# Control of vesicular trafficking in the hepatocyte

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $685,454

## Abstract

Abstract
 This is the first competing renewal of a collaborative project between the groups of Dr. Allan Wolkoff and
Dr. Ana Maria Cuervo to investigate the role of endocytic/lysosomal processes in liver pathophysiology. During
the previous period, we developed technology to dissect the molecular mechanism regulating trafficking of the
vesicular components that participate in these processes. We also made the original discovery that endocytic
and autophagic pathways are tightly interrelated functionally and that dysfunction of these processes can lead
to dysregulation of lipid and carbohydrate metabolism in the liver. We now intend to continue this line of studies
focusing on a selective form of autophagy, chaperone-mediated autophagy (CMA) to test our working
hypothesis that CMA malfunctioning could contribute to the pathogenesis of metabolic syndrome, non-
alcoholic fatty liver disease (NAFLD) and liver fibrosis.
 We propose that 1) reduced hepatic CMA activity as a result of dietary challenges and aging contributes to
accelerate progression of fatty liver disease and that 2) enhancing this form of autophagy could be a
successful intervention to prevent progression of fatty liver Disease
 To test this hypothesis we intend to: 1) determine the molecular basis of dietary-induced hepatic CMA
dysfunction both in mouse models and NAFLD patients; 2) characterize the spatiotemporal sequence of CMA
changes in the fatty liver and during liver fibrosis; 3) test if genetic or chemical enhancement of CMA is
effective in protecting lipid challenged livers against lipotoxicity and disease progression.
Significance: This study will elucidate how a functional decline of CMA contributes to fatty liver disease and
liver fibrosis. Our findings could help in developing new approaches to protect the liver from lipotoxicity and to
reduce progression to liver fibrosis.

## Key facts

- **NIH application ID:** 10129358
- **Project number:** 5R01DK098408-09
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** ANA MARIA CUERVO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $685,454
- **Award type:** 5
- **Project period:** 2013-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129358

## Citation

> US National Institutes of Health, RePORTER application 10129358, Control of vesicular trafficking in the hepatocyte (5R01DK098408-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10129358. Licensed CC0.

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