# Ceramide Activated Protein Phosphatases

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $375,618

## Abstract

Ceramide constitutes a family of closely related molecules that function as bioeffector
lipids with roles in the regulation of stress responses and growth/death of various human
cancer cells. Critical missing elements in our understanding of ceramide stem from the
lack of defining compartment-specific functions of ceramides and from lack of molecularly-
defined targets of action. Studies in our lab supported by this project have identified
ceramide-activated Ser–Thr phosphatases (CAPPs), specifically PP1 and PP2A as direct
targets activated by ceramide in vitro. Recent results have provided us a breakthrough in
defining a specific pathway of ceramide generation at the plasma membrane (PM). Here,
we will investigate the hypothesis that ceramide generated at the PM acutely activates
PP1α that leads to the dephosphorylation of distinct proteins, launching a distinct program
of regulation of cell adhesion and migration. We are also developing a novel assay to
quantitate PM ceramide specifically. With this breakthrough, we will address these aims:
Aim 1. Develop a quantitative assay to measure ceramide generation at the PM and
define key enzymes of ceramide metabolism in this compartment (steady state). Aim 2.
Define stimulus-induced formation of PM ceramide and the mechanisms involved. Aim 3.
Define biochemical mechanisms of regulation of PP1a by PM ceramide. Taken together,
these approaches should result, for the first time, in clearly defining a specific, direct, and
relevant target for ceramide action (PP1) with a specific function in mediating the effects
of PM ceramide on cell adhesion and migration.

## Key facts

- **NIH application ID:** 10886804
- **Project number:** 5R01CA218678-07
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** YUSUF AWNI HANNUN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,618
- **Award type:** 5
- **Project period:** 2018-07-12 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886804

## Citation

> US National Institutes of Health, RePORTER application 10886804, Ceramide Activated Protein Phosphatases (5R01CA218678-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10886804. Licensed CC0.

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