# Sphingolipids in Cancer Biology and Therapy

> **NIH NIH P01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $1,299,443

## Abstract

The overall organizing hypothesis of this Program posits that bioactive sphingolipids function
as important regulators of several key tumor cell attributes, including tumor initiation,
differentiation, growth, apoptosis, senescence, inflammation, invasion, and metastasis. As a
corollary, enzymes of sphingolipid metabolism are emerging as specific and novel targets in
modulating these important cancer attributes. Unfortunately, the study of bioactive lipids is rife
with complications, both conceptual and technical and thus the study of lipids necessitates the
collaborative interactions of various disciplines and specialized cores. Thus, we have evolved 4
distinct projects that collaborate to investigate the overall hypothesis. These projects address
highly interrelated metabolic pathways that converge on the Golgi apparatus. Each project has
identified a key node in these pathways that constitutes a specific vulnerability in the target cancer
under study. Thus, Project 1 will test and advance the hypothesis that the novel acid
sphingomyelinase/ceramide kinase pathway defines a previously unappreciated mechanism
regulating invasiveness and metastasis of breast cancer. Project 2 will test the hypothesis that
alkaline ceramidase 2 is a novel tumor suppressor whose suppression promotes development
and progression of hepatocellular carcinoma. Project 3 will test the hypothesis that sphingosine
kinase 1 (SK1) is a therapeutic target for p53 null and mutant cancers, and that Ser/Gly
deprivation can be harnessed therapeutically to degrade SK1 and lead to cancer cell death.
Project 4 will test the hypothesis that sphingomyelin synthase 1 is an indispensable novel
regulator of proliferation of GATA1-positive AMLs (including the poorly studied acute erythroid,
M6 and megakaryocytic, M7 leukemias) and a potential novel target for improving the dismal
therapeutic response of these leukemias. These 4 projects will be supported by two unique
research cores: The Lipidomics Shared Resource which will provide advanced analytical lipid
chemistry and flux analysis, and by a Sphingolipid Animal Cancer Pathobiology Shared
Resource that focuses on mutants/knock outs in enzymes of sphingolipid metabolism and models
of in vivo carcinogenesis. It has recently introduced biobanking and CRISPR-mediated nock outs.
This Program group has been highly integrated and productive (having published in the past 5
years 76 manuscripts, 50 of which were in collaboration) and has advanced significantly our
understanding of sphingolipids (one of the last frontiers of basic research) in caner biology and
therapeutics. We are now poised to advance pre-clinical studies and translational research based
on our understanding of these novel pathways. These studies continue to identify novel targets
and strategies for cancer therapeutics.

## Key facts

- **NIH application ID:** 10247617
- **Project number:** 5P01CA097132-18
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** YUSUF AWNI HANNUN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,299,443
- **Award type:** 5
- **Project period:** 2003-08-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247617

## Citation

> US National Institutes of Health, RePORTER application 10247617, Sphingolipids in Cancer Biology and Therapy (5P01CA097132-18). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10247617. Licensed CC0.

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