Michele Plewes, PhD

Assistant Professor

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Phone: 402-559-5445

Research Interests

• Gonadotrophin signaling
• Ovarian aging
• Lipid metabolism (sterol metabolism and lipid droplet biology)
• Mitochondrial function

Mitochondrial research is on the rise across the biomedical sciences, impacting nearly all areas of cell biology and medicine. Mitochondria influence cellular physiology by undergoing functional and morphological changes in response to genetic, metabolic, endocrine, and paracrine signals, all of which contribute to disease complexity. This uniquely places mitochondria as a key cellular gateway to the intersection of the cell and its environment. Understanding the basic physiological processes that regulate sex steroid synthesis is my current scientific passion and focus, particularly exploring how hormones induce changes to mitochondria and cholesterol mobilization for optimal progesterone and testosterone biosynthesis.

Project 1: Gonadotrophic Signaling and Steroid Synthesis in Reproductive Health

Infertility affects approximately one in six couples of reproductive age worldwide, posing significant challenges. This condition has far-reaching implications, impacting not only physical health but also the emotional and economic aspects of individual, couple, and societal well-being. A primary cause of infertility in both males and females is the dysregulation of sex steroid synthesis and secretion. Given the extensive number of individuals facing infertility and the related issues arising from the dysregulation of sex steroid synthesis, our research is of paramount importance. We are dedicated to understanding the mechanisms that regulate Protein Kinase A signaling and the mobilization of substrates for steroid production. These insights have the potential to markedly improve reproductive health and enhance overall quality of life. Our team's focus is on deciphering the molecular mechanisms responsible for the transmission of gonadotrophic signals from the external environment to lipid droplets and mitochondria within cells. We aim to understand how these signals prompt changes in lipid droplet lipolysis and mitochondrial structure and metabolism. Our goal is to translate these molecular responses to offer new perspectives and solutions in the realm of reproductive health. 

Project 2: Lipid Signaling and Mitochondrial Dynamics in Ovulation and Fertility

Infertility presents challenges for both women and domestic farm animals, with anovulation further complicating the reproductive landscape. The ovulatory period is a critical phase for fertility, involving the intricate processes of reactivating oocyte meiosis, generating a rupture pore at the follicle apex, and initiating cellular differentiation and tissue remodeling to form the corpus luteum. These processes are orchestrated by endocrine signals that significantly influence the developmental potential of resultant embryos, playing a fundamental role in the successful establishment of pregnancy. The ovulatory period stands as a key determinant of fertility, with emerging research indicating a link between gonadotropin signaling, lipid metabolism, and mitochondrial function in achieving successful ovulation. Our research focuses on how LHCGR signaling impacts lipid signaling pathways, encompassing aspects such as lipid droplet formation, as well as mitochondrial biogenesis during the stages of ovulation and luteinization. By delving into these aspects, we aim to shed light on the intricate processes involved in ovulation. Our approach seeks to unravel the multifaceted mechanisms controlled by LHCGR signaling, providing a holistic understanding that could pave the way for novel strategies for addressing infertility. 

Project 3: Lipid Metabolism and Mitochondrial Metabolic Reprogramming in the Aging Ovary

Recent societal shifts have led to a notable increase in first-time mothers over 35, a figure that has risen more than five-fold since 1970. This trend is of particular importance as female fecundity typically begins to decline at age 32, with a significant decrease in ovarian egg quality and quantity after 35. Central to this issue of age-related fertility decline are ovarian granulosa cells, which are pivotal in regulating follicular development and oocyte maturation. These cells perform multiple functions, including providing structural support, synthesizing steroid hormones, secreting growth factors, and regulating the ovarian microenvironment. As women age, the quantity of high-quality follicles naturally decreases due to a process known as atresia. Yet, the mechanism of granulosa cell apoptosis in women of advanced reproductive age are not well-understood. This issue is compounded by a documented link between advanced reproductive age and reduced steroid synthesis in the ovaries, highlighting the vital role of granulosa cells in fertility. Our research is dedicated to exploring the molecular mechanisms behind granulosa cell function, aiming to deepen our understanding of age-related fertility issues and health disparities. My lab is focused on uncovering the processes that drive the development of high-quality ovarian follicles and identifying the key lipid signaling pathways that are crucial for effective steroid synthesis and optimal granulosa cell function. We hypothesize that precise regulation of sterol homeostasis and mitochondrial function is essential for the health and efficacy of these cells. By unraveling these mechanisms, we aim to develop new strategies to address infertility and create advanced ovary-based contraceptives.

Farzan Tamanaeifar, PhD student (VA Research Week 2024)

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Gracyn Little (SURP student 2024)

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Plewes, Davis, and Clark Lab

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Kimber Sprout (SURP student 2022)

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Alexis Schrouder presenting her summer research for the Dept. of OB-GYN (SURP student 2023)

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Alexis Schroeder (SURP student 2023)

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