Senior Postdoctoral Research Scientist
Primary cilia in pancreatic cancer
My research focuses on how loss of the primary cilium impacts the onset and progression of pancreatic cancer. Primary cilia are microtubule based organelles that regulate cell-cell signalling, in particular Hedgehog (Hh) signalling. Cilia are present on most vertebrate cells, however in many cancers cilia are lost rendering cells incapable of responding to cell signals. The aim of my research is to understand how ciliogenesis is blocked and how cilia loss impacts cancer progression.
I am focusing on pancreatic ductal adenocarcinoma (PDAC), the fifth leading cause of cancer related deaths in the UK. However by 2020, PDAC is predicted to become the second biggest killer. This is because unlike other cancers there has been no improvement in detection and only minimal advances in treatment of PDAC, in the last 30 years.
PDAC is often not detected until the disease has reached an advanced stage and frequently spread, making the average life expectancy of PDAC patients a dismal 4.4 months. If we were able to reliably detect the disease earlier we would be able to significantly improve patient survival. Cilia loss is one of the earliest events to occur in PDAC. I am investigating whether the absence of primary cilia could be used as a biomarker to detect early stage lesions before tumours reach an advanced stage.
PDAC originates from neoplastic lesions within the ductal epithelium or from acinar cells that have undergone acinar to ductal metaplasia (ADM). Metaplastic cells have cilia, allowing them to respond to Hh signals which instructs them to resume their acinar fate. I predict that cilia loss would prevent metaplastic cells from sensing Hh, blocking their normal progression to acinar cells and instead predisposing these cells to transform into early neoplastic lesions.
Ciliogenesis and Hedgehog signalling are supressed downstream of KRas during acinar-ductal metaplasia.
Bangs FK. et al, (2020), Dis Model Mech
EXPLORING AND EXPLOITING A CILIOME-PROTEASE-MATRIX REGULATORY AXIS DISTURBED IN OSTEOARTHRITIS
Collins I. et al, (2018), OSTEOARTHRITIS AND CARTILAGE, 26, S99 - S100
Primary Cilia and Mammalian Hedgehog Signaling
Bangs F. and Anderson KV., (2017), Cold Spring Harbor Perspectives in Biology, 9, a028175 - a028175
Lineage specificity of primary cilia in the mouse embryo
Bangs FK. et al, (2015), Nature Cell Biology, 17, 113 - 122
The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment
He M. et al, (2014), Nature Cell Biology, 16, 663 - 672