# Anastasis: A Novel Cell Survival Mechanism

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2024 · $248,890

## Abstract

Project Summary
Anastasis is a newly discovered cell recovery mechanism that rescues apoptotic cells from the brink of
death. Challenging the classic view of irreversible apoptosis, we have discovered robust reversibility of
apoptosis in three types of mouse/rat primary cells, twelve human cancer cell lines, and egg chambers in fruit
flies. What are the physiological functions, pathological roles, and therapeutic potentials of anastasis?
Anastasis could be an unexpected cytoprotective mechanism for preserving terminally differentiated cells
and tissues that are difficult to replace, such as cardiomyocytes and neurons. If true, enhancing anastasis
may be beneficial for treating heart failure and brain injury. Besides, anastasis could be an unrecognized
escape tactic enabling cancer cells to survive cancer therapy, thereby contributing to disease recurrence. If
confirmed, suppressing anastasis in dying cancer cells may promote cancer cell death and reduce the chances
of recurrence. Anastasis may also play important roles in limiting apoptosis during embryonic development
and normal homeostasis. If identified, understanding its regulation can provide new insights into the control of
cell death and survival in physiological conditions. However, there are several challenges of testing these
hypotheses. It is difficult to track anastasis, especially in vivo, because cells that have reversed apoptosis are
morphologically indistinguishable from healthy cells. There are no anastasis-specific hallmarks identified, and
the regulators of anastasis remain undiscovered. Here, we will overcome many of these challenges by
developing a novel and highly specific tracking system to label anastatic cells for mammalian studies, and to
identify the key regulators of anastasis. To mark anastatic cells, we will create an anastasis biosensor
that can tag anastatic cells with permanent expression of a fluorescent protein only after they have
recovered from late-stage apoptosis. We will establish anastasis biosensor stable cell lines to determine
reversibility of apoptosis in vitro, and will employ biosensor xenografts to interrogate anastasis in vivo using
clinically relevant mouse models. To elucidate the mechanism of anastasis, we will identify its key
regulators, through proteomics, genetics, and pharmacological approaches. We will identify which genes
exhibit up- or down-expression (potential anastasis regulators, and therapeutic targets) during different
stages of anastasis, determine whether specific post-translational modifications distinguish anastatic cells,
establish whether cells that recover from different cell death inductions share similar molecular features, and
investigate how interfering with anastasis regulators could modulate the reversibility of apoptosis. We will
apply time-lapse live-cell confocal imaging to evaluate the functionality of anastasis biosensor,
characterize anastatic cells, and determine efficacy of anastasis-targeting agents in vitro, ...

## Key facts

- **NIH application ID:** 11033234
- **Project number:** 3R35GM150835-01S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ho Lam Tang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $248,890
- **Award type:** 3
- **Project period:** 2023-09-22 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11033234

## Citation

> US National Institutes of Health, RePORTER application 11033234, Anastasis: A Novel Cell Survival Mechanism (3R35GM150835-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11033234. Licensed CC0.

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