# Mitochondrial Dynamics and Steroidogenesis

> **NIH VA IK2** · OMAHA VA  MEDICAL CENTER · 2024 · —

## Abstract

Candidate - The following application is intended to initiate the research career of Michele Plewes, PhD,
within the VA Nebraska Iowa Health Care System under the mentorship of John Davis, PhD, a VA Senior
Research Career Scientist and a well-respected, VA-funded reproductive endocrinologist for the past 30 years.
Dr. Plewes received her PhD in Biology in 2018 and is currently completing her postdoctoral training focused
exclusively in reproductive health research, including molecular endocrinology and steroidogenesis.
Environment - The University of Nebraska Medical Center is adjacent to the Omaha VA Medical Center where
strong scientific relationships have been established to complete the proposed studies. The research
environment is collegial and supportive with a multitude of opportunities for collaboration with other research
scientists. Specifically, Dr. Plewes will have the opportunity to discuss and present her work for crucial feedback
and direction from senior VA researchers. In her time as a postdoctoral associate, Dr. Plewes has been invited
to present her novel research findings twice at the VA research seminar series and will continue to seek feedback
from senior VA researchers, including her VA mentors. Research – Dysregulation of sex steroid synthesis and
secretion is a leading cause of infertility in both male and females. Infertility affects 1 in every 6 couples, with
male infertility playing a primary factor in a third of all cases. Moreover, infertility affects about 10 percent of the
female population (6.1 million) in the United States; about 100,000 female Veterans of reproductive age.
Considering the number of men and women who suffer from infertility and secondary affects associated with
dysregulation of sex steroid biogenesis understanding mechanisms that regulate PKA signaling and mobilization
of substrate for steroid production hold great potential to positively impact reproductive health and overall quality
of life. The proposed studies are expected to provide new information about the extramitochondrial role played
by mitochondrial Dynamin-GTPases in regulation of ovarian/testicular steroid synthesis and function. This
research proposal centers on the identification of the molecular mechanisms responsible for transmitting signals
from the outside environment to the mitochondria, initiating changes in mitochondrial structure and function, and
then translating molecular responses into changes in steroid biosynthesis. The proposed aims test the overall
hypothesis that LH/PKA regulation of mitochondria impacts mitochondrial structure, inter-organelle
communication and ultimately steroidogenesis. The central hypothesis will be tested by two specific aims. Aim
1: Determine the role of S-OPA1 in steroidogenesis. We will test the hypothesis that S-OPA1 serves as an AKAP
for PKA in LH-responsive cells. We will also test the hypothesis that mitochondrial PKA signaling is required for
optimal steroidogenesis. Aim 2: Determine th...

## Key facts

- **NIH application ID:** 10768650
- **Project number:** 5IK2BX004911-04
- **Recipient organization:** OMAHA VA  MEDICAL CENTER
- **Principal Investigator:** Michele R Plewes
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-02-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10768650

## Citation

> US National Institutes of Health, RePORTER application 10768650, Mitochondrial Dynamics and Steroidogenesis (5IK2BX004911-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10768650. Licensed CC0.

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