# Core C: Thymic and peripheral Aspects of T cell Aging and Rejuvenation

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2020 · $112,576

## Abstract

ABSTRACT
Using innovative forward-thinking mouse models and approaches, the Projects in this comprehensive
discovery-based Thymus Rejuvenation PPG seek to (i) identify mechanisms behind reduced thymic production
and impaired peripheral maintenance of T cells with aging and stress, and (ii) develop combined strategies to
ameliorate these defects and improve immune defense against infection and cancer in the elderly. Critical to
the translation potential of project-identified mechanisms, pathways and therapeutic targets in future programs,
is proof-of-concept verification of applicability of mouse targets/pathways to human thymus aging, and
centralized assessment of thymic function (i. e. sjTREC). To meet this need a central Human Target
Verification and Thymic Function Core (Core C) has been integrated into this Program Project. At the
center of the Core is the Duke Human Vaccine Institute (DHVI) Human Thymus Tissue Biobank, which
contains more than 900 healthy-donor human thymus tissues (ages 1 day to 80 years). The Thymus Biobank
consists of FFPE tissue blocks, snap-frozen frozen tissue chunks, and DMSO-cryopreserved thymocytes and
T cell depleted stroma. The Biobank has been maintained by the Core leader, Dr. Greg Sempowski, for 15+
years and has been extensively characterized by Dr. Sempowski and Core co-investigator/pathologist, Dr.
Laura Hale. Dr. Hale's immunohistochemical analysis and Dr. Sempowski's molecular analysis (i. e. gene
expression and TCR rearrangement) of tissues from the Biobank laid the foundation for our modern
understanding of changes in human thymus architecture and function across the lifespan. Core C will
accelerate proof-of-concept verification of project-identified mouse therapeutic targets/pathways in human
thymus aging/rejuvenation and independently monitor thymic output with three focused specific aims: (SA1)
Define and characterize age, sex and phenotypically applicable human thymus tissues panels to meet project-
specific translation verification needs. Provide central histologic and molecular analyses on tissue panels;
(SA2) provide centralized expert board-certified pathology support for human and mouse tissue staining,
scoring and analysis; and (SA3) provide standardized, quality-controlled assay support for mouse sjTREC
assays. Successful delivery of Core C services to Projects 1-4 and Core D will: (i) add considerable value to
this overall program, (ii) be a key component of overall program synergy, and most importantly, (iii) provide
critical proof-of-concept verification of applicability of mouse targets/pathways to human thymus
aging/rejuvenation to ameliorate age-associated immune deficiencies and improve immune defense against
infection and cancer in the elderly.

## Key facts

- **NIH application ID:** 9967946
- **Project number:** 5P01AG052359-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Gregory D Sempowski
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $112,576
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9967946

## Citation

> US National Institutes of Health, RePORTER application 9967946, Core C: Thymic and peripheral Aspects of T cell Aging and Rejuvenation (5P01AG052359-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9967946. Licensed CC0.

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