Alexander Azizi is an Academic Clinical Fellow at the Cancer Research UK Cambridge Institute in the UK who received an EACR Travel Fellowship to visit and work at the Broad Institute of Harvard and MIT in the US between September and December 2023.
The EACR is supported by Worldwide Cancer Research to provide Travel Fellowships of up to €3,500 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: Alexander Azizi
Job title: PhD student
Home institute: Cancer Research UK Cambridge Institute, UK
Host institute: The Broad Institute of Harvard and MIT, US
Dates of visit: September – December 2023
Other funding organisations who supported your trip: National Institute for Health Research
Research: Immunotherapy effectively treats advanced lung cancer by activating the patient’s immune system to shrink tumours. However, it is effective for different reasons for different people and it is not effective for everyone. The reasons for this variation in responses are not fully understood. My host group recently analysed tumours from nearly 400 lung cancers before immunotherapy, detailing the mutated DNA and biological changes. My project was a closer examination of this data to identify new reasons for patient responses and to create a mathematical model to predict which patients are likely to respond well to immunotherapy for lung cancer.
How did you choose the host lab?
Professor Getz has been instrumental in developing and analysing numerous large-scale cancer genome projects including The Cancer Genome Atlas (TCGA) and as part of the International Cancer Genome Consortium (ICGC). I had previously discussed PhD opportunities with Professor Getz and knew that his group at the Broad Institute is interested in predictive biomarkers and cancer subgroups. Earlier this year, the group published an initial analysis of a cohort of patients with advanced non-small cell lung cancer treated with immunotherapy. They had conducted bulk whole exome sequencing and whole transcriptome RNA sequencing, relating their molecular subtypes to clinical outcomes. I believed that the dataset was suitable for further analysis and was excited to contribute.
Can you summarise the research you did and what you learned on your visit?
My computational biology project aimed to further analyse the Stand Up to Cancer – Mark Foundation advanced non-small cell lung cancer cohort. The research outcomes were: 1) searching for new and impactful predictive biomarkers; and 2) creating an integrated classifier to predict responders to therapy.
1. We used multivariable logistic regression to associate damaging mutations in members of the interferon gamma pathway with response to immunotherapy. We are testing the robustness of this association with permutation based methods. Biological validation and testing in external cohorts are under discussion.
2. We created an ensemble machine learning model predicting responders in an internal validation cohort with an AUC of 0.80. Refinement is ongoing and will test this in an external, unseen cohort.
Describe a typical day on your visit.
I was given a desk and computer in the Getz Lab area at the Broad Institute, attending in-person each day. This facilitated participation in Cancer Programme meetings, Getz lab meetings, and educational sessions. It also enabled easy interaction with supervisors and lab members. A typical day might start with a Cancer Programme meeting, followed by scripting and data visualization in the morning, informal discussions with colleagues, and afternoon meetings with my supervisor, Dr. Ravi, and further analysis in the evening.
Did you take part in any interesting local activities?
One highlight was being invited to Thanksgiving by my friends in the lab. We had a roast ham and played games into the night. I spent an afternoon in baseball batting cages, went whale-watching off the Massachusetts coast, attended a Harvard football game, and visited Salem on Halloween weekend. As a lab, we attended the Boston Festival of Genomics, which was an interesting day of scientific exploration, drawing caricatures (photo attached) and a good chance to get to know the lab members.
Did you have a personal mentor or anyone who particularly helped you?
I am immensely grateful to Dr. Arvind Ravi, the first author on the initial SU2C-Mark Foundation Lung analysis and a post-doc (and MD/PhD) in the lab. He generously gave me lots of his time and guidance. He has a vast knowledge of different analytical techniques to understand both the biology and computational elements of the data. He, like Professor Getz, is also very kind and made me feel very welcome.
Does your lab plan to do any future collaboration with the host lab?
We plan to collaborate further to turn the current prototypes and abstract into two manuscripts. We have also involved collaborators across the US to support us with additional cohorts for biological validation and classifier testing.
How has this visit been beneficial to your research and career?
In the first instance, we have submitted an abstract to the American Association for Cancer Research (AACR) Annual Meeting and that has been accepted. This should build on my current knowledge from the European Association for Cancer Research (EACR) conferences and allow me to develop the further collaborations to bolster our initial findings. I have been invited back to the Getz lab and was able to interact with multiple clinical consultants across the US. My time with the lab has already widened my community significantly and has taught me a great deal about the statistical rigour of analysing large dataset. I would like to thank the EACR Travel Fellowship team for facilitating that.
If you are interested in applying for the Travel Fellowship scheme, please click here for more information: EACR Travel Fellowships.