oil
1 yellow onion, diced
4 ribs celery, diced
1 green bell pepper, chopped
4 cloves garlic
1 bunch green onions, chopped and divided
3 cups chicken broth
3 cups water
1 tablespoon Slap Ya Mama seasoning
1 teaspoon black pepper
1 teaspoon dried thyme
1 teaspoon dried oregano
3 bay leaves
Handful of fresh parsley, chopped
For serving:
Cooked long-grain white rice
Hot sauce
Instructions:
Rinse beans and soak.
Brown sausages in oil on both sides. Set aside.
In the same pan, add garlic and onion, sauté for 2-3 minutes until transparent. Then add the bell pepper, celery, and half of the green onions. Sauté for 5 minutes.
To the slow cooker, add your cooked vegetables. Then add the red beans, black pepper, Slap Ya Mama, dried thyme, oregano, and bay leaves.
Add the water and chicken broth.
Set the slow cooker to high setting for 4 hours or low for 8 hours.
When beans are ready, take out 1 ½ cups to mash and put back in pot.
Remove the bay leaves and add the sausage back in. Cook until sausage is hot.
Serve over a bowl of hot white rice with hot sauce, green onions, and parsley for garnish.
Notes:
In New Orleans, they also add a split-faced grilled sausage to the top.
This can be adapted to an Instant Pot (Pressure Cooker) as well. Just set the pressure to high for 60 minutes with a 15-minute natural release.
If the beans seem too thick, add more water.
This is a great dish that can be stored for a week or frozen for two months.
She successfully defended her PhD work yesterday. Hard work and dedication paid off. Well done, Catherine! 
