# Administrative Core

> **NIH NIH P01** · RESEARCH INST OF FOX CHASE CAN CTR · 2020 · $172,068

## Abstract

PROJECT SUMMARY/ABSTRACT
The primary role of the Administrative Core is to coordinate research activities among the 4 Project Sites and
Genomics Core. Biological research has moved well beyond the analysis of single genes or pathways.
Accordingly, this program seeks to use genome-wide analysis to gain insight into the way that differences in T
cell receptor (TCR) signal strength direct thymic progenitors to adopt the γδ fate, as well as how they might
influence effector fate specification. To do so, we have employed genomic analysis focused initially on the cellular
targets of E box DNA-binding proteins (E proteins), which regulate critical checkpoints in development of αβ and
γδ T cells. Our genome-wide analysis of E protein binding sites in the last funding cycle revealed a number of
critical E protein targets and cooperating transcription factors that are critical in adoption of the γδ T cell fate. We
now seek to leverage those findings through the Genomics Core to assess the function of those E protein
targets within our genome-wide E protein focused network and determine how they influence γδ lineage fate.
The program integrates the efforts of four leaders in γδ T cell development and E protein function. Project 1 will
explore the E protein targets, Tcf7 and long noncoding RNA (lncRNA) Gm15417, in orchestrating γδ lineage
commitment and adoption of the IL-17 producing effector fate. Project 2 will assess the role of E protein
regulated elements in controlling noncoding transcription from the TCRVδ element employed by innate-like
NKγδT cells and the TF Egr2, which plays a critical role in orchestrating NKγδ T cell development. Our program
has also discovered that particular E protein family members have specific, non-redundant roles in supporting
γδ T cell development and Project 3 will elucidate the mechanistic basis for their specific roles. Project 3 has
also developed a pluripotent stem cell (PSC)-based human γδ T cell development model that will enable us to
assess the human relevance of program findings made in animal models. Finally, Project 4 will evaluate the role
of an E protein controlled lncRNA, ThymoD, in regulating T lineage commitment and how its loss results in the
extinguishing of αβ fate potential in cells committed to the γδ fate. Specifically, Project 4 will also employ imaging
to visualize the effect of ThymoD on the kinetics of chromosome looping during γδ T cell development, which is
a critical regulator of gene expression. The Administrative Core will coordinate these activities by: 1) re-
establishing a management structure; 2) facilitating the distribution of reagents; and 3) coordinating scientific
interchanges between project sites and trainee visits to the Genomics Core, and as necessary other Program
Laboratories. Collectively, our program promises not only to reveal novel insights into the molecular control of
γδ T cell development, but will also equip a new cadre of scientists with the skills to apply integrate...

## Key facts

- **NIH application ID:** 9989055
- **Project number:** 5P01AI102853-07
- **Recipient organization:** RESEARCH INST OF FOX CHASE CAN CTR
- **Principal Investigator:** DAVID L. WIEST
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $172,068
- **Award type:** 5
- **Project period:** 2014-05-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989055

## Citation

> US National Institutes of Health, RePORTER application 9989055, Administrative Core (5P01AI102853-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989055. Licensed CC0.

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