U54AG079759
Cooperative Agreement
Overview
Grant Description
Yale Murine-TMC on Immune Cell Senescence Derived Inflammation - Summary
Yale-Murine TMC (MTMC), through the application of high-content and high throughput single-cell and spatial omics technologies, aims 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.
3) Perform integrated informatics to identify biomarkers of senescent cell heterogeneity and to construct comprehensive molecular and cellular maps of cellular senescence, 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.
(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 the 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 the TMC to foster integration of multi-dimensional, multiparameter data generation and coordination with SENNET and other TMCs for greater impact.
Yale-Murine TMC (MTMC), through the application of high-content and high throughput single-cell and spatial omics technologies, aims 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.
3) Perform integrated informatics to identify biomarkers of senescent cell heterogeneity and to construct comprehensive molecular and cellular maps of cellular senescence, 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.
(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 the 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 the TMC to foster integration of multi-dimensional, multiparameter data generation and coordination with SENNET and other TMCs for greater impact.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding Agency
Place of Performance
Connecticut
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 293% from $1,664,871 to $6,545,018.
Yale Univ was awarded
Yale Murine-TMC on Immune Cell Senescence Derived Inflammation
Cooperative Agreement U54AG079759
worth $6,545,018
from the National Institute of Allergy and Infectious Diseases in August 2022 with work to be completed primarily in Connecticut United States.
The grant
has a duration of 4 years and
was awarded through assistance program 93.310 Trans-NIH Research Support.
The Cooperative Agreement was awarded through grant opportunity Cellular Senescence Network: Murine Tissue Mapping Centers (U54 - Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 8/20/25
Period of Performance
8/2/22
Start Date
7/31/26
End Date
Funding Split
$6.5M
Federal Obligation
$0.0
Non-Federal Obligation
$6.5M
Total Obligated
Activity Timeline
Transaction History
Modifications to U54AG079759
Additional Detail
Award ID FAIN
U54AG079759
SAI Number
U54AG079759-958741920
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Private Institution Of Higher Education
Awarding Office
75NN00 NIH National Insitute on Aging
Funding Office
75NA00 NIH OFFICE OF THE DIRECTOR
Awardee UEI
FL6GV84CKN57
Awardee CAGE
4B992
Performance District
CT-90
Senators
Richard Blumenthal
Christopher Murphy
Christopher Murphy
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| Office of the Director, National Institutes of Health, Health and Human Services (075-0846) | Health research and training | Grants, subsidies, and contributions (41.0) | $3,316,205 | 100% |
Modified: 8/20/25