# Mechanisms regulating apoptotic cell clearance in health and disease

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2021 · $122,688

## Abstract

Abstract

It is truly remarkable that our bodies turn over/recycle about one million cells every second of life (0.1%-
0.4% of body mass daily). The cells that are turned over can include excess cells generated as part of normal
development, homeostasis, used/aged cells, and damaged cells that arise from disease or infections. Although
there are many forms of cell death, a large majority of these cells die via apoptosis. Professional phagocytes
(such as macrophages and immature dendritic cells), or neighboring cells (fibroblasts and epithelial cells), as
well as specialized phagocytes (such as Sertoli cells) mediate the removal of the dying cells. The prompt and
efficient removal of cells is important at several levels, including `making space' for replacement by living
cells, preventing inflammation, maintaining the function of the tissue/organ, and in turn, a healthy
organism3. When apoptotic cells fail to be cleared promptly, this can lead to secondary necrosis and the
release of their intracellular contents from uncleared cells, and a predilection to autoimmunity,
atherosclerosis, and certain neurological pathologies. Moreover, how apoptotic cells that are often seen in
actively growing tumors and after chemo-, radiation-, or immuno-therapies has relevance to
immunosuppression or immune responses to the tumor derived cells. While the field of apoptotic cell
clearance is exciting ,and studies to date have identified some of the basic steps, there are still large and
significant gaps in our knowledge. Some of these include: why do we have so many engulfment receptors on
phagocytes, are there unique signals via these receptors, can we possibly dial up the capacity for engulfment
to dampen inflammation in specific disease conditions, and how does a phagocyte (such as a macrophage)
take up so much excess `cargo' and still maintain its normal metabolomics, etc. While these are large
questions unto itself, these are also inter-related, and over the past 15 years, our laboratory has obtained and
used different tools to address these questions, and we have also significantly contributed to moving this field
in several exciting directions. The overall goal of this MIRA project is to take novel approaches that will help
us better define the key steps/molecular features of the apoptotic cell clearance process and also attempt to
modulate the engulfment machinery for possible therapeutic benefits in disease models.

## Key facts

- **NIH application ID:** 10159281
- **Project number:** 5R35GM122542-05
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Kodi S Ravichandran
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $122,688
- **Award type:** 5
- **Project period:** 2017-06-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159281

## Citation

> US National Institutes of Health, RePORTER application 10159281, Mechanisms regulating apoptotic cell clearance in health and disease (5R35GM122542-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10159281. Licensed CC0.

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