# Project 1: Acid Ceramidase-S1P Metabolic Axis and Regulation of Tumor Resistance to Apoptosis

> **NIH NIH P01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $329,456

## Abstract

SUMMARY 
This proposal is designed to test our novel hypothesis that cellular stress-mediated acid ceramidase (AC) 
activation, invoked by radiation or chemotherapy, leads to resistance to apoptosis by induction of S1P-S1PR2- 
mediated AKT activation, leading to nuclear PTEN export. As a corollary, we also hypothesize that targeting 
AC inhibits S1P/AKT signaling, overcoming cell death resistance in the treatment of prostate cancer. We plan 
to dissect mechanisms of resistance at the molecular and pharmacological level to develop novel treatment 
strategies as follows: Specific Aim 1. Determine the mechanisms of AC-dependent resistance to cell death 
following therapy stress. Specific Aim 2. Determine the therapeutic roles of targeting the AC/SK1/S1P/AKT axis 
to overcome therapy resistance for the treatment of prostate cancer. Data obtained from these studies will 
provide novel mechanism-based therapeutic strategies to overcome resistance by targeting AC and/or SK/S1P 
signaling in solid tumors, including prostate, kidney/bladder and/or liver tumors, which are within the focus of 
this Program Project.

## Key facts

- **NIH application ID:** 9980708
- **Project number:** 5P01CA203628-05
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** CHRISTINA VOELKEL-JOHNSON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $329,456
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980708

## Citation

> US National Institutes of Health, RePORTER application 9980708, Project 1: Acid Ceramidase-S1P Metabolic Axis and Regulation of Tumor Resistance to Apoptosis (5P01CA203628-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980708. Licensed CC0.

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