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Our laboratory is part of the Division of Reproductive Sciences and the Division of Reproductive Endocrinology within the Department of Obstetrics and Gynecology at the University of Colorado Anchutz Medical Campus in Aurora, Colorado. Our overall goal is to improve the health and well-being of women. In one central project, we are investigating mechanisms that lead to accelerated female reproductive aging, which can manifest when ovarian function ceases early in life relative to the expected time of menopause. Our group is focused on mechanisms that control primordial follicle growth activation (PFGA). The reason for this focus is that the rate of loss of the primordial reserve of follicles determines whether a woman will experience a 'normal' duration of ovarian function, or instead, face primary ovarian insufficiency (POI) where ovarian function ceases before the age of 40.
Approximately 1 in 250 women will experience POI prior to age 35, and 1 in 100 prior to age 40, An additional 5% of women experience ovarian failure between 40 and 45 years, outside the definition of POI. In combination, the cost of POI to individuals and to society is extraordinarily high. If afflicted with POI, women can face decades of increased risk for these problems of aging and their treatment limitations. Further characterizing the mechanism(s) that drive PFGA and thus ovarian aging will fill major gaps in our understanding of this critical biological process. This may lead to future interventions to slow ovarian aging and improve the health of women.
Blog Post 25: How random is ovarian aging?
November, 2021: Our work investigating ovarian aging using mathematical modeling continues, and we wrote up a blog post for a more general audience here. The post puts our recent work into context with several excellent "historical" publications, and argues that ovarian aging may arise as an "emergent behavior" that results from the action of individual primordial ovarian follicles. Is the mammalian ovary "a non-trivial, emergent, self-organizing system, with limited adaptive capacity?"
Lab Theme Highlight, Summer 2022: Mathematical Modeling of Ovarian Aging
In the fall of 2021, we resumed our long-time collaboration with Dr. Jay Emerson of the Yale University Department of Statistics and Data Science, and began to collaborate with Dr. Sean Lawley, who's in the Department of Mathematics at the University of Utah. A series of Zoom meetings and collaborative writing in our shared folder has led to our first manuscript on the topic, online August 22, 2022! Our paper "Recapitulating Human Ovarian Aging Using Random Walks" is now available at the journal PeerJ. We drew upon our prior work that identified the Integrated Stress Response pathway as a regulator of the cell cycle in ovarian follicles, and modeled dormant primordial ovarian follicles as undergoing random walks versus a threshold of growth. Remarkably, simulating hundreds of thousands of primordial follicles in this way recapitulates both the known pattern of follicle loss during aging, and also, the distribution that women undergo menopause. This project is ongoing, with new insights in the pipeline and exciting new interactions between biologists and mathematicians to look forward to! EASTER EGG: if you send an email to:
johnsonlab AT proton DOT me
with "SIM" in the subject line, we'll send you unique results of a random walk simulation of ovarian aging, using the R code developed for our paper, and run just for you.
Next, in a collaborative project with members of the Division of Urogynecology and Pelvic Floor Surgery, we are also investigating mechanisms that lead to the degeneration of pelvic floor support structures. We are focused on the cell and tissue biology of pelvic floor ligaments, as well as their biomechanical properties. Our goals here are to uncover preventative strategies to lessen the incidence of pelvic floor organ prolapse, and also reduce the recurrence of the condition.