Michele Plewes, PhD
Research Interests
- Hormone-driven metabolic control of fertility
- Metabolic drivers of ovarian aging and endocrine decline
- Organelle coordination in steroid hormone synthesis
- Gonadotrophin signaling in reproductive cell fate decisions
- Machine learning–based models for individualized reproductive care
How Hormones Reprogram Cell Metabolism to Control Fertility
Fertility depends on the ability of ovarian cells to rapidly convert metabolic inputs into steroid hormones that support ovulation, implantation, and pregnancy. At its core, this process requires precise coordination between mitochondria, lipid metabolism, and hormone signaling. My research asks a simple question: how do hormones reprogram cellular metabolism to support steroid hormone synthesis, and how does this process fail in infertility and ovarian aging? By examining how hormone signaling reshapes cellular metabolism and organelle function, my work defines the mechanisms that govern steroid hormone production and reproductive health.
A Mechanistic Framework for Reproductive Health
Rather than treating infertility as a downstream clinical outcome, my lab focuses on the cellular decision points that govern steroidogenesis, differentiation, and metabolic plasticity. Using multi-omics, molecular genetics, and advanced imaging, we define how lipid droplets, mitochondria, and signaling pathways are dynamically organized in response to hormonal cues. This mechanistic framework allows us to link basic cell biology to clinically relevant phenotypes such as poor ovarian response, premature luteinization, anovulation, and age-related reproductive decline.
Current Research Directions
1. Hormone-Driven Communication Between Lipid Droplets and Mitochondria
Sex steroid synthesis requires efficient transfer of cholesterol and metabolic intermediates to mitochondria. My lab investigates how gonadotropic signaling is routed to lipid droplets and mitochondria to coordinate lipid mobilization, mitochondrial metabolism, and steroid production. These studies define how hormone signaling is translated into metabolic output and how disruption of this process contributes to infertility.
2. Metabolic Remodeling During Ovulation and Luteinization
Ovulation and corpus luteum formation require rapid and coordinated metabolic reprogramming. We study how LH/cAMP/PKA signaling reorganizes lipid metabolism and mitochondrial biogenesis during this transition. By defining these pathways, we provide insight into the cellular basis of ovulatory failure and luteal dysfunction in reproductive disorders.
3. Mitochondrial and Lipid Dysregulation in the Aging Ovary
Age-related infertility reflects not only oocyte decline but also dysfunction in the surrounding granulosa cells that support oocyte maturation and hormone production. My lab examines how aging alters sterol homeostasis, mitochondrial specialization, and metabolic flexibility in granulosa cells, with the goal of identifying mechanisms that drive ovarian decline and potential targets to preserve reproductive health.
4. Metabolic Control of Ovarian Endocrine Longevity and Menopause
Sustained reproductive and endocrine function requires long-term maintenance of steroidogenic capacity in ovarian support cells. My lab investigates how cumulative disruptions in lipid metabolism, mitochondrial organization, and hormone signaling erode this capacity over time, leading to premature ovarian aging and early menopause. By defining the metabolic and organelle-level mechanisms that limit endocrine longevity, we aim to identify drivers of early reproductive decline and its downstream systemic health consequences.
5. Machine Learning–Driven Precision Tools for Reproductive Care
Clinical outcomes in reproductive medicine emerge from the interaction of patient physiology and treatment decisions. We use machine learning and artificial intelligence to model these interactions by training on large clinical datasets from women undergoing assisted reproductive technologies and integrating mechanistic molecular data, with the goal of developing predictive tools for individualized reproductive care.
Information
Graduate Training
PhD in Biological Education, University of Northern Colorado, Colorado
Post-Doctoral Fellowship
Reproductive Biology and Biochemistry
The Signal Transduction Laboratory, Department of Obstetrics and Gynecology
University of Nebraska Medical Center, College of Medicine, Omaha, Nebraska
- 09/2023-08/2027
Metabolic and Mitochondrial Signals During Ovulation
USDA NIFA
2023-67015-40795 (PI: Davis; Co-I: Plewes, Przygrodzka, Murry, Cupp) - 07/2024-07/2025
Sterol Metabolism and Mitochondria in the Aging Ovary
Nebraska Center for Women’s Health Research (PI: Plewes; Co-I: Zeljka Korade) - 01/2024-01/2027
Olsen Center for Women’s Health – (PI: Plewes) - 07/2024-07/2025
SREBF1/2 Signaling in Granulosa Cells: Steroidogenesis, Lipid Metabolism, and Mitochondrial Function
Nebraska Research Collaboration Initiative (PI: Plewes; Co-I: Drs. Davis, Korade, Schott, and Khalimonchuk) - 05/2023-05/2024
ShEEP Request for a Confocal Laser Scanning Microscope
US Department of Veterans Affairs
821-PS-45220 (PI: Bennett; Co-I: Plewes, McVicker, Viswanathan, Casey, Kharbanda) - 01/2021-01/2026
Mitochondria Dynamics and Steroidogenesis
VA-Career Development Award 2
1 IK2 BX004911-01 (PI: Plewes)
