Interview with Amatta Mirandari

Amatta Mirandari is a third year iPhD student working with our colleagues Professor Jon Strefford, Dr Jane Gibson and Dr Helen Parker in the Cancer Genomics, studying a rare disease called Splenic Marginal Zone Lymphoma (SMZL). Amatta explains her research, why she chose to come to the University of Southampton and how she wants to develop cancer research activity in her home country of Indonesia.

What are you currently working on?

My work is currently focusing on analysing and understanding the epigenome of mature B-cell malignancies.

Together with colleagues in the Cancer Genomics group, we are specifically looking at a disease called Splenic Marginal Zone Lymphoma (SMZL), a rare, low-grade B-cell malignancy that comprises 2% of all lymphoid tumours.

Whilst often indolent in nature, a significant proportion of patients will develop progressive disease requiring treatment, some of which will undergo transformation into a diffuse large B-cell lymphoma with dismal survival.

Misdiagnosis of SMZL can also occur due to the lack of disease specific pathogenic features, rendering SMZL difficult to distinguish from other similar mature B-cell neoplasms. SMZL remains relatively understudied due to its rarity and the lack of availability of genome-wide data, the latter of which have only been generated from smaller cohorts with minimal matched tumour-germline information. Because of this, there is still a lack of development of accurate diagnostic and prognostic biomarkers.

However, we hope to improve on that!

We currently have access to one of the largest cohorts of SMZL patients with matched tumour-germline samples, thanks to our collaborations with researchers across Europe. Excitingly, we have access to whole genome sequencing (WGS) data of 35 paired tumour-normal samples – the only known dataset of its kind in SMZL!

Together with other sequencing technologies, we are working to piece together an understanding of the entire epigenomic landscape of this disease and develop insight into the mechanisms that is causing them to develop disease.

This project is funded by both my own PhD funding from the Centre for Cancer Immunology Talent Fund and by our involvement in the EARLY CANCER RESEARCH INITIATIVE NETWORK ON MBL (ECRIN-M3) consortium.

What impact could your research have on cancer patients?

Through my project, we hope to unmask the genetic lesions and alterations of these SMZL patients, which can hopefully be used to better inform their management and targeted treatments. Our findings could help to develop novel biomarkers that better help diagnose and further predict the disease course in cancer patients. This will enable better management which would be based on risk stratification and hopefully develop targeted treatments for precision medicine.  

Why did you decide to focus on that particular area of research?

DNA is the building block of life. Every single cellular process in our body is encoded by our genome, which acts as our genetic blueprint. To me, trying to understand the cancer genome is like trying to unravel a puzzle, with DNA sequences acting as puzzle pieces for us to probe, and I have always loved problem solving and puzzles!

My work is about understanding how different genomic mutations and lesions truly fit and work together to drive cancer development. Once we understand this, we get closer to completing the puzzle to finally seeing the full picture.

Why did you decide to work at Southampton?

I grew up in Jakarta, Indonesia until I was 17 and then I moved to the UK to pursue my undergraduate degree. Throughout my studies, I really took an interest in bioinformatics and genomic medicine which exposed to both the clinical and academic side of cancer research. The experience really cemented my love for cancer genomics, which is now the area of research of my PhD!

The amazing hub for cancer research, with clear opportunities for multi-disciplinary collaborations within the department and its links as well to many external collaborators, really attracted me to Southampton. Even during the application process, it was already clear how supportive the community is here, and that would be a place where I would be given the opportunities to really grow and develop my talents as a researcher. I was also very attracted to the iPhD course, which allowed me for a year to first try out different research areas before committing to a full PhD – through this scheme, I have managed to learn so many new skills, especially in the lab!

What is your long-term goal?

After completion of my PhD, my goal is to continue to work in academia for a few more years here in the UK to gain experience in the cancer research field. I hope to then go back to Indonesia, to help develop our cancer research there. While it has indeed improved along the years, Indonesia’s cancer research and development are still lagging in comparison to the UK. A lot of the technologies that are commonplace here are yet to be explored or developed back home. I hope to be able to bring my experience and expertise to help improve the quality of cancer research in Indonesia, with a new set of tools to apply to research back home.

What excites you most about the future of your research field?

The continuous and rapid development of technologies available! It seems that every few months, new methods and technologies would be released that help to solve the questions that we never could before, for a more thorough understanding of the disease we are studying.