Meet the first author: Anja Heß
Anja Heß is the first author of a recent study by the Meissner and Vallier Labs in Genome Biology. We talked with her about what drew her to the work, the one skill she learned during this work that she didn't expect to need, and the invisible work that went into the study.
Anja, could you briefly summarize your findings?
In this paper, we have developed a technology that allows us to use cell-free DNA that we take from cell culture medium to trace the maturity of cells or 3D models developing in a dish.
What problem or question did you try to solve, and what was your starting point?
Our work aims to differentiate stem cells into more mature cells that resemble human cells. These cells may eventually serve as model systems for human diseases or stem cell-based therapies. However, to determine whether this mature state has actually been reached, we must destroy the sample to access the genomic information, such as the DNA methylation state. We lose many cells during the process and introduce variation. This also means that we cannot trace a single cell population over time. In my work, we aimed to overcome this problem.
Why did you decide to pick this up on a personal level? What sparked your interest in this field?
I worked with organoids and more complex 3D systems for a while, and my dream was to be able to study the molecular features of cells without interfering with their growth or structure. I've heard about liquid biopsies in clinical settings, and they just seemed like the missing link to achieving that goal.
In what ways will other scientists benefit from your findings? What questions will they be able to answer?
I think the strongest benefit will be for scientists working with very precious samples, for example, organoids in a culture for a prolonged period of time. There are organoid types that grow for weeks, months, or sometimes even years. Having the ability to take a small amount of the medium to learn about the sample while letting it grow is a great benefit if you have such a precious models or specimens.
Are there any other practical implications?
We would be interested to explore how to use this technology for actual cell products. In cancer immunotherapy, one approach is based on CAR-T cells. Here, patients donate their own T cells, which are genetically modified in the lab and then used again to treat the patient's cancer. Could we predict the success of CAR-T cell therapy based on the cell culture before transplantation? If so, it would be very valuable and could serve as a blueprint for the quality control of other cell products.
Was there a skill that you learned during this work that you didn't expect to need?
I definitely learned patience because we repeated similar cfDNA monitoring experiments in different cell systems, such as stem cells, extraembryonic endoderm, and liver cells. Of course, it's not as exciting as when you do if for the first time but it was important for validation.
The final publication often only shows a small fraction of the work that went into a paper. Is there a part of your work that you wish was more visible in the final paper?
I started not only to follow the natural maturation of the hepatocytes in vitro but also to perform treatments, read out some effects in the cell-free DNA, and examine calcium signaling. This was great because it felt more functional. I think this will probably be explored more in the future.
What about you? What direction are you going in with your career?
Personally, I think I will move toward immune therapies or host immune interactions, though I haven't decided yet. However, I could definitely see myself working with this technology in the future. The goal of the paper was in the end to create a universal tool that can be applied to many different scenarios.
