# Plasma Cells in Health and Disease

> **NIH NIH P01** · EMORY UNIVERSITY · 2024 · $2,686,806

## Abstract

Antibody secreting cells (ASC) are responsible for both protective and pathogenic responses
through the function of populations endowed with different function and longevity. Hence, major
unmet need in human health and disease is a deep understanding of the processes that underlie
ASC generation from different B cell precursors through separate differentiation pathways; the
metabolic, transcriptional and epigenetic programs that underpin these processes, thereby
promoting the generation of diverse ASC populations of different longevity and function; and how
these processes may be subverted in SLE leading to expansion of pathogenic autoreactive
plasma cells. Proper ASC function and dysregulation respectively provide protection in
vaccination and infection and mediate multiple diseases including SLE and other autoimmune
conditions, allergic reactions and transplant rejection. Thus, understanding the processes that
regulate differentiation and survival of protective ASC while avoiding the accumulation of
pathogenic ones is essential for our ability to improve vaccination and treat multiple antibody-
mediated diseases.
Over the previous cycle, despite the severe disruption caused by the COVID-19 pandemic for
over a year, our work has contributed major progress in these areas that provides the foundation
for this renewal application. Combined, our work will address the following concepts: Theme 1 -
ASC heterogeneity in human healthy and autoimmune responses; Theme 2 - Molecular and
epigenetic regulation of PC development and survival; Theme 3 - Metabolic regulation of ASC
differentiation, function and survival; Theme 4: Microenvironment regulation of ASC formation,
survival and function. These goals will be accomplished by highly interactive investigators through
the following Projects and cores:
Project 1. Epigenetic and metabolic mechanisms governing commitment to the long-lived
plasma cell pool (Lund, PI).
Project 2. Epigenetic programming of plasma cell heterogeneity and metabolism. (Boss, PI)
Project 3. Role of Cellular Senescence in long-lived plasma cell generation. (Lee, PI)
Project 4. Heterogeneity. Regulation and Function of Antibody-Secreting Cells in SLE (Sanz, PI)
Core A. Administrative Core (Sanz, PI)
Core B. Epigenomics, Bioinformatics, and Genome Engineering (Scharer, PI)

## Key facts

- **NIH application ID:** 10835936
- **Project number:** 5P01AI125180-08
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Ignacio E. Sanz
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,686,806
- **Award type:** 5
- **Project period:** 2016-06-25 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835936

## Citation

> US National Institutes of Health, RePORTER application 10835936, Plasma Cells in Health and Disease (5P01AI125180-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10835936. Licensed CC0.

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