5th Neuroblastoma Research Symposium, Cambridge, 11-12th April 2019

Here, we are – the Irish neuroblastoma research team landed at the 5th Neuroblastoma Research Symposium in Cambridge. Four poster presentations by four enthusiastic scientists. The two days crash course in neuroblastoma – vibrant, intense, informative.

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!

Dream Team in Action: Olga, John, Ciara & Tom

SYMPOSIUM PROGRAMME
THURSDAY 11TH APRIL
12:00 – 13:00 Registration, lunch & poster setup

13:00 – 13:10 Introduction – Neuroblastoma UK & CRUK Cambridge Centre

Session 1: Neuroblastoma biology & prognosis

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

16:45 – 17:00 Combined discussion

17:00 Close

Hot Chocolate Morning In Aid of ICCD2019

Across countries and continents, we are celebrating International Childhood Cancer Day (ICCD).We do it to raise awareness tto raise awareness of childhood cancer, its consequences for children and their parents and make it as a priority for Governments and research.

My team research is focused on neuroblastoma biology. This is a solid tumour of undeveloped nerves. Some forms of neuroblastoma spread quickly and become very aggressive and challenging to treat. We are searching for the weaknesses that can be targeted with drugs.

Ciara, John, Tom, Nele and Olga

Today, we team up with Amorino to run the Hot Chocolate Morning to raise funds for Childhood cancer research charities – Children’s Medical Research Foundation/National Children’s Research Centre and the Conor Foley Neuroblastoma Cancer Research Foundation. Research advances our knowledge and helps to develop new treatments.

A guessing game was a part of the event. Everyone had a chance to guess how many marshmallows fitted in the cell culture flask T75. The guesses ranged from as low as 95 to as high as 500. Fortunately, one of the participants gave an absolutely correct answer. Micheal Flood put on 173 and won. Her fantastic ability to guess is incredible! Congratulations!!! Well done to all!

We raised 698.91 Euros for childhood cancer research! We thank everyone who came along and supported the Hot Chocolate Morning & the International Childhood Cancer Day 2019!

Many special thanks go to Amorino for delicious Italian hot chocolate & tasty bites contributors!

“Please visit us in St Stephens” Green”

International Childhood Cancer Awareness Day – February 15th 2019

International Childhood Cancer Day (ICCD) was founded in 2002 by Childhood Cancer International (CCI). Each year on February 15th we unite together to recognise childhood cancer as a national and global child health priority & to raise support, funding and awareness of this devastating desiease.

This year we team up with Amorino to run Hot Chocolate Morning.  Please come along! All proceeds go to CMRF/NCRC and CFNCRF.

If you can’t join us, you can simply follow the link and donate ‘a cup of coffee/hot chocolate’ to CMRF Crumlin, the Conor Foley Neuroblastoma Research Foundation & Childhood Cancer Foundation


Scientific part of my journey

Reading my posts, it looks like I am more enjoying the cultural part and almost forgot the main reason I crossed the Atlantic with the Fulbright wings.

The first month in the lab was more a warming up. Where is my desk? Where is the cell culture rooms? How do they run it? How different is it? So, many microscopes – am I capable of imaging? And so on and so forth…

My typical day starts at 8-8.30 am and finishes once all is done. It may be 6pm or 10pm. Once the experiment is set up, I have to monitor cells every 24 hours for 5-7 days with no weekends or days off. The monitoring includes imaging. Lots of imaging. Every condition has 20-30 single cells to follow up. Each cell gets its own GPS tag manually to be able to image exactly the same cell as it grows and becomes a group of hundreds by multiplication. For example, I am running 8 different cell lines in 3 experimental conditions. So, 20-30 cells per all 24 combinations give us 480-720 individual cells to follow up. The imaging takes ~5 hours every day. After 5 days, I will have 2400 – 3600 pics of cells to analyse. It will be fun! I may need lots of Guinness to fly through that numbers.

Tagging cells. The left arrow points to a group of neuroblastoma cells. The arrow in the middle point to the same cells, but this image allows you to see the actual number of the cells. This group has 8 cells. The right arrow points to individual GPS tags for each cell

At the next step, I will select some of the conditions for video recording to trace cell fate from a single neuroblastoma cell to a metastatic niche consisting of hundreds of them. This video will show me how it all happens minute after minute.

Is not it exciting? I am thrilled!

 

Every child deserves a happy childhood

Three girls fountain in Mainz Germany

Last year I have selected this photo of a lovely fountain capturing 3 girls under umbrellas (Drei-Mädchen-Brunnen) in Ballplatz Mainz in support of #ChildhoodCancerAwarnessMonth. This fountain was built between two Catholic girl’s schools symbolising the separate education and a happy childhood. It is charming on its own. And I’ve select it again.
Every child deserves a happy childhood. Raising awareness about childhood cancer we help to make the dreams of children with cancer come true. Dreams for a happy childhood, better treatment, better quality of life full of love ahead through better funding of childhood cancer research and access to innovative treatments.

September is Childhood Cancer Awareness Month!

Today marks the start of Childhood Cancer Awareness Month.

Three girls fountain in Mainz Germany 

The cause of childhood cancers is believed to be due to faulty genes in stem cells that give rise to nerves, skin, blood and other body tissues. For some unknown reasons, the faulty genes can sit quiet and show their ‘bad’ character after birth and programme the cells into cancer cells.
So, there is no evidence that links lifestyle or environmental risk factors to the development of childhood cancer, which is opposite to many adult’s cancers.

Every 100th cancer patient is a child. Cancer is the 2nd most common cause of death among children after accidents.

Children are not little adults and so their cancer. Some childhood cancers have a good outlook and successful protocol of treatments. However, some of the cancers do not respond to the known drugs, or if respond cancer cells find the way to develop resistance and come back being more aggressive. Among theme are some forms of brain tumours, neuroblastoma and sarcomas; cancers developing in certain age groups and/or located within certain sites in the body, along with acute myeloid leukaemia (blood cancer). Children with a rare brain cancer – diffuse intrinsic pontine glioma survive less than 1 year from diagnosis. Children with soft tissue tumours have 5-year survival rates ranging from 64% (rhabdomyosarcoma) to 72% (Ewing sarcoma). Less than50% of children with the aggressive form of neuroblastoma will live beyond 5 years with current treatment strategies.

For majority of children who do survive cancer, the battle is never over. Over 60% of long‐term childhood cancer survivors have a chronic illness as a consequence of the treatment; over 25% have a severe or life-threatening illness.

The most common types of childhood cancer are:

  • Leukaemia and lymphoma (blood cancers)
  • Brain and other central nervous system tumours
  • Muscle cancer (rhabdomyosarcoma)
  • Kidney cancer (Wilms tumour)
  • Neuroblastoma (tumour of the non-central nervous system)
  • Bone cancer (osteosarcoma)
  • Testicular and ovarian tumours (gonadal germ cell tumours)

Please see a short video The Childhood Cancer Ripple Effect created by St. Baldrick’s Foundation.

A new, three-dimensional approach to cancer research

Appeared in today’s Irish Times. Lovely crafted by Dr. Vanesa Martinez

Although the discovery could be applicable in principle to any a solid tumour, Dr Piskareva’s target is neuroblastoma, a relatively common child cancer which affects a specific type of nerve cells in unborn children. “It’s quite aggressive and unfortunately there are many children who have metastasis when they are diagnosed, and this is the most challenging group to treat.”

Irish Times, 31 May 2018

https://www.irishtimes.com/news/science/a-new-three-dimensional-approach-to-cancer-research-1.3505347

Groundwork

Though the official announcement is scheduled for the first week of June, the groundwork is on. Lots of reading and planning for the trip to Johns Hopkins later this year. One of the first is the book by Rebecca Skloot ‘The Immortal Life Of  Henrietta Lacks”. The famous HeLa cells were generated by researchers at JH. The story is a fascinating journey for biomedical scientists and a tragedy for the Lacks family.

A new 3D strategy to study neuroblastoma

Our body has 3 dimensions: height, width and depth. Every single part of our body grows in the same 3 dimensions. This is true for cancer cells. Researchers use different ways to study cancer cells behaviour, how they grow and spread. We grow cells in the flasks, where they change their structure and shape and become flat losing one dimension. This is a very popular approach. We also grow cells in mice, where cells keep their 3D shape and mimic their behaviour to one observed in humans.

It is well known that we need to give a different amount of drug to kill cancer cells grown in flasks and in mice. This, in turn, delays the development of new drugs. Why does it happen this way? So, the drug works only on one side of the cell when they grow on the flat surface. In contrast, in mice, drug surrounds the cancer cell habitat and attacks cells at the edge first and then getting to those at the core. So we need more drug to kill cancer cells in mice.

We decided to design a new way to grow cancer cells that recreate their growth in 3 dimensions as in the human or mice body. We used special cotton wool like sponges as a new home for cancer cells and populated them with cancer cells. At the next step, we gave cells the drug at the different amount and checked what happened.

To understand cell fitness we stained them with red and blue dyes. On the left bottom side of the image, we see an equal amount of red and blue dyes telling us that cells were healthy and fit. Cells did not get any drug. When we gave a little amount of the drug but enough to kill cells in the flask, the balance of red and blue dyes was the same telling us that nothing really happened (the image in the middle). Cells were feeling well and healthy. The right bottom image has only blue dye. In this case, cells were given the amount of drug enough to destroy cancer cells in mice or humans. The lack of red dye tells us that this time the drug worked and killed the cancer cells.

We found that the drug killed cells on sponges only at doses enough to do the same in mice.

So, we concluded the new tactic to grow cancer cells in 3D on cotton-like sponges can bridge the gap between traditional way and animal models. This new strategy to grow cells on sponges should help to understand cancer cell behaviour better and accelerate the discovery and development of new effective drugs for neuroblastoma and other cancers. This, in turn, will make the outlook for little patients better and improve their quality of life.

This work has been published in Acta Biomaterialia and presented recently at the Oral Posters Session at the 54th Irish Association for Cancer Research Conference 2018.

This study was supported by Neuroblastoma UK and National Children’s Research Centre.

You can find more at

A physiologically relevant 3D collagen-based scaffold–neuroblastoma cell system exhibits chemosensitivity similar to orthotopic xenograft models.

IACR Meeting 2018 Programme

Goodbye 2017! Hello 2018!

When I look back on my journey in 2017, there were many junctions, traffic lights and stops as well as ups and downs. Junctions were to make decisions, while traffic lights and stops – to be patient. Ups and downs were my feelings of satisfaction. The good mix of both kept me to stay human. It is not the number of grants received that matters it is who around you. I have met genuinely curiosity-driven students who made this journey fascinating and very special.

My most memorable Ups  were the successful examination and graduation of my PhD student John Nolan, organisation and chairing the IACR Meeting session: Challenges in Childhood Cancers, the Mad Hatter’s Tea Party and the Gala Dinner with the CFNCRF, the launch of my very own research team thanks to the funding by the NCRC and the Neuroblastoma UK, the successful completion of two final year undergraduate and two MSc projects, and welcoming the new PhD student Tom Frawley.

My team is growing and I am looking forward to 2018!

Goodbye 2017 and Hello 2018!