A new endometriosis cellular atlas provides more insight into

Could you please introduce yourself and tell us a little bit about your professional history?
At Cedars-Sinai in Los Angeles, I am an Associate Professor in the Departments of Obstetrics and Gynecology and Biomedical Sciences. In addition, I am the Associate Director of the Postdoctoral Scientist Program at Cedars-Sinai and the Director of the Women’s Cancer Research Program.

10% of women globally suffer from the gynecological disorder endometriosis. What is endometriosis, and why has it historically received so little attention?

Endometriosis is a disorder in which cells that resemble the uterine lining are located in the incorrect location. Endometriosis is frequently found in the ovaries or on the lining of the pelvic cavity, but in extremely rare circumstances, it can also be found in locations further away, such as the lungs (thoracic endometriosis).

Like the uterus, endometriosis lesions have the ability to bleed, develop, and even infiltrate nearby organs. Numerous issues result from this, including infertility and chronic, frequently incapacitating discomfort. Additionally, patients frequently experience systemic symptoms like gastrointestinal problems and increased pain sensitivity.

The lack of funds has hampered endometriosis research. Endometriosis is one of the most neglected diseases despite being incredibly common since many underfunded conditions disproportionately affect women. There are several causes for this, including societal attitudes about problems that only affect women, and endometriosis has received little attention from a medical, social, and political perspective.

However, I have hope that things are beginning to change and that endometriosis and other problems affecting women’s health are becoming more prominent. This should help us get more of the cash we need to help patients.

While most endometriosis patients identify as women and have uteruses, it’s crucial to keep in mind that transgender men and people without uteruses (due to hysterectomy or a congenital disorder, for example) can also be affected. It’s crucial that we include these patient populations in our research.

What is the present status of endometriosis treatment, and what is impeding its development?

Drugs that inhibit the growth of lesions by reducing estrogen levels in the body are typically used to treat endometriosis (such as combined oral contraceptives, or “The Pill”). Analgesics are frequently used by patients to assist them to control their pain. However, therapy frequently has negative side effects for patients, or after a while, the medication loses its effectiveness.

Because the underlying cause is still there, suppressing the lesions is not compatible with pregnancy and typically does not increase fertility. Surgery is sometimes performed on patients to remove or burn lesions. However, recurrence is rather frequent, and about 50% of individuals who have surgery will also have additional treatments.

It’s critical to understand that endometriosis is a chronic condition that takes years to treat. The best outcomes for patients are likely to be attained by comprehensive methods to care, which may include (as needed) cognitive behavioral therapy, mindfulness-based therapy, and physical therapy for pelvic floor dysfunction. To manage to live with endometriosis, many doctors advise a nutritious diet, proper sleep hygiene, and exercise.

What were your primary findings and how did you go about doing your study?
In the past five years, genomics has undergone a revolution that has made it much easier, less expensive, and quicker to examine individual cells. In contrast to the past, when cells would have been merged to make a single sample for examination, we can now generate data points for thousands of individual cells for each patient. For endometriosis, where the lesions can be small (typically only a few millimeters in diameter) and composed of numerous different cell types that work together to generate disease, this increased degree of precision makes a significant impact.

My lab gained proficiency in profiling human tissues using single-cell genomics, and we collaborated with pathologists and surgeons to produce an endometriosis cell atlas. We were able to demonstrate that endometriosis in the ovary (endometrioma) differs significantly from endometriosis in the pelvic cavity and that endometriosis cells react to female hormones in a manner distinct from womb cells. Additionally, we were able to demonstrate that endometriosis genetic mutations affect gene expression, which may aid endometriosis in changing the tissue it has invaded.

How will your research improve the treatment of endometriosis patients? What comes next for your research and you?

Large-scale genome-wide molecular profile data are lacking, which has hampered endometriosis research. We now have an important first look at the molecular profiles of human endometriosis thanks to studies like ours and others. Our team’s and other researchers’ efforts will continue to expand this significant resource and explore endometriosis characteristics in populations we were unable to study, such as endometriosis in teens or women without pain.

These data are currently being used in the lab to meet two important unmet clinical requirements. The first is to look for new endometriosis biomarkers that, when paired with data on lifestyle, genetics, and family history, may be used for diagnosis or individualized risk assessment. The second is to evaluate novel treatments designed to restore the endometriosis cells’ normal behavior.

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The Ph.D. of Kate Lawrenson
At Cedars-Sinai Medical Center in Los Angeles, I oversee a multidisciplinary research lab and have devoted my whole professional life to the investigation of unmet needs in women’s health. When I was a Ph.D. student, I initially became interested in endometriosis after meeting a patient who had the condition in one of the gynecological clinics where I was scouting participants for our study. I was deeply affected by the tale of her many unbearable symptoms, and I started looking for possibilities to conduct endometriosis research, initially concentrating on endometriosis-associated ovarian malignancies and eventually developing an endometriosis research program. This led to the creation of one of the few endometriosis cell line models, investigations into the genetic relationships between endometriosis and ovarian malignancies, and more, and most recently, an endometriosis single-cell atlas.

In order to understand molecular landscapes in disease, the Lawrenson Laboratory at Cedars-Sinai uses experimental bench research and bioinformatics, especially focusing on endometriosis and ovarian malignancies. Additionally, we conduct two clinical trials aimed at identifying novel biomarkers and therapeutic targets by investigating the origins of endometriosis and gynecologic malignancies.

Exactly what is “skin cycling” and should you give it a shot?

I’m also quite passionate about mentoring, especially when it comes to empowering women and disadvantaged groups. I’ve guided a number of students, fellows, interns, postdoctoral researchers, and staff scientists through fruitful career-enhancing research as the associate director of the postdoctoral scientist program at Cedars-Sinai. Through my leadership position as Director of the Women’s Cancer Research Program at Cedars-Sinai, I focus on developing multidisciplinary teams in endometriosis and women’s malignancies.

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