Project Team
Nicole Donnellan, MD, Program Director of the ob-gyn residency and of the Fellowship in Minimally Invasive Gynecologic Surgery at Unversity of Pittsburg Medical Center, Magee-Womens Hospital
Christopher Dupont, PhD, Associate Professor in Genomic Medicine, Environment & Sustainability, and Synthetic Biology, the J. Craig Venter Institute
Richard Scheuermann, PhD, Director of the JCVI La Jolla Campus & Informatics, the J. Craig Venter Institute
Gene Tan, PhD, Assistant Professor in the Infectious Disease Group, the J. Craig Venter Institute
Amy Proal, PhD, President/Microbiologist, PolyBio Research Foundation
Project summary:
Dr. Nicole Donellan will collect endometriosis tissue for the study
A collaborative project to determine if infection (including that driven by the SARS-CoV-2 virus) and the accompanying host immune response modulate genetic changes that contribute to the development of endometriosis. Endometriosis tissue will be collected during surgery from women with the condition. The project team will use state-of-the-art sequencing methods to detect pathogens/organisms including DNA & RNA viruses, bacteria, fungi, and their gene expression profiles in the tissue samples. In parallel, single nuclei RNA sequencing will be used to define the transcriptional landscape of the the host immune system and blood vessels in tissue, with machine learning used to correlate unique genetic changes with the potential presence of a particular pathogen or collection of pathogens.
Project background:
Endometriosis is a painful disorder in which tissue similar to the tissue that normally lines the inside of the uterus — the endometrium — grows outside the uterus. Endometriosis most commonly involves the ovaries, fallopian tubes and the tissue lining the pelvis. In some cases endometrial-like tissue may be found beyond the area where pelvic organs are located. While surgery can be used to remove endometriosis tissue in patients with the condition, little research has been done to reveal “root cause” biological factors that may contribute to endometriosis disease progression. Women with endometriosis consequently have no treatment options beyond surgery for symptom relief, and no biomarkers exist for accurate diagnosis of the disease in a standard clinical setting.
Endometriosis is characterized by dysregulated tissue proliferation and angiogenesis: the formation of new blood vessels. Pathogens – including viruses – can regulate angiogenesis via a number of mechanisms. Many pathogens can also alter expression and function of genes that control cell proliferation. Several recent endometriosis tissue studies have identified changes in host immune signaling that could result from pathogen or organism activity. High estrogen production is also a consistently observed endocrine feature of endometriosis and pathogens are capable of modulating estrogen signaling. For example, one team showed that the SARS-CoV-2 spike protein directly binds and modulates estrogen receptor activity.
SARS-CoV-2 in endometrial gland epithelium (asterisk) and stromal cells (hash) in an endometrial tissue sample. PMID: 36517603
The current study will consequently be the first in the world to used advanced sequencing technologies to test the hypothesis that pathogen activity may contribute to the endometriosis disease process. Analysis will account for the possibility that infection with the SARS-CoV-2 virus could be connected to certain endometriosis cases. SARS-CoV-2 is capable os infecting endometrial tissue (the ACE2 receptor that the virus uses to enter cells is highly expressed in human endometrial stromal cells). Indeed, in an important recent autopsy study, SARS-CoV-2 was identified in endometrial gland epithelium and stromal cells of tissue collected from a pre-menopausal woman. The virus was also identified in ovary and uterus tissue from other study participants.