# Latexin function in the maintenance and regeneration of the hematopoietic system

> **NIH NIH R01** · NEW YORK BLOOD CENTER · 2024 · $427,000

## Abstract

ABSTRACT
The hematopoietic system is very sensitive to a variety of stresses. Radiation therapy commonly results in not
only acute hematopoietic suppression but also long-term bone marrow (BM) injury with increased risk of BM
failure or malignancy. Accumulation of damages during aging process is another type of stress on HSCs.
Enhancing HSC survival and maintaining their genomic integrity upon stress are crucial for preservation of HSC
self-renewal function and for protection against stress-induced BM injury. However, the underlying molecular
mechanisms are not well defined. No effective treatment has been developed to prevent or treat stress-induced
HSC damages and related pathological consequences. The primary goal of this project is to identify novel
pharmaceutical compounds and transcriptional mechanism that target a HSC stress regulatory protein, latexin
(Lxn), and to uncover the mechanisms that Lxn suppression results in radiation protection and HSC rejuvenation.
We have identified a novel Lxn inhibitor small compound and found that it significantly increases survival by
protecting HSCs via a newly identified canonical mechanism of carboxypeptidase A inhibition upon radiation.
Lxn deletion also mitigates aging-related functional decline of HSCs. We hypothesize that pharmaceutical and
transcriptional suppression of Lxn protects HSCs and blood system from stress (radiation and aging)-induced
functional decline via the upregulation of canonical CPA3 pathway. Aim 1 is to determine the molecular
mechanisms by which Lxn inactivation protects against radiation-induced BM injury via up-regulation of canonical
CPA3 pathway. Aim 2 is to identify the mechanism of action of Lxn lead inhibitor in radiation protection of
hematopoietic system. Aim 3 is to define the role of Lxn suppression in rejuvenating old HSCs. Findings will
advance our knowledge of novel mechanisms how Lxn regulates stress hematopoiesis. Results will provide a
compelling starting point and lay grounds for the novel drug discovery by targeting Lxn, which will benefit patients
subject to radiation treatment and old people with dysfunctional HSC and immune aging.

## Key facts

- **NIH application ID:** 10879150
- **Project number:** 5R01HL124015-09
- **Recipient organization:** NEW YORK BLOOD CENTER
- **Principal Investigator:** Ying Liang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $427,000
- **Award type:** 5
- **Project period:** 2023-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879150

## Citation

> US National Institutes of Health, RePORTER application 10879150, Latexin function in the maintenance and regeneration of the hematopoietic system (5R01HL124015-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10879150. Licensed CC0.

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