# Fostering patient-oriented research in cardiometabolic disease pathogenesis and prevention

> **NIH NIH K24** · UNIVERSITY OF WASHINGTON · 2021 · $118,553

## Abstract

The overarching goal of this proposal is to facilitate mentored training of junior investigators in the conduct
of high-quality patient-oriented research into cardiometabolic disease pathogenesis. The PI is an Associate
Professor of Medicine at the University of Washington whose research program to date has focused on the
neurobiological basis of obesity and abnormal glucose metabolism. The current proposal broadens the impact
of this work to include cardiovascular disease (CVD) outcomes. The candidate has a productive track record of
research mentorship of Fellows and junior faculty clinician-investigators, including K awardees, and academic
leadership in promoting mentorship at the departmental level. During this award, the PI will mentor a spectrum
of trainees from fields including endocrinology and metabolism, cardiology, pediatrics, and maternal-fetal
medicine. The PI will take didactic courses and engage in one-on-one coaching with experienced senior
investigators to build mentoring skills. The PI's research program is currently focused on translational studies
of cellular processes consistent with possible damage to the primary body-weight and glucose-regulating
region of the hypothalamus—the arcuate nucleus. Studies in rodent models show that diet-induced weight gain
is dependent on an inflammatory cellular response, known as gliosis, within the arcuate nucleus of the
hypothalamus. Gliosis progresses with continued dietary exposure, eventually showing signs of neuron loss.
Importantly, gliosis is detectable in mice and humans by magnetic resonance imaging (MRI). Using MRI, the PI
discovered the first evidence of hypothalamic gliosis in obese humans. The investigators have gone on to
show that hypothalamic gliosis 1) is independently related to insulin resistance in humans, 2) correlates with
increased levels of visceral fat, 3) is present in obese children, 4) is exacerbated in type 2 diabetes mellitus
(T2D), and 5) is improved by Roux-en-Y gastric bypass surgery. Our current projects seek to determine the
relationship of hypothalamic gliosis to T2D and the development of glucose intolerance as well as whether
hypothalamic gliosis is reversed by obesity treatment. The proposed research extends this work to investigate
the implications of hypothalamic gliosis for CVD. Aim 1 tests the relation of hypothalamic gliosis to CVD in
humans. To do this, the PI and trainees will conduct an ancillary study to the Framingham Heart Study (FHS).
Aim 2 uses an epidemiologic approach to examine dietary risk factors for hypothalamic gliosis within FHS. Aim
3 seeks pilot and feasibility data relating atherosclerosis via carotid imaging and autonomic dysfunction to
hypothalamic gliosis. A Mentoring Aim will advance the group's methodology for assessing dietary exposure.
Completion of these Aims could provide novel insights into the potential role of the central nervous system in
CVD development and critical scientific rationale for future K- and R- level st...

## Key facts

- **NIH application ID:** 10199013
- **Project number:** 5K24HL144917-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Ellen A Schur
- **Activity code:** K24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $118,553
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199013

## Citation

> US National Institutes of Health, RePORTER application 10199013, Fostering patient-oriented research in cardiometabolic disease pathogenesis and prevention (5K24HL144917-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10199013. Licensed CC0.

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