Understanding how neuroblastoma develops
In 2019, with Children’s Cancer and Leukaemia Group (CCLG), we awarded £72,656 to Dr Anestis Tsakiridis at the University of Sheffield to help better understand the causes of neuroblastoma.
The team will carry out a series of tests to understand how human trunk neural crest cells become cancerous. This could then lead to further investigations to stop the neuroblastoma cells from developing.
Dr Tsakiridis shares his motivations, why team work matters and tells us more about his exciting work.
“I consider myself extremely lucky that I am surrounded by very talented people, both team members and also collaborators.”
What motivates you in your role at Sheffield?
Passion for discovery and curiosity are my two main motives for doing research. The fact that the knowledge we generate in the lab could also increase our understanding of the causes of devastating diseases such as neuroblastoma is a key additional factor.
What is your background? Why are you focusing on neuroblastoma research?
I trained in stem cell and developmental biology, two fascinating fields that examine how unspecialised cells in the early embryo generate the entire body. Our research group is particularly interested in an embryonic cell population called the neural crest, which normally gives rise to various structures in the body including the part of our nervous system that controls the involuntary function of internal organs.
When neural crest cells fail to develop properly in utero due to mutations, they lose their ability to control their growth and this in turn results in the formation of neuroblastoma tumours. This link between normal neural crest development and neuroblastoma formation prompted us to study further how tumours may arise from “normal” cells.
How many are you on your research team?
At the moment our team consists of seven people (including me). I really want to stress that research discoveries are not possible without the coordinated efforts of entire groups of researchers relying on collaboration and very hard, repetitive work. I consider myself extremely lucky that I am surrounded by very talented people, both team members and also collaborators.
Image of neurons (the cells with the green projections) derived from neural crest cells in the petri dish. These cells do not develop properly in utero when neuroblastoma -associated mutations occur.
Can you explain a little about your research project and what it will involve?
Neuroblastoma arises in utero when neural crest cells become cancerous due to changes in their DNA. One such change results in the presence of very high levels of a gene known as MYCN. This is considered to cause the “transformation” of normal neural crest cells to neuroblastoma.
We have recently developed a method for producing human neural crest cells from pluripotent stem cells in the petri dish. We now plan to test the effect of converting these neural crest cells into cancerous cells resembling neuroblastoma by artificially raising their MYCN levels. We will then try to understand the mechanisms by which MYCN acts to force the transformation of normal neural crest cells.
What do you hope your research will lead to? What impact will it have?
Our work will hopefully shed light into the causes of neuroblastoma and therefore aid the development of novel therapeutic strategies for its treatment.
Read about Dr Anestis Tsakiridis’s research and current research grants awarded in 2019.