David Gómez Peregrina is a PhD student at the Vall d-Hebron Institute of Oncology (VHIO) in Barcelona, Spain who received an EACR Travel Fellowship to visit and work at the Barts Cancer Institute in London, UK between May and October 2023.
The EACR is supported by Worldwide Cancer Research to provide Travel Fellowships of up to €3,000 to enable early-career cancer researchers to gain new skills through a short-term visit to a lab or research group in another country.
You can read about other Travel Fellows and their experiences here.
Name: David Gómez Peregrina
Job title: PhD student
Home institute: Vall d-Hebron Institute of Oncology (VHIO) in Barcelona, Spain
Host institute: Barts Cancer Institute in London, UK
Dates of visit: 03 May – 27 October 2023
Research: Chromosomal instability (CIN) drives cancer progression by promoting metastasis, immune evasion, and chemotherapy resistance. Gastrointestinal Stromal Tumours (GIST), the most common sarcoma subtype, have been traditionally considered genomically simple, but recent data shows them as a unique context for studying CIN. GIST exhibits extensive chromosomal rearrangements, DNA copy number alterations, and whole genome duplications, yet the driving mechanisms remain unknown. Our research aims to comprehensively understand the molecular mechanisms driving CIN in GIST, understand the impact of CIN in therapy adaptation, and find vulnerabilities to develop novel therapies in GIST patients.
Why did you decide to apply for an EACR Travel Fellowship?
I decided to apply for an EACR Travel Fellowship for several compelling reasons. First and foremost, the Fellowship presented a unique opportunity to enhance my research skills and expand my academic career horizons. Travelling and living in a city as dynamic and expensive as London can be cost-prohibitive for many aspiring researchers. This grant ensures that financial constraints do not hinder individuals like me from gaining international research exposure, fostering scientific collaborations, pursuing invaluable networking, professional and personal experiences, and contributing to advancements of research projects from PhD students and therefore of the cancer research field.
How did you choose the host lab?
Dr. McClelland’s lab at Barts Cancer Institute (Queen Mary University of London) is a
worldwide reference research group in chromosome instability (CIN) and cancer, focused on studying non-random chromosome miss-segregation patterns, replication stress and the molecular mechanisms underlying CIN. Her team has implemented a wide range of methodologies and assays to routinely study CIN-associated properties in diverse cancer
models, which has enabled a rapid translation of these approaches to our gastrointestinal stromal tumour (GIST) models. Accordingly, Dr. McClelland’s lab was the ideal destination to continue our research project of CIN in GIST biology, expand new skills and knowledge and get involved in projects that will lay down future research lines and collaborations between our teams.
“I am confident that this experience will open doors and have a significant impact on my future academic development”
Can you summarise some of the research you did?
The knowledge gap pertaining to CIN in GIST cell lines and their potential as a
framework for studying the driving and tolerating molecular mechanisms of CIN in GIST is a pressing issue. CIN mechanisms can be broadly classified into “mitotic defects” (occurring during mitosis) or “pre-mitotic defects” (prior to mitosis) during the cell cycle. Through high-resolution microscopy, we have delved into understanding the causes of these errors. Mitotic defects often lead to whole chromosomes lagging during anaphase, referred to as centric chromosomes. Conversely, errors in DNA replication or repair can result in the formation of “acentric” chromosome fragments or chromatin bridges lacking centromere signals. We have also investigated centrosome abnormalities linked to higher rates of chromosome missegregation. Aberrantly segregated broken chromosomes during mitosis contribute to increased micronuclei formation.
Consequently, we have established correlations between missegregation errors and
micronuclei formation in GIST models. Additionally, to assess DNA repair defects and increased DNA damage, we’ve studied the formation and resolution of DNA double-strand breaks and single-stranded DNA foci. Finally, we have assessed the copy number alteration (CNA) evolution caused by ongoing CIN in single-cell derived clones from GIST cell lines and analysed their mechanistic causes by single-cell low-pass whole genome sequencing.
Describe a typical day on your visit.
In the morning, my lab routine began with meetings, either with my supervisor or colleagues, where we delved into the intricacies and nuances of various experimental assays for the ongoing project. These discussions were essential for fine-tuning our approach and ensuring we covered all potential corner cases. Afterwards, I prepared samples for immunofluorescence and other assays that were crucial steps in evaluating
CIN readouts across different experimental setups. Additionally, I spent a significant amount of time in the tissue cultures room, where I worked on maintaining GIST cell
lines and setting up experiments.
In the afternoon, I usually dedicated a substantial portion of my time to analysing
microscopy images, meticulously scrutinising the results of the experiments. I also invested several hours in capturing images from multiple slides across different experimental setups. Additionally, a portion of my day was devoted to my main project, where I analysed the multiomic data from our GIST patients’ cohort. Furthermore, I also contributed my expertise in bioinformatics to other lab projects, providing guidance and support. As the day came to a close, I took time to reflect on my progress and challenges, seeking opportunities for improvement and furthering my research goals.
What were you able to do that you could not have achieved in your home lab?
One of the main reasons for successfully achieving many of the challenges we had set
for this project is primarily attributed to the team’s extensive knowledge of the methodologies and techniques routinely used in Dr. McClelland’s laboratory. Without access to this know-how and the technological resources and reagents, our proposal would have entailed a substantial investment of time, effort, and numerous unsuccessful attempts to obtain results even remotely comparable to those achieved during the stay.
Furthermore, my involvement in the experimental aspect of my project and the invaluable insights and advice from all my colleagues and my supervisor have allowed me to refine many ideas and refocus a significant portion of my project. This effort aims to steer the trajectory of my projects towards generating new ideas and knowledge, which will significantly expand the scope and impact of my work in the field of GIST research. This encompasses various aspects, including the disease’s evolutionary dynamics, the exploration of new candidate mechanisms for tumour progression, driving CIN and therapeutic adaptation, as well as the identification of new molecular vulnerabilities and potential therapeutic targets.
Have you brought back any specific knowledge or technique that has benefited your home lab?
Despite having proposed an ambitious project for the duration of my stay, a significant portion of the objectives has been successfully achieved. However, after conducting multiple experiments, new questions have arisen that need the application of the techniques and methodologies employed during my stay. For this reason, a substantial part of these methodologies will be implemented upon my return to my home lab. For example, all the methods used to assess CIN readouts based on high-resolution microscopy quantification of chromosome segregation errors, centrosome abnormalities, micronucleus formation, and DNA damage, will be implemented to ensure the proper continuation of my projects. Furthermore, I have learned to perform metaphase spreads and quantify DNA content with fluorescent diploid controls by FACS, which will also be of great importance in validating ploidies in other cell lines of different sarcoma types. In conclusion, we will not only implement these experimental protocols but also enhance some of them to acquire more comprehensive insights into various aspects of chromosomal instability in GIST and other types of sarcomas.
Was there anything you particularly liked about the host institution?
From the very beginning, both my laboratory colleagues and those from other departments at Barts Cancer Institute have been incredibly welcoming and hospitable. I have been pleasantly surprised by the multitude of social events organized at the institute, all with the aim of helping PhD students connect and share their scientific experiences. Furthermore, Barts regularly promotes seminar sessions and educational talks, both from the academic and pharmaceutical industry. These sessions have added significant value and offered intriguing insights into various aspects and knowledge domains within the field of biomedical cancer research.
Another aspect that has amazed me about Barts is that, unlike many other research centres in London, it is situated on an enviable campus with green areas for dining and relaxing after a day’s work. I’ve had the chance to enjoy the summer sun in these pleasant surroundings.
Did you have a personal mentor or anyone who particularly helped you?
Indeed, Dr. McClelland has been one of my greatest sources of inspiration in gaining a better understanding of chromosomal instability from an experimental standpoint. She consistently shared incredibly innovative ideas with me, which ultimately had a profound impact on shaping my own ideas and, consequently, my scientific projects. Another team member with whom I’ve spent a significant amount of time and whom I regard as a mentor is Dr. Nadeem Saikh. He has provided invaluable guidance on the technical and scientific aspects of all the assays I’ve conducted during my stay. Right from the outset, I have felt a tremendous degree of freedom to tailor my scientific activities in the lab based on my questions and the requirements of the proposed project. All of this has only been possible thanks to the invaluable teachings, attention, and trust extended to me by Dr. McClelland, Dr. Shaikh, and the rest of the team.
Did you take part in any interesting cultural activities?
The day after my arrival in London, I had the opportunity to attend what I consider the
most British event I’ve ever been to, the coronation of King Charles III of England. After
several hours of waiting and wandering around St. James’s Park, I finally managed to
catch some glimpses of the procession from Westminster Abbey to Buckingham Palace. Unfortunately, shortly after, it started raining heavily, and I had to leave the event to take shelter. A very British experience.
What was a personal highlight of your trip?
Undoubtedly, this has been one of the most rewarding experiences I have had while working in a foreign laboratory. From the very beginning, both Dr. Sarah McClelland and her entire team have welcomed me with exceptional warmth, attention, and hospitality. I have had the privilege of meeting wonderful people in the lab from whom I’ve learned a great deal, not only in terms of technical and scientific aspects related to chromosomal instability but also in other facets of life in general. They have placed a lot of trust in me, allowing me to actively participate in various projects of theirs where I’ve been able to contribute significant value with my skills and knowledge in bioinformatics.
Furthermore, Dr. McClelland has shown a keen interest in my projects and has been highly involved in them, providing me with fresh perspectives and approaches that will undoubtedly enhance the chances of my research being published in a high-impact journal.
How has the trip inspired you in your research?
The trip has been a remarkable source of inspiration for my research on multiple levels. First and foremost, the people I’ve encountered during my journey have been instrumental in broadening my perspective and fuelling my enthusiasm for scientific exploration. Interacting with colleagues and experts at the host institution, as well as fellow researchers from various backgrounds, has allowed me to engage in thought-provoking discussions, exchange ideas, and gain fresh insights into my field of study.
The diverse range of experiences, expertise, and attitudes I have encountered have
stimulated my creativity and problem-solving abilities, which I believe will contribute to more innovative and robust research in the future. Overall, this research placement has been a transformative experience, reinforcing my passion for research and providing me with the inspiration and motivation to tackle complex scientific questions with renewed vigour and creativity.
Is there anything else you’d like to mention?
I would like to express my heartfelt gratitude to the entire EACR Travel Fellowships team and the evaluation Committee for their very positive consideration of my proposal. Your support has been essential in undertaking this journey and experiencing something that has greatly benefited my current scientific career. It has allowed me to catalyse my exposure as a researcher in a city as significant for biomedical cancer research as London. Thank you for giving me the opportunity to learn, contribute to such interesting projects, and share my working time in what I now consider my second home laboratory. I am confident that this experience will open doors and have a significant impact on my future academic development.
If you are interested in applying for the Travel Fellowship scheme, please click here for more information: EACR Travel Fellowships.