# Neutral Sphingomyelinases and Bioactive Ceramides

> **NIH NIH R35** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $765,984

## Abstract

Abstract
 The overall goals of this research proposal are to define specific pathways of sphingolipid metabolism,
define specific roles, define mechanisms, and help place the field of bioactive lipids on solid mechanistic
grounds. Based on strong ongoing data, we propose the overall hypothesis that individual enzymes of
ceramide metabolism serve as transducers of specific inputs, and the product bioactive sphingolipids function
to mediate key responses. This proposal will develop this paradigm in the case of the DNA damage response
and other stimuli activating mammalian and yeast neutral sphingomyelinases in distinct compartments leading
to formation of compartmentalized and species-specific ceramides. We propose the following major goals: 1.
Advance our understanding of structure and activation of nSMase2; 2. Develop tools and approaches
to probe compartment-specific functions of bioactive sphingolipids and neutral sphingomyelinases; 3.
Define functions and mechanisms of neutral sphingomyelinases in the nucleus, especially in the DNA
Damage Response; and 4. Define mechanisms of regulation of protein phosphatases by ceramides. Taken
together, we endeavor to advance our understanding of bioactive sphingolipids and reduce the complexities of
the field to manageable and specific components that promise to shed important light on how these specific
pathways function, and their specific roles in stress responses. The ongoing results are defining totally
unexpected roles for neutral sphingomyelinases in distinct compartments, including the eukaryotic DNA
damage response through a nuclear lipid-mediated pathway. These are critical towards the understanding of
human disease (cancer) and therapeutics.

## Key facts

- **NIH application ID:** 10168016
- **Project number:** 2R35GM118128-06
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** YUSUF AWNI HANNUN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $765,984
- **Award type:** 2
- **Project period:** 2016-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168016

## Citation

> US National Institutes of Health, RePORTER application 10168016, Neutral Sphingomyelinases and Bioactive Ceramides (2R35GM118128-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10168016. Licensed CC0.

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