Cell Communication and Signaling Dysregulation in Cancer

Caroline Hill is a Senior Group Leader of the Developmental Signalling Laboratory and an Assistant Research Director at The Francis Crick Institute, UK. Caroline studied for her Ph.D. in the laboratory of Jean Thomas at the University of Cambridge.

Here, she shares insight into cell communication and signaling dysregulation – her area of expertise. Her research group are focused on understanding the signals sent to, and sent by cells – and how this communication influences cellular behavior. As well as touching on her research, Caroline discusses the evolution of cancer and suggests strategies for encouraging more women to pursue a career in STEM.

Laura Lansdowne (LL): What motivated you to pursue a career in science?

Caroline Hill (CH): I first had the idea of becoming a scientist when I was about 10 or 11 years old, when I read a biography of Marie Curie. I relished the idea of working in a lab and discovering things that no one else knew. Even as a small child I also loved doing practical things – cooking, gardening, woodwork, so honed my practical skills that way. At secondary school I really enjoyed maths, physics and chemistry and had a natural aptitude for these subjects. I intended originally to become a physicist, but worked in a hospital biochemistry lab in my gap year before I went to university and that was when I realized that what I really wanted to do was medical research. This passion grew during my time as an undergraduate at the University of Cambridge and I specialized in biochemistry at the end of my degree course.

LL: Could you tell us more about your current research interests and area of expertise?

CH: My major research interest is cell communication. We study how one group of cells sends out chemical signals to neighboring cells that change their behavior, for example their growth rate, their shape, their ability to move, or their identity. This phenomenon, which is called cell signaling, is essential for embryonic development, the process whereby a single cell (the fertilized egg) develops to eventually become a complex newborn animal. Crucially, cell signaling goes awry in human diseases, most notably in cancer.

The particular signals that my lab works on are required for specifying different types of cells in the embryo and for patterning the embryo, and they also play critical roles in driving both the initiation and spread of tumors in humans. With regard to the embryology side of our work, we focus on zebrafish embryos, which are simpler to study than humans, but share many of the same processes. We want to understand how cell communication determines what types of cells are specified at the early stages of embryonic development and how this leads to intricately patterned fully functioning tissues later in development. This is not only important from the discovery point of view, but is important for developing methods to engineer tissues for organ repair in adults. With respect to cancer, we are trying to understand how mis-regulated signaling leads to the growth and spread of tumors. We are also developing therapeutics to inhibit this signaling, which we hope might result in the clinical development of novel drugs for treating different types of cancer.

LL: Are there any areas that you are yet to explore that you would be eager to investigate in the future?

CH: Mis-regulated signaling by the proteins that we work on not only results in cancer, but can also lead to other diseases, in particular, the so-called Marfan-related syndromes. These are syndromes that affect bone growth and the cardiovascular system among others things, and result from mutations occurring in proteins that are responsible for communicating the signals we are interested in in the target cells. We have just started to explore these diseases with a view to being able to develop therapeutics to help patients manage their symptoms, and even reverse some of the detrimental effects of the mutations.

In terms of cancer, if we are successful with the therapeutic strategies that we are developing, we want to explore which different cancers they may be relevant for. This is very exciting, as we have some evidence to suggest that the mis-regulated signaling we are investigating might be a fairly widespread phenomenon.

LL: How has our understanding of cancer evolved since you began to work in the field?

CH: Our understanding of cancer has grown hugely since I first started working in the field in the early 1990s. First of all, we have a much better idea now about the range of mutations that drive tumor formation and spread from our ability to sequence genomes.

By understanding the different signaling pathways that drive tumorigenesis, we have also been able to develop much more specific chemotherapies to halt tumor growth and metastasis. Because they are more specific, they have fewer side effects than the more traditional broad-spectrum chemotherapies. The final big leap forward has been a much better understanding of how the tumor influences the immune system to prevent it from recognizing and killing tumor cells. There are now therapies that will reactivate the immune system in the context of cancer, resulting in a renewed ability to attack and kill tumor cells. In fact, we hope that the therapies that we are developing will act in concert with these so-called immune therapies.

LL: What can be done to inspire more women to pursue a career in STEM?

CH: Having diverse role models for girls throughout their education and in the STEM career itself is very important. I think it is essential that girls see women succeeding in STEM careers. They will then realize that this is a career that they too can pursue. Providing work experience for girls at school and university in STEM jobs is part of this. It is also very important that women are chosen as experts to discuss science in the media, whether that is TV, radio or in the written media. Too often men are solely used as experts in these contexts. This gives girls and young women the idea that science is not a job that women tend to do.

Having women presenting science shows on TV is also excellent for showing girls that women are just as capable and likely to be scientists as men. In recent years several women have presented the Royal Institution Christmas lectures (Alice Roberts, Hannah Fry), which I think is great. Science as a profession still has some way to go in terms of equality between men and women. It is more out in the open now than it used to be and there are various ways that things can be improved. An obvious one is unconscious bias training for all people involved in hiring. It is clear that people often hire in their own image. It is important that people are aware of this and value all different types of personalities and approaches.

Caroline Hill was speaking with Laura Elizabeth Lansdowne, Senior Science Writer for Technology Networks.