Eleni Papachristoforou on therapeutic targets for human liver fibrosis

She is MRC DTP precision medicine PhD student at the Centre for Inflammation Research. Her research focuses on macrophage heterogeneity and single cell transcriptomics in liver fibrosis disease.

She also has an undergraduate and a postgraduate degree in Medical Sciences and Bioinformatics. During her undergraduate studies, she conducted research with Dr. Steve Jenkins on acute liver disease by analysing the effects of therapeutic administration of interleukin-4 (IL -4) on hepatocyte proliferation. Similarly, she conducted research in the field of regenerative medicine by working with Dr. Abdenour Soufi to investigate the transcriptomic and epigenetic changes of reprogrammed mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) and totipotent stem cells (iTSCs) by inducing different combinations of transcription factors (TFs).

Could you briefly summarise your work?

I am currently working on single cell transcriptome data analysis to define therapeutic targets for human liver fibrosis. Liver macrophages are important regulators of fibrosis and represent an attractive therapeutic target. However, macrophages are multifunctional and heterogeneous, implying that precise definition of pathogenic subpopulations is required to enable specific targeting. Macrophages in rodent models of liver fibrosis reflect several features of macrophages identified in human liver disease. However, the exact relationships between rodent models and human liver disease have not yet been defined. Recent studies using single-cell RNA sequencing (scRNAseq) have defined the pathogenic macrophages in human liver fibrosis. To define and test strategies to modulate these macrophages in vivo, in this study we aim to identify corollary macrophages in a relevant preclinical liver fibrosis model. By obtaining data from murine models of liver fibrosis (i.e., carbon tetrachloride, bile duct ligation, nutritional models) that include concurrent scRNA-seq, we will resolve fibrogenic macrophage subpopulations. We will proceed to map the transcriptomes of these cells to those identified in human cirrhotic liver tissue using state-of-the-art computational approaches. This will facilitate the identification of corollary populations and "core" signalling pathways that regulate liver fibrosis in different species and define tractable therapeutic targets for liver fibrosis.

Why is your research important? How is it relevant to people's lives?

Chronic liver disease (CLD) affects 844 million people worldwide, with over 2 million deaths per year. Regardless of the cause of liver disease, patients experience scarring of the liver or fibrosis. The degree of fibrosis predicts adverse clinical outcomes, but there are currently no effective antifibrotic therapies. Thus, there is a real interest in better understanding the biology of fibrosis in order to develop new treatments.

What are the major challenges in your field?

1. Handling sparsity in single-cell RNA sequencing
2. Defining flexible statistical frameworks for discovering complex differential patterns in gene expression
3. Mapping single cells to a reference atlas and cross-species integration analysis

What inspired you to be a scientist?

I do not think it was one thing that inspired me. It took me a long time to decide, but I think I realised at a young age that I like to do scientific work - that is, analyse and question things and look at problems in an organised, logical way. Now that I am a scientist, I am inspired by the fact that I can use my knowledge to solve biological problems related to human disease and be part of a team interested in developing potential therapeutic strategies for patients.

What do you like best about your job? What do you like the least?

Collaboration!!! I find it fascinating to talk and share ideas and knowledge with other scientists in the field and people who have a passion for research.

However, as a scientist, careers are very uncertain, which scares me.

If you could have tea with another scientist (alive or dead), who would it be? What would you talk about?

I would love to have tea with Sophia Louisa Jex-Blake, an outstanding pioneer who fought hard for women's rights in medicine in the 1870s along with six other women known as the Edinburgh Seven. I think it would be interesting to discuss how difficult it was for women to practise medicine and how it was for women to fight for their rights, and compare those years with today.

What is the most unusual thing you have done as a scientist?

Walking into a room forgetting what I wanted to do or get from there. This is such a common symptom of the brain being overloaded, and someone can call it the "doorway effect".

If you weren’t a scientist, what would you be doing?

I would be a photographer! I love being outside and taking beautiful pictures of landscapes and nature, so this seems like a good option.

Do you have any advice for people who want to go into this field of research or start a career as a scientist?

If you decide to pursue a career as a scientist, do not base your decision solely on whether the lab you apply to has a grant for you or routinely publishes in top-impact journals. Choose a place where you feel motivated and where you know fascinating things are being done. Just as important, try to pursue other professional activities, such as teaching, attending seminars, organising symposia, and engaging in public relations.

What do you think are the major challenges facing humanity? How can science help?

Global climate change and the need to urgently achieve sustainable development are the greatest challenges. I personally believe that we should create an environmentally friendly working environment in laboratories, promote recycling and try to minimise the use of plastic. This activity should also be considered by biotech companies, as they are the main suppliers of our reagents and consumables.

Related Links

Eleni Papachristoforou profile