# Yale Murine-TMC on Immune Cell Senescence Derived Inflammation

> **NIH NIH U54** · YALE UNIVERSITY · 2023 · $1,651,334

## Abstract

SUMMARY
Yale-murine TMC (mTMC), through application of high-content and high throughput single-cell and spatial omics
technologies, we aim to accelerate the discovery of senescent biomarkers, apply them to mouse models, and
generate hypotheses to test mechanisms of organismal aging. Our proposed unbiased analyses will also answer
the question whether senescent cells (stromal or hematopoietic lineage) exist in sufficient quantities to alter the
inflammatory landscape and biology. Yale-mTMC will use lineage-marked mouse to classify types or subtypes
of senescent cells, their spatial heterogeneity and how these cells impact the tissue environments. Yale-mTMC
will assemble 1) a multidisciplinary team to generate the molecular and cellular maps of cellular senescence in
Thymus, Bone marrow, Spleen, PBMCs, Mesenteric and Inguinal adipose tissue. 2) develop and deploy a suite
of high-resolution, high-content and high throughput single-cell and spatial omics technologies to characterize
these specimens and 3) perform integrated informatics to identify biomarkers of senescent cell heterogeneity
and to construct comprehensive molecular and cellular maps of cellular senescence and including an i.v CD45
antibody labeling/sorting approach to study tissue resident immune cells in non-lymphoid tissues. We will utilize
the analysis platforms established through the Yale human TMC to enable cross-species verification of
biomarkers. Three major biological analysis pipelines are: (A) Multiplex Imaging (MI) including CODEX, IMC,
and SMI, complemented by 3D light sheet microscopy of cleared tissues, (B) Single Cell Analysis (SCA) including
scCITE-seq for protein and mRNA profiling, CyTOF for high-plex immunophenotyping, and single-cell protein
secretome profiling to measure SASP heterogeneity, and (C) Spatial Multi-Omics Sequencing (SMOS) using
DBiT-based spatial-CITE-seq for spatially resolved proteo-transcriptomic mapping at genome scale. The
combination of these pipelines allows for highly sensitive and single-cell resolution mapping of senescent cells
and associated tissue environments. Yale-mTMC aims to assemble a multidisciplinary team led by PI: Dixit
(Director, Yale Center for Research on Aging), and MPI: Montgomery (Immunologist, Associate Dean for
scientific affairs) with Core Leads Dr. Fan (Bioengineer), Dr. Kluger (informatics and data analytics) and Key
personnel Dr. Booth (mouse pathologist), Dr. Lucas, Haberman (Immunologists, expert in pet store mouse model,
imaging) with IAB composed of scientific leaders Drs. Medzhitov, Iwasaki and Ruddle. We have experience in
management of large, multi-component programs and prior experience with generating significant high-quality
imaging and omics data as part of a consortium. A dedicated program manager will manage and coordinate all
activities across the center and with the SenNet consortium. Complementary and multidisciplinary scientific
expertise of the team will translate into the collective capability of t...

## Key facts

- **NIH application ID:** 10675111
- **Project number:** 5U54AG079759-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** VISHWA DEEP DIXIT
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,651,334
- **Award type:** 5
- **Project period:** 2022-08-02 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10675111

## Citation

> US National Institutes of Health, RePORTER application 10675111, Yale Murine-TMC on Immune Cell Senescence Derived Inflammation (5U54AG079759-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10675111. Licensed CC0.

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