Current Research on Endometriosis: An Interview with Abbey Lissaman

Endometriosis is a multifactorial disease, there are many contributing factors.

After the 15th “World Congress on Endometriosis” in Edinburgh, the psychologist of the Endo-App, Teresa Götz, met the New Zealand PhD student and endometriosis researcher Abbey Lissaman. Her PhD work at the University of Auckland focuses on epigenetic influences on hormone regulation during the menstrual cycle and their impact on endometriosis.

Teresa Götz: Could you first probably introduce yourself briefly?

Abbey Lissaman: My name is Abbey Lissaman. I am a second-year PhD student at the University of Auckland in New Zealand, and I’m studying the regulation of steroid hormone signaling in the endometrium and epigenetic mechanisms that might contribute to endometriosis.

Teresa Götz: How did you come to research endometriosis and specialize in epigenetic mechanisms?

Abbey Lissaman: I have always been interested in biomedical science. In my undergraduate degree, I did a major in biomedical science, and then I took as many papers as possible that included any reproductive biology. The field was very fascinating to me. I did a one-year honors research project at Auckland in the placental biology group, during which I did a research project with a lecturer whom I really admired on early placental development. Another lecturer that I really admired did work on endometriosis, endometrial biology, and the menstrual cycle. I found that really fascinating as well, so I decided to change topics for my PhD and that’s where I am now. My supervisor is Dr. Anna Ponnampalam and she is quite an experienced researcher in the endometrial field. I’ve got a fantastic team of supervisors.

Teresa Götz: What is your main motivation to do research in the field of endometriosis?

Abbey Lissaman: I describe my passion for this field as equally frustrating as exciting. It’s very exciting to be part of a field that has so many opportunities to get involved and there’s lots of research to be done. However, it is frustrating that so much of this research hasn’t been done already. We’re just so far behind in our understanding of how the uterus works, and our knowledge of female and reproductive biology. It’s frustrating when I come across things that in theory we should already know. I’m excited to be involved in that. I think the main motivation is just getting a better understanding of female biology because it has not received the amount of focus it deserves in previous decades.

Teresa Götz: In your opinion, what is the greatest challenge in endometriosis right now?

Abbey Lissaman: The greatest challenge is that endometriosis is a multifactorial disease, there are many contributing factors. My work is focusing on the epigenetic regulation, which is just one of many contributing factors. My lab group is focused on this one specific mechanism trying to figure out whether it plays a role at all. The uterus is a complex organ by nature, let alone in conditions like endometriosis. Now that it’s starting to get more attention in medical research and in the general public, the challenge is to put all of the work that’s being done worldwide together to try and get a greater understanding of it. It is a challenge to get everybody to collaborate, simply because there are so many different fields in this complex disease that people are focusing on. There is so much work to be done and so much exciting work that’s being done, but we don’t have the full picture yet.

Teresa Götz: Could you try to summarize your work for the patients?

Abbey Lissaman: Over the course of the menstrual cycle, there is a lot of different hormone signaling happening. The hormones estrogen, progesterone, and androgens, all signal through binding to their receptors. The expression of these receptors changes across different points of the menstrual cycle and in different cell types. Part of the way that expression is regulated is by epigenetic mechanisms, which are molecular changes that turn gene expression on and off. You can imagine at some points of the menstrual cycle it would be beneficial to have some genes turned on and other genes turned off, and at different points or in different cell types you have another gene that’s turned on or off. The uterus and the endometrium are very dynamic tissues, so we have those changes happening all the time. This regulation can go wrong sometimes, and you can imagine that will affect the signaling of estrogen and progesterone in the endometrium. My work is investigating the mechanisms of epigenetic regulation of steroid hormone signaling, how those genes are turned on and off, to get a better understanding of how the normal endometrium is regulated throughout the menstrual cycle. We hope to continue that research to discover how this regulation is different in endometriosis. That will help us better understand part of the way the endometriosis might develop. Further down the line, we might be able to target that mechanism for potential diagnostics or treatments.

Teresa Götz: Are there future research goals, like other projects coming up?

Abbey Lissaman: We have a lot of exciting work coming up. The ways that we can investigate this epigenetic regulation are quite complex. The methods are not fully optimized for the endometrium, because we don’t have a very good understanding of this regulation yet. In simple terms, there are two epigenetic markers that we are interested in. Methylation tends to be involved in gene silencing, so turning the gene expression off. Hydroxymethylation tends to be associated with gene activation, turning the gene expression on. The bit of work done in the endometrium tends to focus on methylation, whereas the work on hydroxymethylation is lacking. The methods that we use to measure these mechanisms are limited and have only picked up methylation and not hydroxymethylation. Because of their opposing effects, however, it’s very important for us to be able to distinguish between these two different regulatory mechanisms. We have been trialing different methods of treating DNA to be able to identify the amount of methylation or hydroxymethylation happening in a certain DNA sample. We’ve spent quite a bit of time optimizing them and understanding and interpreting that data. Hopefully, we will get some insightful data in the next six months or so. The methods that we’ve had up until this point have not been specific or informative enough. It is a huge challenge to figure out how to measure hydroxymethylation. Our previous work suggests that hydroxymethylation might be involved in the endometrium, so we are trying our best to be able to measure that. We treat the DNA that we isolate from endometrial tissue samples in a specific way that preserves this methylation or hydroxymethylation. You can think of a strand of DNA, and you can imagine little molecules sitting on the outside of it, which we can measure. Depending on if those are there or not, the gene is activated or turned off. We perhaps could interpret that there’s a lot of methylation happening in a particular gene, and that suggests that there’s more gene silencing happening so less hormone signaling. Or the opposite, there’s not much methylation happening or there’s a lot of hydroxymethylation happening and so there’s over-activation of the receptor which will lead to more signaling happening.

Teresa Götz: What do you think about the concept of digital self-help, as with the Endo-App?

Abbey Lissaman: I think it sounds fantastic. My background is scientific and not clinical, but I can see how a digital approach could help patients. It’d be a lot more interactive, and a good way for patients to find community. It is also a great way to communicate with patients and for them to be able to record symptoms and get a better-connected way of approaching endometriosis, because it’s very common, and we still don’t know a lot about it. A digital approach is a good way of collecting data from a scientific point of view, but also from a patient point of view. It’s good to feel heard and understood and have your needs attended to. Any digital health resources are good initiatives.

Teresa Götz: Is there anything else you would like to share with those affected by endometriosis?

Abbey Lissaman: It’s a complex disease and a complex problem that we’re trying to solve as scientists. Recently in New Zealand, we have news articles coming up about patient’s perspectives, their pathway to getting a diagnosis, and their experience, and we’re getting a lot more awareness. A lot more people are aware of the condition and aware of how patients are affected. I think not as many people are aware of what science is happening. The patients need to know that there is a lot of science happening and we are working at it. It would be great to be able to share more from both the scientists’ and clinicians’ perspective about the same problem.

Thank you so much for the opportunity to chat about my research! I’m really passionate about this work and I’m excited to see where the field goes.

Teresa Götz