# Crislip_F32_Childcare Supplement

> **NIH NIH F32** · UNIVERSITY OF FLORIDA · 2021 · $2,500

## Abstract

Project Summary:
Over half of Americans have hypertension and the majority do not have their blood pressure (BP) under control
even with treatment. Continued research in understanding BP regulation is needed to improve treatment efficacy
and prevention. BP regulation is influenced by the circadian clock as seen by its daily rhythm. BMAL1 is a core
circadian transcription factor which regulates the circadian clock feedback loop. BMAL1 also controls the
expression of thousands of genes important for physiological functions. Others have shown that male global
BMAL1 knockout mice (KO) have 10 mmHg lower mean arterial pressure (MAP) and lose their circadian rhythm
in BP compared to wildtype (WT). Because the kidney is a critical regulator of BP, we generated distal nephron-
specific BMAL1 KO that exhibit a difference in BP without loss of circadian rhythms in cardiovascular function.
Our preliminary data demonstrate that male KO have approximately 7 mmHg lower BP than WT. Interestingly,
this affect is sex-dependent and female KO have comparable BP to WT. The goal of this study is to determine
the molecular mechanisms by which sex hormones influence BMAL1-dependent BP regulation in the distal
nephron in males and females. Sex hormones have been linked to BP control previously. We hypothesize that
androgens in males influence distal nephron-specific BMAL1 BP regulation differently than ovarian hormones
do so in females. Experiments will address our hypothesis with two aims: Aim 1 will test the hypothesis that
male sex hormone signals mediate distal nephron-specific BMAL1-dependent BP regulation. Aim 2 will test the
hypothesis that ovarian hormones in females prevent distal nephron-specific BMAL1-dependent changes in BP.
Briefly, telemeter devices will monitor BP in WT and KO with and without gonadectomy and hormone
replacement. Biochemical assays will determine the role of distal nephron-specific BMAL1 on BP in these mice.
This proposal will examine the role of BMAL1 in BP control independent of circadian rhythms and explore the
novel difference demonstrated in males vs. females. This project will also provide essential training to help in
advancing my career by improving scientific communication and writing, strengthening critical thinking skills, and
providing mentorship opportunities. The scientific environment on campus is extremely supportive and
collaborative, additionally, the advisory committee (Drs. Karyn Esser, Andrew Liu, and Arlene Chapman) that Dr.
Gumz and I have assembled will be critical in my development. The inclusion of circadian biology principles in
the planning and analysis of these studies is a key innovation in the broader field of BP research. Our results
will improve the understanding of peripheral BMAL1 gene regulation and shed light on how versatile these
circadian genes are. Additionally, inclusion of females in our study will yield novel data on BMAL1-dependent
BP control that has not been explored before and will aide in b...

## Key facts

- **NIH application ID:** 10397263
- **Project number:** 3F32DK121424-02S1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Gene Ryan Crislip
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2020-03-15 → 2022-03-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397263

## Citation

> US National Institutes of Health, RePORTER application 10397263, Crislip_F32_Childcare Supplement (3F32DK121424-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10397263. Licensed CC0.

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