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Fiona Bangs is a Postdoctoral Researcher in Eric O’Neill’s lab.

In this interview Fiona tells us about her research on primary cilia in pancreatic cancer, touches on the challenges involved and talks about why studying pancreatic cancer is important for improving patient survival.

 

What is the focus of your research?

I am interested in how the primary cilium influences the initiation and progression of cancer. Primary cilia are immotile antenna like structures that protrude from the cell surface and function to transduce intracellular signals, in particular Hedgehog (Hh) signals. You have a single primary cilium on every cell in your body, bar a few exceptions, however cilia are lost or dramatically reduced in many cancers. Given their importance in cell-cell communication my aim is to understand how cilia loss affects cancer onset and growth.

Currently I am focusing on pancreatic cancer mainly because pancreatic cancer has such a dismal survival rate and also because cilia loss is one of the earliest events to occur in pancreatic cancer.

 Are there any particular challenges?

Aside from the normal difficulties in securing funding, the major challenge has been to develop a model system where we can tease apart the molecular events that lead to pancreatic cancer. We have made significant progress in developing an ex-vivo 3D pancreatic organoid model system where we can induce oncogenic transformation and simultaneously delete genes we believe are important for progression, in my case genes critical for ciliogenesis.

 Why do you think this is important?

Studying pancreatic cancer is extremely important because unlike other cancers such as breast, prostate or bowel there has been no improvement in diagnosis or treatment of pancreatic cancer in 30 years. As a consequence by 2020 pancreatic cancer is predicted to become the second major cause of cancer related deaths, surpassed only by lung cancer.

The symptoms of pancreatic cancer are vague and include abdominal and back pain, unexplained weight loss and indigestion, all things that can easily put down to other much less deadly causes. As a consequence diagnosis normally occurs too late with 50% of patients not identified until the primary tumour has metastasised, often when they walk into A and E. On the rare occasion when the tumour is detected earlier, 5 year survival increases from 5.9% to 56.7%. So it is very clear, if we were able to reliably detect pancreatic cancer earlier we could significantly improve patient survival. The aim of my research is to develop models of early disease and determine what the initiating events are such that we can use these to develop early diagnostic tests. In particular I am focusing on the impact of cilia loss since this is one of the first events to occur in early stage precancerous lesions.

How did you get to where you are in your career today? What input/support from others have you particularly valued?

I did my PhD with Cheryll Tickle, in developmental biology looking at congenital limb defects. I was studying a naturally occurring chicken mutant with polydactyly. I discovered a mutation in a gene that is essential for ciliogenesis. This coincided with the ground-breaking discovery in Kathryn Anderson’s lab that primary cilia are required for Hh signalling, the signal that determines digit number. I then moved to Kathryn’s lab in New York where I spent 3 incredible years. In my work there I was able to demonstrate when and where cilia first appear during development. This led to the discovery that extraembryonic cells actively suppress cilia formation so they cannot respond to Hh signals. I then decided to come back to the UK and joined Eric’s lab. Here I have been asking if loss of cilia in cancer is regulated in the same way as in extraembyonic cells and trying to understand what the implications of cilia loss also renders cancer cells deaf to cell-cell signals including Hh and how this impacts cancer onset and progression.

What motivates you? What gets you up in the morning? 

I have to admit that it’s not my research that gets me up in the morning, it’s normally one of my girls! My motivation is fascination, curiosity, I want to understand how cilia maintain normal cell homeostasis and how cilia loss impacts cancer.

Outside of work, what do you do to relax?

Relax? What’s that? Full time research career and two small children means there’s very little time for relaxing. I do take time out for yoga and when I can I really enjoy getting out on the hills, walking or better still climbing and occasionally I sneak off for a week of skiing!