# Decoding the Brain-Liver Axis: Uncovering mechanisms of host defense

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $451,292

## Abstract

This research proposal seeks to uncover neuronal mechanisms orchestrating metabolic adaptations to
bacterial infections, specifically delineating the pivotal role of the brain-liver axis in modulating metabolic
responses. By combining the methods of neuroscience and immunology, the research aims to better
understand neuronal and hepatic responses to infections. I showed earlier that housing infected mice at
thermoneutrality instead of ambient room temperature better mimics human bacterial infections. For example,
infected mice at thermoneutrality develop severe hyperlipidemia, compromising survival. Here, I hypothesize
that circulating lipids are regulated by neuronal and hepatic mechanisms. In Goal 1, I will look for neurocircuits
in the hypothalamus that might monitor circulating lipoproteins and trigger counterregulatory responses. To do
this, I will use genetic mouse models and chemogenetics to stimulate and inhibit candidate neuronal clusters
during infections. In Goal 2, I will perform an unbiased screen to elucidate hepatic secretome using TurboID,
followed by targeted proteomics. I will target these hepatic factors in vivo to test their role in improving host
survival during bacterial infections. My approaches defining the molecular basis of hyperlipidemia in mouse
models are highly innovative and likely to provide novel insights into how circulating lipid levels determine host
survival.

## Key facts

- **NIH application ID:** 10950633
- **Project number:** 1DP2AI184813-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Joni Nikkanen
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $451,292
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10950633

## Citation

> US National Institutes of Health, RePORTER application 10950633, Decoding the Brain-Liver Axis: Uncovering mechanisms of host defense (1DP2AI184813-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10950633. Licensed CC0.

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