“EACR Travel Fellowships are an invaluable opportunity” – Experiences from 5 EACR Travel Fellows

Home institute: Trinity College Dublin, Ireland
Host institute: Massachusetts Institute of Technology/Harvard Medical School, Boston, USA
Dates of visit: 24 June 2019 – 30 August 2019
Other funding organisations who supported your trip: The British Society of Immunology (BSI). During the first week of my visit, I presented my research at the Abcam “Immunometabolism: Fundamentals to Prospective New Therapies” conference that was held in the Joseph B Martin Conference Centre in Harvard Medical School. I received a travel grant from the BSI which covered the cost of the registration for the conferences and contributed to the costs of flights and accommodation.

Research: I am a PhD student under the supervision of Dr. Lydia Lynch in Trinity College, Dublin. It is now well established that obesity increases the risk of developing a number of different types of cancer, an association which is due in part to a defective anti-tumour immune response. My current research aims to understand the impact of weight loss on systemic metabolism and immune function in obesity. This knowledge will uncover specific metabolic pathways harnessed by weight loss to improve immune function in obesity, which may result in decreased tumour burden.

Can you summarise the research you did or what you learned on your visit?

The Lynch lab recently uncovered that impaired immuno-metabolic responses and thus defective anti-tumour immunity contributes to the increased risk of cancer in individuals with obesity. I am investigating if weight loss can reverse the immuno-metabolic defects observed in obesity. Prior to my visit, I shipped tissues, PBMCs and blood plasma from obese mice and individuals with obesity that have lost weight to Harvard Medical School.

In collaboration with Dr. Evanna Mills, a postdoctoral researcher in Dr. Ed Chouchani’s lab in the Dana Farber Cancer Institute in Harvard Medical School, we performed targeted metabolomic analysis of blood plasma. The goal of this experiment was to investigate whether the plasma metabolome is altered in obesity and if weight loss can influence the availability of particular metabolites.

I am very lucky

In addition, I performed single cell sequencing experiments in the Single Cell Genomics Core. This was directed by Professor Michael Brenner from the Brigham and Women’s Hospital, Harvard Medical School. Using this data we are uncovering how obesity alters the transcriptome of the immune compartment of metabolic organs and if weight loss has an effect on gene expression.

Describe a typical day on your visit

Like any research scientist, my days oscillated between data analysis and performing experiments.

I learnt how to use the online tool “MetaboAnalyst” to analyse the metabolomics data that we collected on blood plasma. Using this tool I could make PCA plots, heatmaps and volcano plots which informed me about how the metabolome is altered between lean and obese mice and the changes that occur after weight loss. I could then pick out those metabolites that are significantly changed between groups with 95% confidence. This was my first time analysing a big data set and I’m sure the skills I’ve learnt from this will be very useful in my hopefully long-lasting research career.

My wet lab work consisted of FACs sorting particular immune populations from the adipose tissue and liver of mice, and PBMCs from humans with obesity and following weight loss. Single cells were then incorporated into an oil droplet with a bead (GEM – gel bead in emulsion) so that the mRNA from each cell can be barcoded to identify the cell of origin of that particular transcript. In collaboration with bioinformaticians from the CSAIL institute in MIT I learnt how to analyse this data using the software R.

this prestigious travel grant has already opened many doors for me

What were you able to do that you could not have achieved in your home lab?

Single Cell Transcriptomics is a relatively recent technology that is used by researchers publishing in many high impact journals. I travelled to Boston to perform such experiments because I would not be able to do so in Ireland. We chose to work with the 10x Genomics Core that was established by Professor Michael Brenner in Brigham and Women’s Hospital as the technicians are experts in every aspect of this technology.

In addition, we are collaborating with Professor Manolis Kellis from MIT on this project. Travelling to Boston this summer meant that I got the opportunity to meet with bioinformaticians from the Kellis lab. I learnt how to write the necessary codes to integrate, process, normalise and analyse the single cell sequencing data using the R software. We used the Seurate package that is commonly used for this type of analysis. I am grateful for those that shared the Seurate Master Vignette with me and took the time to teach me how to perform this type of analysis.

Have you brought back any specific technique that has benefited your home lab?

Thanks to the EACR travel grant I had the unique opportunity to perform single cell sequencing experiments. In addition, I was taught by expert bioiformaticians how to write basic codes to aid me in the analysis of these datasets. My home institution recently received funding from Science Foundation Ireland to establish a next generation flow cytometry and single cell gene analysis core – the first of its kind in Ireland. Using the wet lab and computational skills that I have learnt this summer I will be able use this core for my future experiments. In addition, I will be able to establish this new technique in the Lynch lab. This will enable my colleagues to make use of this cutting-edge infrastructure.

How has this visit been beneficial to your research and your career?

Securing this prestigious travel grant has already opened many doors for me and will undoubtedly enhance my future prospects as a scientist. I got the opportunity to use a cutting edge technology which will certainly strengthen the impact of future publications. This dataset will be available to other current and future members of the Lynch lab and will hopefully give rise to many publications.

This past summer I broadened my scientific network and interacted with leading researchers in prestigious institutions like Harvard Medical School and the Computer Science and Artificial Intelligence Laboratory located in MIT. Collaboration is essential for a fruitful research career. This visit gave me the confidence to talk to members of other international labs about our work and recent publications in the field. I am very lucky to have secured this independent funding to carry out part of my PhD research in the United States, a visit that will certainly stand out when I am applying for funding for a post-doctoral research position.

Did you take part in any interesting local activities?

Boston is a booming city full of history which ensured that I wasn’t short of tours and activities during the summer. To become more familiar with the city I first took part in guided tours including the Duck Tour and the Freedom Trail. I visited the Science Museum in Cambridge where there was an exhibition on the first moon landing – Apollo 11. It was only then did I realise that the date was the 26^th of July 2019 – exactly 50 years after the first landing on the moon.

I went to a Baseball Game in Fenway Park one evening (Go Red Sox!). I had never been to a Baseball game before, nor was I familiar with the rules of play. Thankfully one person we went with was an avid Red Sox fan so I was a pro by the end!

As I was in Boston for a whole summer I decided to immerse myself in American culture and joined a Flag Football League. I was part of the “TDs” (short for Touch Downs) team and we played in Brigg’s Field in MIT every Sunday afternoon. At first I must admit that I was very bad! I’m used to rugby (with Ireland being the number one team in the world) so having the Quarterback throw the ball forward was very alien to me! But I got to understand the rules and had the time of my life. I’ve made life-long friends who I am still in contact with.

Home institute: Technion Institute of Technology, Israel
Host institute: Harvard Medical School, USA
Dates of visit: 4 August 2019 – 12 October 2019
Other funding organisations who supported your trip: Technion International

Research: Glioblastoma is a devastating incurable disease with median overall survival of about 15 months, under maximal frontline therapy. This can be greatly explained by the presence of the blood brain barrier (BBB) that prevent the penetration of drugs into the brain and a highly immunosuppressive tumor microenvironment that inhibits any immune response. Daniel’s research investigate potential mechanisms for overcoming these two hurdles at once. Here we develop a novel therapy combining focused ultrasound and immunotherapy aiming to train and to activate of the host’s immune system to recognize the tumor and lead to its abrogation.

Can you summarize the research you did or what you learned on your visit?

During my visit I participated in multiple activities together with my lab colleagues. Since one of the main objectives of the trip was to gain knowledge about the synthesis of drug delivery systems, I followed and gained knowledge with the daily work practice of my colleagues. These included the synthetization different types of nanoparticles and how to perform their conjugation to special moieties. Additionally, I learned about the fabrication and handling of the lab specially developed hydrogels that can be filled with drugs and implanted locally on tumors.

In addition, since the lab was also submitting its candidacy for a series of grants I was happy to be in constant contact with my advisor and her post-docs observing the realization of multiple experiments and learning how to write grants.

Describe a typical day on your visit.

After getting to the lab every morning, I use to join one of the lab groups during their morning briefing. There we would decide the next experiments we would perform in the day/upcoming days. I was always following the work of postdoc students which were developing novel formulations of nanoparticles. Since the experiments were time-consuming, I spent lots of time observing and learning how to perform them at the lab benches.

Once a week me and Prof. Natalie would meet to check the progress and solve any possible doubt that arose regarding the experiments I had been following. She was always very available and willing to help.

What were you able to do that you could not have achieved in your home lab?

My home lab is focused in the development of medical imaging systems (Prof. Haim Azhari’s Lab). For this reason, the lab is not equipped with the tools necessary to synthesize nanoparticles or molecules in general. Our research is very well defined in a sense that each lab is developing its specialty: Medical Imaging Lab focuses on development of the focused ultrasound system while at the artzi’s lab we develop the drug delivery systems.

Did you have a personal mentor or anyone who particularly helped you?

Prof. Natalie Artzi was very important during this period. Prof. Natalie is a leading scientist in the field of drug delivery systems and she is a very busy person having to manage the lab itself, her family and the startup she founded (BioDevek).Even with all the daily tasks and the very limited time available, Prof. Artzi always available to guide and mentor me. I felt that she can see much further than the experiment itself. She always directed me towards the big picture of the project.

This visit was extremely beneficial

Additionally, the members of her lab were essential for helping me as well. Especially the post-docs (Shiran Farber, Pere Dosta Pons, Santosh Kalash, Mian Wang).

How has the trip inspired you in your research?

Multiple aspects of the trip inspired me in my research. First I would point out that getting in contact with a lot of different projects simultaneously helped to open my mind about my own project. This include, for example, the possibility of using new types of particles for my research.

Additionally, watching and helping in the building of research grants taught me to work hard until the last minute and don’t give up even if the experiment didn’t succeed in the first times we ran it.

I thought it was very interesting in a management perspective to see that the lab colleagues always have lunch together. Although it seems minor, I can that it can really have a positive impact in the work environment.

Have you brought back any specific technique that has benefitted your home lab?

I learned how to synthesize nanoparticles and conjugating them with specific moieties. This is a skill that is extremely necessary for my research continuation at my home lab. This will be further coupled with the ultrasound system we developed at the Technion and then tested in-vivo.

How has this visit been beneficial to your research and your career?

This visit was extremely beneficial. Apart of the aspects described above, I believe that several factors have/will have a positive impact in my career.  Some of these factors I would point out are being in contact with a completely different laboratory that focused in a new field of research (for me) and located in a very prestigious university (Harvard), getting to know very hard-working and very collaborative students (at Artzi’s Lab) and finally learning from the basics until an intermediary level (so far) about the fabrication processes of drug delivery systems.

As my research is extremely collaborative in essence, this trip helped to implement this concept in reality expanding horizons and possibilities of how to best implement the solution we propose for brain tumors.

Home institute: Laboratory Experimental Haematology (LEH), University of Antwerp, Belgium
Host institute: Laboratory of Cancer Immunotherapy, University of Osaka, Japan
Dates of visit: 3 May 2019 – 7 July 2019
Other funding organisations who supported your trip: Research Fund of the University of Antwerp

Research: T lymphocytes cells are a type of cell in our immune system that can recognize and eliminate cancer cells. To do this, they express T-cell receptors (TCRs) that bind to peptides presented by cancer cells. Unfortunately, the number of cancer-specific T cells is usually very low. My research project focuses on modifying T cells with cancer-specific TCRs and on novel strategies to improve the functionality of the engineered T cells. The main objective is to redirect and boost their anti-tumor capacity towards cancer cells in an effort to further advance adoptive T-cell immunotherapies for cancer.

Why did you decide to apply for an EACR Travel Fellowship?

As part of my doctoral studies, I wanted to learn an essential technique for my project: how to isolate and clone T-cell receptors that can recognize tumor antigens. The best option to do this was to travel to our collaborators’ laboratory in Japan. They have extensive experience in this topic. The possibility of learning new techniques and about other working environments was very appealing to me. The uncomplicated and approachable nature of a highly regarded association such as the EACR encouraged me to apply.

Why did you choose the host lab?

I chose Professor Yusuke Oji’s group because of the international relevance in my field of study and the long-standing collaboration between our laboratories. The partnership began several years ago by Prof. Zwi Berneman (head of LEH) and Prof. Haruo Sugiyama, former leader of the Japanese group. Professor Sugiyama is a pioneering researcher in the biology and the use of Wilms’ tumor 1 protein as a cancer vaccine, protein that he discovered in 1992. Moreover, the University of Osaka is one of the best universities in Japan. Therefore, this was a very attractive opportunity to further enhance our collaboration and to learn different techniques in an outstanding environment.

Can you summarise in the research you did or what you learned on your visit?

it was a very fulfilling experience

The research visit focused on the generation of allogeneic and high-avidity T-cell receptors (TCRs) specific for tumor antigens using HLA-mismatched donors. In particular, I learned how to isolate TCRs from T-cell clones that are reactive towards tumor cells that express WT1 epitopes. The TCR sequences were analyzed and cloned into vectors for the posterior sub-cloning into plasmid vectors suitable for the in vitro transcription of messenger RNA (mRNA). These mRNAs contained the sequences of the TCR alpha and beta chains for the engineering of T cells in my lab at the University of Antwerp.

Describe a ‘typical’ day on your visit

A typical day in the lab started at 9am. I would discuss the plans for the day with Professor Fumihiro Fujiki, my supervisor. In general, the experiments involved running plenty of PCRs, preparing gel electrophoreses, plasmid amplifications and isolations. As well as this, I analysed samples by flow cytometry and cultured different types of cells. Usually, we stopped for lunch at 1pm. Lunch breaks were my favourite part of the day because I had the chance to speak with different members of the lab about differences between Japanese and European cultures, work ethic or languages. Usually, the day finished at 8 or 9pm.

Did you take part in any interesting cultural activities?

I was lucky to be part of exciting cultural activities with the members of the host lab and other international researchers that I met at the University of Osaka. On the first days of my stay, they offered me a welcome dinner with the different members of the group in a typical izakaya and traditional kaiseki. They explained the particularities of Japanese cultures and the particularities of each dish.

Other activities included trips to Nara and Osaka with Dr Morimoto and her students. Nara is a beautiful city that was the ancient capital of Japan many centuries ago. They showed the best spots in Nara and typical dishes in Osaka. We also visited the Museum of Housing and Living, a museum dedicated to life in Osaka during the Edo period. To finish my stay, they indulged me with another group dinner and farewell cards.

this research visit will boost my career prospects

What was a personal highlight of your trip?

The Japanese culture amazed me. The host group was so welcoming. They made sure that I had all the necessary information needed to make my stay comfortable. It was also very enlightening to learn first-hand about a broad range of molecular and cellular techniques. On both a professional and personal level, it was a very fulfilling experience.

Did you have a personal mentor or anyone who particularly helped you?

Professor Fumihiro Fujiki was my primary supervisor for the research stay. Dr Soyoko Morimoto was the go-to person when Professor Fujiki was not available. They mentored me and guided me through all the protocols and techniques that I used in their laboratory. Both are excellent researchers and made sure that I learned from their vast knowledge of molecular and cellular biology. I could not have asked for better mentors!

How has this visit been beneficial to your research and your career?

This experience has allowed me to learn many techniques that are essential to my field of study. In this particular case, we focused on the isolation of high-avidity TCRs that recognize epitopes of the Wilms’ tumor 1 protein, a tumor-associated antigen found in many hematological malignancies. The know-how I obtained during the research stay will be vital for the completion of my doctoral project. Moreover, I can apply the techniques and protocols that I learned to other antigens and malignancies. This will allow me to open additional lines of research in the future. Adoptive transfer of engineered T cells with cancer-specific receptors is currently one of the most promising cancer immunotherapies. Therefore, this research visit will boost my career prospects after obtaining my doctoral degree.

Is there anything else you’d like to mention?

I encourage all Ph.D. students to go on an international research visit. It will be a fantastic experience that will boost your doctoral project and career prospects and will help you grow on a professional and personal level. The EACR Travel Fellowships are an invaluable opportunity to support your visit.

Home institute: Institute for Cancer and Genomic Sciences, University of Birmingham, UK
Host institute: Leiden University Medical Center, The Netherlands
Dates of visit: 1 – 15 July 2019

Research: Half of all patients diagnosed with rectal cancer have locally advanced disease. Prior to surgery, these patients are treated with a combinaton of chemotherapy and radiotherapy (nCRT). However, only 2 out of 10 patients undergoing this treatment combination will have tumour remission. My research goal is to clarify the biological mechanisms underlying this response variability. This will enable pre-treatment identification of patients that will benefit from nCRT and the discovery of novel therapeutic options for patients that do not respond to this treatment. To achieve this I am investigating the cancer genome and the surrounding tumor microenvironment of nCRT-sensitive and nCRT-resistant rectal tumours; I am also using rectal cancer patient-derived organoids – mini-tumours grown in the lab –  as a model to discover drugs that can improve tumour sensitivity to radiation.

Why did you choose the host lab?

The LUMC was one the first institutes to have the Hyperion system for Imaging Mass Cytometry, a novel technology that I wanted to use to gain new insights on how tumour immunology can modulate rectal cancer response to nCRT. Furthermore, the lab has expertise using this technology to perform deep immunophenotyping in colorectal tumours. I contacted the host lab principal investigator – Dr. Noel de Miranda – and we discussed a research proposal I was planning to submit to CRUK Birmingham Centre Development Funding. He was very supportive of the idea. Fortunately I secured the funding, so then the next step was to obtain a travel fellowship.

it has helped me build a research network which will greatly contribute to my career

Why did you decide to apply for an EACR Travel Fellowship?

Being an EACR member has for long had a positive impact on my research path. It facilitated networking within the European cancer research community and beyond, and allowed me to present my work to a broad audience. So for me it applying for an EACR Travel Fellowship was a natural first option.

Can you summarise the research you did or what you learned on your visit?

The goal of my visit to the Immunogenomics lab was to perform a comprehensive immunophenotyping of nCRT-sensitive and nCRT-resistant rectal tumours using Imaging Mass Cytometry. The host lab has vast expertise in this state-of-the-art technology that enables high-multiplexed in-situ protein detection while preserving the tissue morphology. My two-week stay was an intensive training that covered all the steps from antibody labelling, to running the samples on Hyperion system and image processing for further analysis.

Did you have a personal mentor or anyone who particularly helped you?

I had constant support from Marieke Ijsselsteijn – a final-year PhD student. She showed me around the lab facilities and walked me through the training, from sample preparation to image processing.  Moreover, Dr Noel de Miranda’s door was always open to discuss the training progress and the subsequent data analysis.

Describe a typical day on your visit.

My day started with a 10 minute walk to the lab through Leiden’s picturesque canals. I would prioritize the planned wet lab tasks and use any spare time (e.g. incubation times) to get the hang of the software tools required for image processing. I felt fully integrated in the lab: attended the lab meetings, joined the group lunches. It was a great opportunity to get to know the lab members and their research interests.  On top of this I also attended the weekly LUMC organized talks given by invited international speakers. There was never idle time!

Does your lab plan to do any future collaboration/publication etc with the host lab?

This research travel initiated a collaboration between the two labs. The results obtained from this research visit will integrate a joint publication. Furthermore, future collaborations on common interest topics are open to discussion.

Did you take part in any interesting local activities?

I had the opportunity to explore Leiden’s landmarks over the weekend. I particularly enjoyed tasting the traditional food at the local market held every Saturday next to the canal. Also, I visited Amsterdam, which was just 30 minutes away by train. It was great to stroll by the iconic historic districts, and absorb the culture the city has to offer.

How was this visit been beneficial to your research and/or your career?

The EACR Travel Funding contributed to my personal development allowing me to learn  cutting-edge methodology and use it to obtain valuable insights to my research. Furthermore, it has helped me build a research network which will greatly contribute to my career. I am thus very grateful to EACR for funding my research visit.

Home institute: Department of Pediatric Hematology and Oncology, Justus-Liebig University, Giessen, Germany
Host institute: Department of Pathology, Boston Children’s Hospital, Harvard Medical School, USA
Dates of visit: 1 April 2019 – 31 August 2019
Other funding organisations who supported your trip: Marie Skłodowska-Curie PhD Fellowship “ALKATRAS”

Research: I work on an aggressive blood cancer called Anaplastic Large Cell Lymphoma (ALCL) which mainly affects children and young adults. This type of cancer is characterized by a chromosomal translocation which leads to the expression of the oncogenic NPM-ALK fusion protein. My main research focus is to understand how the immune system recognizes and potentially eliminates lymphoma cells harboring this mutation to translate this knowledge into the development of a cancer-specific immunotherapy.

Why did you decide to apply for an EACR Travel Fellowship?

I first learned about the fellowship when I became an EACR member at the beginning of my Ph.D. I decided to apply when the opportunity came up to visit Dr. Roberto Chiarle’s laboratory in Boston. The EACR Travel Fellowship was an essential support to realize my internship at Boston Children’s Hospital.

Why/how did you choose the host lab?

I got to know Dr Roberto Chiarle through my Marie-Skłodowska-Curie Ph.D. program. It is embedded into a network of research groups working on ALK-related malignancies. My project is focused on the interplay between CD4 T cells and lymphoma cells which express the oncogene ALK. Dr. Roberto Chiarle’s lab investigates therapeutic approaches to target ALK, including ALK-specific immunotherapy. Therefore, we started a collaboration based on our same research interest to investigate the role of CD4 T cells in this context.

Can you summarize the research you did or what you learned on your visit?

The main objectives of the project were to test and validate the efficacy of ALK-derived peptides, which are potentially involved in the anti-ALK CD4 T cell response in patients, in a vaccination study in mice. Another aim is to gain insight into the role of CD4 T cells in protective anti-ALK immunity. I have learned how to design, perform and analyze experiments in mice. Also, I broadened my knowledge in cancer immunology, and I learned new immunological techniques which I will apply in my further research. I was exposed to a highly productive, multicultural and inspiring scientific environment. It was an amazing opportunity to collaborate with another research group at Boston Children’s Hospital.

Describe a typical day on your visit.

I lived not far from the Longwood Medical Area, where the Boston Children’s Hospital is located. My daily route included a walk along the impressive Harvard Medical School building with its beautiful garden. It was an exciting experience to be surrounded by world top research institutes and companies. My work in the lab was very diverse and included working in cell culture, designing and preparing cancer vaccines, performing experiments in mouse models, and analyzing samples by flow cytometry. My guide was Dr Rafael Blasco-Patiño, with whom I planned my experiments and discussed results. When possible, all lab members shared lunchtimes, where we discussed science. Occasionally, we would also go out for an after-work beer. Besides my daily routine in the lab, I attended regular lab meetings and seminars. I also had the extraordinary opportunity to meet leading scientists at symposiums.

What were you able to do that you could not have achieved in your home lab?

At my home institution, I primarily worked with human samples, which I analyzed for an ALK-specific immune response in vitro. At a certain point, it was necessary to translate and validate my findings into in vivo mouse models. This is not possible at my home institution.

I would like to thank the EACR for selecting me for this fellowship which allowed me to make this invaluable experience abroad.