# Dissecting the molecular mechanisms underlying lipotoxicity in the kidney.

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2021 · $33,799

## Abstract

Abstract
Chronic kidney diseases affect millions around the world. A combination of genetic and environmental factors
can contribute to the progression of kidney disease. Obesity is a risk factor for metabolic diseases like type 2
diabetes (T2D), which has been highly associated with kidney disease progression. T2D is often characterized
by high levels of lipids in the bloodstream, which can be toxic to non-adipose tissues like the kidney. The
consequent lipotoxicity may injure kidney cells, contributing to the pathogenesis of diseases like diabetic
nephropathy, but the specific cellular effects of lipotoxicity in the kidney are unknown. The first aim will identify
which FFAs are lipotoxic to kidney tubular epithelial cells and what cellular stress responses they induce, using
readout methods like ER stress, cell viability, and transcriptomics. The second aim will use Perturb-Seq, which
combines CRISPR screens with single-cell RNA sequencing, to identify genes whose perturbations induce
transcriptional signatures of cellular stress states, followed by validation in kidney organoids. Ultimately, these
experiments will reveal the genes and pathways that mediate FFA-induced lipotoxic injury in kidney cells. Given
the largely unmet need for kidney disease therapies, our study will provide a step towards revealing new targets
as well as expanding our knowledge on the fundamental mechanisms underlying kidney disease.

## Key facts

- **NIH application ID:** 10247515
- **Project number:** 5F31DK126252-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Choah Kim
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,799
- **Award type:** 5
- **Project period:** 2020-09-30 → 2023-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247515

## Citation

> US National Institutes of Health, RePORTER application 10247515, Dissecting the molecular mechanisms underlying lipotoxicity in the kidney. (5F31DK126252-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247515. Licensed CC0.

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