Biomarker update from Imperial College

In 2011, AMMF made a grant to Imperial College London to fund the work of Research Fellow, Dr Abigail Zabron, for a year. Abigail has now sent us an update on her work into cholangiocarcinoma biomarkers and on what is happening in the laboratory, and we are delighted to report that we have agreed a further grant to Imperial College to secure her second research year.

“Over the past few months we have recruited more samples from patients with cholangiocarcinoma undergoing ERCP. The increased number means that we are able to run similar proteomics experiments to those we have previously had success with, but looking specifically at CC, aiming to find proteins that can act as bile biomarkers of CC. This is something we have been aiming to do for a long time, so having enough samples to do this now is very exciting. The samples should be loaded onto the analytical instrument next week. We have a Master’s student keen to do some preliminary data analysis before she finishes next month, although full analysis will take rather longer and then needs further work to confirm findings. I will be looking at these samples for the previously identified biomarker, NGAL, to see how the levels compare between pancreatic cancer and CC.

In parallel, we have been looking at blood samples to extend our preliminary findings of blood markers. Last summer Dr Chris Wadsworth and Dr Verena Horneffer van der Sluis found elevated levels of a protein that is an enzyme by looking at the proteins present in blood. We have been trying to confirm this by doing an assay* for the activity of the enzyme rather than looking for the protein molecule – in theory this could tell us more than looking at protein molecule levels. Developing this assay has not been as straightforward as we were hoping, but we are getting to the point where we will soon have definitive data, and can use other methods if the meaning is still not clear.

I have also run some preliminary experiments with a colleague in another group looking at levels of miRNAs in bile. There are some other reports in the literature on this, but certainly this is an under-explored area, and one that utilises existing samples. The initial work has confirmed we can make the technique work, and find sensible differences in molecules identified by others as being of biological importance. So the next stage is to take this forward in more samples/ looking for other markers.

We have a couple of other collaborations we are developing within Imperial, one group wanting to use the samples from our patient group to look for a protein they have identified in a different sort of cancer to see if it is raised in CC, and another hoping to involve us in developing targetting molecules to deliver imaging dyes or therapy to CC cells – this is very, very early stages though.

I am going to the Mayo Clinic soon, to spend 4 weeks observing in their lab to hopefully get some insider tips on the cell line work we want to do, and to help them set up bile collection as collaborators in our study. This is under the Sheila Sherlock Travelling Fellowship in Hepatology programme, which is designed to foster research and clinical experience. The lab experience will be invaluable in getting the most out of my remaining time in research, and obviously developing collaborations with their group could make a big difference in developing our work.

I will also get the chance to spend time in the clinical setting and want to learn as much as possible about the transplant programme, and clinical diagnostics, eg FISH. This is the perfect opportunity.”

* An assay is an investigative (analytic) procedure in laboratory medicine, pharmacology, environmental biology, and molecular biology for qualitatively assessing or quantitatively measuring the presence or amount or the functional activity of a target entity (the analyte) which can be a drug or biochemical substance or a cell in an organism or organic sample.