# ROLE OF S100A8/A9 IN BLOOD BRAIN BARRIER DYSFUNCTION AFTER SEPSIS

> **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $195,480

## Abstract

Project Summary
This proposal describes a five-year career development program designed to lead the PI to a career as an
independent clinician scientist studying the intersection of medical critical illness, neuroimmunology, and
vascular biology.
Research plan: Long term brain dysfunction, including cognitive and affective disorders, is common among the
1.3 million patients who survive critical illness every year in the United States. While the population impact of
brain dysfunction after critical medical illness is similar to morbidity associated with stroke and is an area of
growing scientific interest, few studies investigate the mechanism of these changes, and there is little scientific
basis for the rational design of treatments. The applicant has found that in a mouse model of sepsis, systemic
illness results in long lasting neuroinflammation with infiltration of inflammatory cells, changes in resident
microglial gene expression, and blood brain barrier dysfunction. In this proposal, the applicant will investigate
the role of an endogenous danger signal, the protein S100A8/A9, in sustaining neuroinflammation and blood
brain barrier dysfunction in a mouse model of sepsis, and determine if blockade of S100A8/A9 signaling
ameliorates these effects. He will study the role of S100A8/A9 both in an in vitro model system and in vivo
using a combination of pharmacologic and genetic approaches. These questions will also be extended to post
mortem studies of neuropathology and gene expression in the brains of patients with sepsis.
Applicant: The applicant holds M.D. and Ph.D. degrees and has completed specialty training in Internal
Medicine and Pulmonary and Critical Care Medicine. He has previous experience in neuroscience research
and using mouse models to study normal brain physiology and disease. The career development plan
includes a period of mentored research aimed at developing new knowledge in both immunology and vascular
biology that will greatly enhance his existing training and allow him to develop as an independent investigator
in studying an intrinsically interdisciplinary problem in translational neuroscience. The training will include
learning research techniques and acquiring scientific knowledge in the laboratories of and through meetings
with the mentors and key collaborators, as well as didactic training, seminars, lab meetings, topic focused
working groups, and national meetings. The training plan includes didactic training in grant writing and
responsible conduct of research. The research environment provides intellectual interaction with investigators
from neuroscience, immunology and vascular biology, as well as basic and clinical/translational scientists.
Technology for advanced imaging, gene expression, and immunophenotyping is available. These
opportunities will allow the applicant to be guided in developing both powerful investigative techniques and the
intellectual tools for an independent career in a clinically important ...

## Key facts

- **NIH application ID:** 9878934
- **Project number:** 5K08NS101054-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Benjamin Herschel Singer
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,480
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878934

## Citation

> US National Institutes of Health, RePORTER application 9878934, ROLE OF S100A8/A9 IN BLOOD BRAIN BARRIER DYSFUNCTION AFTER SEPSIS (5K08NS101054-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878934. Licensed CC0.

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