# Regulation of Membrane Lipid Homeostasis

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2024 · $14,445

## Abstract

Project Summary
The lipid composition of cell membranes controls bilayer permeability and fluidity as well as the folding and
activity of integral membrane proteins, which comprise ~30% of the human proteome. Consequently, the lipid
composition of membranes is subject to tight homeostatic control. Over the past 60 years, we have learned a
tremendous amount about membrane lipid cell biology, largely from model organisms because forward
genetics in cultured human cells remained challenging. CRISPR technology now permits a direct examination
of these cellular functions in human cells, opening up a new era of mammalian cell genetics.
Our MIRA research strategy is to apply mammalian cell genetics to long-standing questions in cell biology,
specifically focusing on the regulation of membrane lipid homeostasis. Over the next 5 years, we will use
genetics to address two challenges. For Challenge #1, we will identify new regulators of plasma membrane
lipid composition. For Challenge #2, we will discover the mechanism of lysosomal fatty acid export by
characterizing genes required for the assimilation of low-density lipoprotein (LDL)-derived fatty acids.
Overall, these proposed MIRA studies will make fundamental contributions to the fields of membrane biology,
intracellular lipid transport, LDL receptor function/endocytosis, the SREBP pathway, and regulation of lipid
synthesis. Given that modulation of cholesterol synthesis and LDL receptor function are primary interventions
in the treatment of hypercholesterolemia, these studies may identify new therapeutic targets for the prevention
of heart disease, a leading killer of adults in the United States.

## Key facts

- **NIH application ID:** 11035360
- **Project number:** 3R35GM149312-02S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** PETER J. ESPENSHADE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $14,445
- **Award type:** 3
- **Project period:** 2023-06-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11035360

## Citation

> US National Institutes of Health, RePORTER application 11035360, Regulation of Membrane Lipid Homeostasis (3R35GM149312-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11035360. Licensed CC0.

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