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

Halfway through

Can you control the time? I can’t and know none who can. It flies, when things around you work out, and drags on when not. The time flies for me here in Baltimore. It feels so intense sometimes and then slightly slows down. I take pictures almost of everything: the path’s signposts when rambling in the network of Johns Hopkins Buildings, the first frosty morning, joyful deer at the backyard of my host family house, outdated clothes in the shop…

In the past, I had a similar journey to Ireland. It was 3 months research placement during my PhD. Did I like it – oh, yes I did! I travelled a lot, felt romantic and changed my life on my return home. But I did not run a diary or tag my way on Facebook. I have learnt the lesson: do it even more intense as you can’t travel back in time and write down your experience. It may be funny or educational to read in a couple of years!  I become addicted to it though not always have time to do it.

I like the people who I am working with. They are a fantastic bunch of self-motivators and open-minded personalities. They are workaholics either naturally like me or because of the exciting projects they do like I do. Who knows, but very likely because of both. Isn’t it a dream to have an exciting project and great people around you? The luck like this gives you wings.

The American enthusiast studying Russian and my Mum

The host family – is my other great luck! This luck was crafted as a parallel story when none knew how the Fulbright application and an American enthusiast learning Russian may intersect. You would not believe, but parallel lines can be non-parallel sometimes! His journey to my home city in Russia paved the way to the opportunity to stay at his aunt’s house.

Every day 50 min drive to and from Hopkins opens up the other side of the local lifestyle and infrastructure. What are the rush hours? How many drivers are signalling before taking a turn? How do they call the shopping trolley?  How parking system works?

Experiencing life as an American working in Baltimore.

 

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.

Saying Good Bye to Our Summer Students

When I look back at the end of July, I am always surprised how quickly 8 summer weeks passed by. Summer students usually come very shy and uncertain and then they are flying through many complicated research terms and techniques. We help them to learn and they pay back by fantastic enthusiasm, commitment, and hard work. This summer was the same!

One of our experiences was donut’s tasting. We tasted donuts from Boston Donuts, the Rolling Donut, Boomerang Donuts and Krust Bakery. Many shapes, textures, and tastes. Krust Bakery did our favourites. 🙂

Saying Good bye to our summer students

 

8th OLCHC RESEARCH & AUDIT CONFERENCE

This was our 2nd time attending the OLCHC Research & Audit Day on May 25th, 2018. The conference provides a great forum for paediatric clinicians to share and update knowledge across different specialties through talks and poster presentations. It is insightful for basic biomedical researchers like us to see other perspectives.

I was delighted to know that two our studies were shortlisted. It is a rewarding feeling to see your Dream Team doing very well. One was the project of the Erasmus+ student Hanne Pappaert and the other was the project of NCRC funded Postdoc John Nolan. Hanne explored our 3D tissue-engineered model of neuroblastoma using collagen-based scaffolds with distinct mechanical properties. These new scaffolds were designed and manufactured by our collaborator Dr Cian O’Leary from Pharmacy Department and Tissue Engineering and Research Group (TERG) headed by Prof Fergal O’Brien. Hanne grew 5 neuroblastoma cell lines on the 3 scaffolds: hard like a rock, soft and fluffy like a cotton wool and a jelly-like. All cells liked the jelly-like environment. This environment is similar to bone marrow – the most common site of neuroblastoma metastasis. We were excited to see the difference as it means we are one step closer to reconstruct this type of tumour spread.

John has expanded our exploration of our 3D neuroblastoma model by examining the content of exosomes – little parcels sent by cancer cells in 3D and as tumours grown in mice.  We were thrilled to see a high similarity in the exosomal content. This finding additionally proved the great applicability of our 3D model as a tool to study neuroblastoma.

 

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.

How current IT advances help in research?

Here is the perfect example of the teamwork troubleshooting protein extractions. My Dream Team 2018 in action. The current information and communication technologies allow to stay connected and respond quickly.

Five minutes later in the lab: troubleshooting is the exchange of experiences!

 

The First Big Challenge in New Year

The first month of the new year and the first challenge. Monday is the big day for me. In the essence, my grant application was shortlisted for the interview where I have to face the challenge and prove that I worth it.

Anyone for a challenge?

The proposed application seeks to go to the US lab and gain an expertise in an interdisciplinary methodology to monitor and capture the dynamic of cancer spread (metastasis) in real time. This experimental approach would accelerate our understanding of neuroblastoma metastasis which is one of the reasons for failure in the treatment of neuroblastoma. If we know how neuroblastoma cells spread, then we can find the weaknesses in the process and create new drugs or use existing to target it.

I feel that sharing my worries with you makes me stronger. I am looking forward to this challenge with my head up and hope to feel your support at this crucial moment.

 

 

 

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!