EACR Travel Fellowships are co-sponsored by Worldwide Cancer Research and provide funds up to €3,000 to early-career cancer researchers. For more information on how to apply for Travel Fellowships, you can visit the EACR website.
Home institution and country: HRI Biodonostia, Paseo del Dr Beguiristain S/N, 20014 San Sebastián, Spain
Host institution and country: Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, John Radcliffe Hospital – University of Oxford, UK
Dates of visit: 09 April 2018 – 08 July 2018
My PhD project is focused on discovering novel miRNAs as predictive biomarkers of R-CHOP resistance. R-CHOP treatment is based on anthracycline drugs in association with rituximab (an ant-CD20 chimeric human-mouse antibody). Despite the great progress obtained during the last decade, one-third of DLBCL patients either directly fail to respond to R-CHOP (i.e. innate resistance) or suffer a relapse (i.e. acquired resistance). The resistance occurs because different mechanisms are activated to evade induced apoptosis or also due to a large inactivation of chemotherapy drugs. These mechanisms are regulated by miRNAs and it is demonstrated that they are regulators of the activity of different anticancer drugs, as well as the resistance to those drugs.
How did you hear about EACR Travel Fellowships?
I heard about EACR from a postdoctoral fellow in my lab. She was telling me about the many opportunities I could take advantage of, if I became a member and one of them was the Travel Fellowship programme. My home supervisor always told me that one of the career steps for a predoctoral student should be to have a scientific exchange abroad.
Why did you choose the host lab?
For those reasons, I decided to step forward and start to have contact with Prof. Banham at the Nuffield division of clinical laboratory sciences (NDCLS), at JR hospital in Oxford. The laboratory has extensive experience in DLBCL study, as well as validating antibodies for those target genes that do not yet have fully characterised detection reagents available. The department has a large collection of suitable cell lines and they have already optimised RNA interference by using siRNA for different genes in those DLBCL cell lines that I used in my laboratory.
Can you summarise the research you did or what you learned on your visit?
Our preliminary results, using both miRNAs and gene expression microarray, have shown different miRNAs and genes that can contribute to the resistance. Several of these miRNAs can regulate different targets, which are involved in different critical steps of lymphomagenesis and one of those, FOXP1, is a critical transcription factor whose deregulated expression makes important contributions to DLBCL pathogenesis. In this collaboration, I used tissue microarray from DLBCL patient samples and I stained the sections by immunohistochemistry and for those markers, I would implicate in the acquired resistance to R-CHOP. Moreover, I have used the RNAi to understand how FOXP1 is involved the resistance to R-CHOP. Finally, I used a depletion model of FOXP1 in A20 cell line to understand how the lack of this gene can influence the acquiring of R-CHOP resistance.
Describe a ‘typical day’ on your visit.
Normally, I started my work day at 8:30am – 9am, to end the day at 6pm at the latest. I was living just near the John Radcliffe Hospital, at the Ivy Lane work houses, so I travelled to work in five minutes by walk: it was a great choice in terms of health and time. The apartment was cosy, simple and it served my needs very well. I normally worked between the office, where I had my personal post with my PC and the laboratory with my bench. I socialised with other colleagues in the department and it was a routine to go to the pub to eat, drink and talk after work.
Was the host institution very different from your own, and was there anything you particularly liked about the host institution?
The NDCLS is a very important department in the University of Oxford, and Prof. Banham is the head of the department. She is an important and internationally recognised expert in cancer research and her work at the NDCLS is primarily focused on studying the transcriptional deregulation of B-cell malignancies and the development of novel antibody for cancer therapy. The department is quite old and so is very well equipped, with an enormous collection of cell lines. What I appreciated most was the diversity within the institute: there were a lot of fellows from all over the world, which meant you could share ideas and absorb knowledge about science with many different people from various cultures.
Does your lab plan to do any future collaboration with the host lab?
As we all know, science can be very satisfying but also at times, terribly disappointing. Therefore, you must be prepared to recalculate your goals as much as you are encountering problems or embracing new ideas whilst on your stay abroad. Sharing my previous results with NDCLS enabled us to reach the conclusion that JAG/NOTCH, another signalling pathway, could be interesting to investigate. Massimo Masiero, one of the postdoc fellows that I thank, helped me with this and we designed different experiments to try to understand how to involucrate this pathway in my resistance model, using a monoclonal antibody, anti-JAG1, that they have recently developed. The results obtained with my in vitro model are very promising, so we will continue this collaboration using a mice model KO for JAG1 they have already developed, xenotransplanting our resistance cell in those mice, treating them with the antibody anti-JAG1 and whether we can reduce the development of the tumour.