# Bio-Analysis-Core

> **NIH NIH U54** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $1,030,191

## Abstract

ABSTRACT
Biological Analysis Core. The cardiopulmonary system is a major inter-dependent organ system in the human
body, which has a major impact on overall life span and aging. Understanding the mechanisms that distinguish
beneficial from deleterious senescence and the heterogeneity underlying senescent cell states in this organ
system is critical. The overall aim of the Biological Analysis Core (BAC) is to generate a high-resolution map
of cellular senescence in lung and heart tissue across the lifespan, using state-of-the-art technologies, and
identify robust biomarkers of cellular senescence that will predict therapeutic responses to senolytics. We will
generate and refine endogenous signatures of cellular senescence at single cell resolution in healthy lung and
heart tissue employing comprehensive profiling of current markers of senescence using unbiased high-content
screening. We will apply a range of state-of-the-art, high-resolution, and high-throughput methods to calibrate,
validate, and produce precise mapping data of senescence. These will include multi-color flow cytometry, high
resolution imaging of cleared as well as native tissue, scRNASeq/snATAC/PIC-seq multi-omics, proteomics, and
spatial transcriptomics. We will interrogate 3D ex vivo human lung and heart tissue subjected to specific drivers
of senescence (e.g., DNA damage, telomere attrition) to define senescence heterogeneity and refine current
senescence signatures. Lung and heart PCTS will be subjected to defined senescence-inducing perturbations
to map the response of single cells in their natural 3D environment using omics analysis and 3D high-resolution
confocal time-lapse imaging for visualization, tracking, and tracing of senescence cells in their natural
environment ex vivo. Finally, we will define the senescence phenotype and function of primary senescent cells
sorted from human lung and heart tissue and will determine cell- and organ-specific responses to senolytics by
assessing their changes in senescence signatures and SASP biomarkers. These novel signatures and
biomarkers of senescence generated in the BAC will continuously feed into tissue mapping analysis and will
thereby refine the spatiotemporal mapping of cellular senescence by hierarchical clustering and deconvolution
using computational analysis and artificial intelligence approaches. This will allow us to map senescent cells at
unprecedent spatial resolution and 3D reconstruction across the lifespan and to generate a comprehensive and
in-depth Lung and Heart Senescence Map.

## Key facts

- **NIH application ID:** 10492702
- **Project number:** 5U54AG075931-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Melanie Koenigshoff
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,030,191
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492702

## Citation

> US National Institutes of Health, RePORTER application 10492702, Bio-Analysis-Core (5U54AG075931-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10492702. Licensed CC0.

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