Current Research on Endometriosis: An Interview with Dr. Ayse Nihan Kilinc
“I think the biggest collaboration is with the patients. I’m thankful to them that they are actually donating their tissues to us. We should be always thankful to them because they contribute a lot to our research.”
Teresa Götz: Could you please introduce yourself briefly?
Dr. Ayse Nihan Kilinc: I was born and raised in Turkey, and I received my undergraduate degree in molecular biology and genetics at Bilkent University in Turkey. I did my master’s at Yeditepe University in bioengineering. Then, I moved to Switzerland to do my PhD at University of Basel in the lab of Gerhard Cristofori.
In my PhD, I worked on cancer cell invasion and metastasis in breast cancer. Next, I moved to the United States to Princeton University and worked as a postdoctoral researcher in the lab of Celeste Nelson. There, I worked on how the tumor microenvironment affects cancer cell migration. Now,
I’m a postdoctoral researcher in MIT in Linda Griffith’s group and working on endometriosis and focusing on endometrial epithelial cell invasion and how the tissue microenvironment affects endometriosis.
Teresa Götz: How did you come to research endometriosis?
Dr. Ayse Nihan Kilinc: Actually, it is very interesting because I have always worked on cancer, especially on breast cancer, and I was always interested in women’s health and tried to work on women’s health research and started with breast cancer. I now moved to endometriosis because endometriosis and breast cancer have some similarities as well as differences.
In breast cancer epithelial cells, stationary epithelial cells can gain migratory and invasive properties. They can migrate to the other organs. In endometriosis, endometrial-like tissues can be present at different organs. But we still do not know how these tissues end up there and whether these cells have invasive capacity.
About Dr. Ayse Nihan Kilinc
Dr. Ayse Nihan Kilinc is a cell biologist specialized in endometriosis, uterine biology, and cancer research. Her expertise lies in advancing disease model development through sophisticated human 3D organoid models and microfluidic devices. Currently she is working with an interdisciplinary team at the Massachusetts Institute of Technology (MIT).
Also, I was always really fascinated and still resonate with this cell migration and the extracellular matrix which surrounds the cells. In humans and in animals, the cells are not floating they are within a spatial microenvironment. In disease progression, this microenvironment can affect the origination and the progression of the disease.
I used to work on cell invasion in a breast cancer setting and now I am working on endometriosis and apply my expertise in cell invasion. I was interested in switching to endometriosis field because it is particularly important and understudied area of women’s health. Tissue microenvironment affects breast cancer progression.
For example, during breast cancer progression extracellular matrix becomes stiffer. This actually helps to diagnose because it’s stiff tissue and it’s palpable. But tissue stiffening also affects the invasion and metastasis of these cells to the other organs.
In endometriosis and adenomyosis, endometrial-like cells can have the ability to grow into the muscle tissue, which is a stiffer tissue, and also fibrosis is often observed in some types of endometriotic lesions, which also again brings this stiff environment to the cells. Cells can sense their microenvironment, respond, and progress according to the environment.
Teresa Götz: In your opinion, what is the greatest challenge in the field of endometriosis now? Is it the lack of knowledge?
Dr. Ayse Nihan Kilinc: I think, yes. In particular, we still don’t fully understand how the disease originates actually, and how it progresses. Because mostly we depend on just the snapshots from the surgical specimens which is the endpoint.
That’s why we don’t understand how these cells present in those organs, and how they progress until the end. That’s why I think it’s the biggest challenge in the endometriosis field because if we understand more we will come up with better treatments.
Teresa Götz: Could you try to summarize your work for our readers, for the patients?
Dr. Ayse Nihan Kilinc: In my research, we are in close collaboration with surgeons because we are using human patient samples. Specifically, we acquire endometrial pipelle biopsies following surgeries, allowing us to isolate cells from these patients. To recreate the intricate patient environment in vitro, we employ 3D cultures known as organoid cultures.
By using these 3D biomaterials, I can mimic the endometrium, which is a soft tissue, but also because the lesions can be found in stiffer microenvironments because of fibrosis and they can also present in the muscle. We can simulate this by using 3D biomaterials making them stiffer similar to the muscle and fibrotic environment.
This allows me to monitor how the endometrial cells behave in the endometrium versus how they behave in a muscle tissue or stiff microenvironment. It was interesting to see that we could mimic the lesion behavior in the stiff microenvironments. For example, adenomyosis, which is defined as the presence of endometrial-like cells in the muscle tissue of uterus called as myometrium.
We know this, because we have patient lesion images that were acquired by microscopy and 3D reconstruction, which gives us the morphological features of the adenomyosis lesion, and we could mimic this morphology in the in vitro. Which is very important because then we can understand how these cells behave and consequently, find better treatments.
What I find particularly fascinating is the distinct behavior of these cells in a muscle-like environment. They start growing and invading their microenvironment which might tell us that in the patients, these endometrial epithelial cells might gain invasive-like potential and they start growing and invading the muscle tissue and leads to progression of the disease.
Teresa Götz: You can monitor the materials with tissue, but you can’t do it in the patient. It’s very important to have a good way to monitor or do experiments in the lab. The better it resembles the real tissue of the patient, the better your results are.
Dr. Ayse Nihan Kilinc: Exactly! Because, we have the opportunity to obtain both control patients and patients with the disease, along with their endometrial tissue and lesions. This is very important because it allows us to explore donor differences, comparing individuals with and without endometriosis. Using patient samples and primary cells is fundamental to gaining insights in this field.
Furthermore, I used microscopy techniques which has enabled me to capture time-lapse footage of cell progression and behavior. This aspect is particularly intriguing, given the limited ability to monitor such dynamics in patients directly. Hopefully, this will contribute valuable information to our understanding of endometriosis.
Additionally, we use microfluidic devices in the lab to better replicate organ phenotypes. Given the complexity of endometriosis, mimicking the microenvironment becomes crucial, involving various cell types such as immune cells, endothelial cells, and fibroblasts. These cells secrete both biochemical and biophysical factors, which are challenging to combine in vitro.
However, with the use of microfluidic devices, we can successfully integrate all these cell types. Creating a more accurate representation of the patient microenvironment is key to understanding the origin and progression of these cells, especially in their interaction with other cell types. Developing these tools is a significant aspect of our efforts to understand endometriosis in vitro.
Teresa Götz: That’s fascinating. Do you have future research goals?
Dr. Ayse Nihan Kilinc: In the other project that I’m working on, we are trying to mimic the endometrium by using these microfluidic tools. Also, the spatial organization of the cells in the endometrium is very important. That’s why those tools allow us to mimic the extracellular matrix, the microenvironment and having the different cell types, and also their spatial organization.
Now I’m also working on another project to mimic the endometrium and how the different layers of endometrium are generated. In the future, I really want to mimic the normal endometrium and also the disease endometrium on a chip. This will allow us to understand behavior of the cells and it will be really important for drug testing because there are not drugs to fully treat endometriosis.
Teresa Götz: That’s also really important that you don’t need a lot of animals to test it. It’s safer for the humans who tested first.
Dr. Ayse Nihan Kilinc: Exactly. It is difficult to work with animals because mice don’t have menstrual cycle and endometriosis and only non-human primates can have endometriosis because they are very similar to humans. They have a very similar menstrual cycle to humans and their physiology and hormonal responses are similar.
However, for sure there are also ethical issues and concerns to use non-human primates. That’s why I think it’s very critical, especially in the endometriosis research, to generate better patient mimicking in vitro tools to really cure the disease.
Teresa Götz: Because you are in the biophysical and biological field, do you work with other fields? I think with clinicians. Who’s in your team?
Dr. Ayse Nihan Kilinc: We are a very multidisciplinary team actually. We are in close collaboration with surgeons, and we receive the tissues from them. Also we have biologists like me in the lab and also we have biomaterials experts to generate these complex biomaterials to create a human-like environment. Also, we have mechanical engineers in the lab to generate those devices, those microfluidic devices.
Also, I think the biggest collaboration is with the patients. I’m thankful to them that they are actually donating their tissues to us. We should be always thankful to them because they contribute a lot to our research. I hope in return we can do a good job and cure this disease. This is what I hope and I believe actually one day we will be able to better understand and cure this disease.
Teresa Götz: I think this is a very good message for the patients. However, is there anything else you would like to share with the patients?
Dr. Ayse Nihan Kilinc: Actually, I think now I’m more hopeful because I can see there’s more raised awareness for endometriosis than how it used to be. But still I think we need to get more attention and this is what we are trying to do as well by showing the importance and how complex this disease is.
Hopefully one day we will bring it to the attention like cancer which will lead us more funding, more grants for the endometriosis research. There will be more researchers working on endometriosis and hopefully we will cure this disease. Because before getting into endometriosis research, I wasn’t aware that it was a neglected disease for a long time.
Teresa Götz: My final question is: what do you think about digital self-help?
Dr. Ayse Nihan Kilinc: I think I’ve found it very helpful. I think for patients it’s very important to get accurate information about the disease and the latest research, which will give them hope. I think it’s very important because in the app there are psychologists, support groups, and doctors giving accurate information.
It is important that doctors are also getting information from the patients because this disease has many variable symptoms. I think for the clinicians, it’s important to learn more about the varying symptoms and collect the data for a better diagnosis and for better research. I think that’s why it’s very important. I think you are doing a great job, and thank you so much for doing this.
Teresa Götz: Thanks so much for taking time for the interview and your great research.
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