# Characterizing the molecular signature of chronic graft-versus-host disease following hematopoietic stem cell transplantation

> **NIH NIH K23** · EMORY UNIVERSITY · 2021 · $63,500

## Abstract

Project Summary:
Allogeneic hematopoietic stem cell transplantation (HCT) is an effective treatment for hematological
malignancy, however it is associated with significant complications limiting its application. Chronic graft-versus-
host disease (CGVHD) is the leading cause of long-term morbidity and mortality following HCT and recent
advances have failed to make a significant impact on its frequency or severity. The mechanisms of the
development and evolution of CGVHD have not been clearly defined making the design of new therapeutic
approaches aimed at preventing or treating the disease challenging. Flow cytometry and gene expression
profiling have become valuable tools to interrogate complex disease states and define the molecular changes
that occur during the development of disease. Utilizing these approaches to identifying the mechanistic drivers
of CGVHD would aid significantly in our understanding of the disease and help elucidate targetable pathways
to alter its natural history.
To identify the mechanisms driving GVHD, our group has developed a systems biology approach that
combines flow cytometry with gene expression analysis. The proposed research project will apply these
supervised and unsupervised approaches to determine the molecular signature of T and B cells linked to the
development and evolution of CGVHD. The proposed work will utilize the highly curated biorepository of our
clinical trial. The randomized, placebo-controlled phase II clinical trial is investigating abatacept (CTLA4-Ig) as
a novel GVHD prevention agent and will provide detailed clinical data that will be linked to the biologic
samples. Aim 1 will seek to identify the T and B cell genes and pathways associated with the development and
evolution of CGVHD and determine if the molecular changes can be used to risk-stratify patients at day 100.
Aim 2 will seek to address the impact of abatacept on CGVHD by identifying the T and B cell genes and
pathways associated with CGVHD in abatacept treated patients and compare the associated molecular
changes to the changes that occur in patients with CGVHD not exposed to abatacept. Completion of these
aims will add significantly to our understanding of the development and evolution of CGHVD and hopefully
provide the data necessary to create a risk-adapted approach to CGVHD prevention. It will also provide insight
into the mechanism of action of abatacept and reveal the means of the breakthrough CGVHD that occurs.
Dr. Watkins has identified an exceptional mentoring team and in combination with his experience and career
development plan is poised to succeed with his proposed research plan. Dr. Watkins will benefit greatly from
the supportive research environment of Emory University and the formal training in clinical trial methodology
and bioinformatics will solidify his skills in clinical research. The structure and support provided by the K23 will
facilitate Dr. Watkins’ translation into a successful independent physician scien...

## Key facts

- **NIH application ID:** 10394036
- **Project number:** 3K23HL136900-04S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Benjamin Watkins
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $63,500
- **Award type:** 3
- **Project period:** 2017-05-01 → 2022-01-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10394036

## Citation

> US National Institutes of Health, RePORTER application 10394036, Characterizing the molecular signature of chronic graft-versus-host disease following hematopoietic stem cell transplantation (3K23HL136900-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10394036. Licensed CC0.

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