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Solute carrier proteins in efferocytosis and inflammation

Award Number: R01AI159551
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/25/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Solute carrier proteins in efferocytosis and inflammation - Abstract: SOLUTE CARRIER (SLC) PROTEINS IN EFFEROCYTOSIS AND INFLAMMATION: It is truly remarkable that our bodies turn over on average about one million cells every second of life. The cells that are turned over, predominantly by the process of apoptosis, include excess cells generated as part of normal development, used/aged cells, and damaged cells arising from disease or infections. The efficient removal of such apoptotic cells is important for ‘making space’ for replacement by living cells, preventing inflammation, maintaining the function of the tissue/organ, and in turn, a healthy organism. The efficient removal of the dying cells occurs via the process of ‘efferocytosis’, and is done by professional phagocytes (such as macrophages and immature dendritic cells) or neighboring cells (e.g. fibroblasts, epithelial cells) within a given tissue. Efferocytosis, which involves ligands on apoptotic cells and specific receptors on phagocytes, is very efficient, and actively anti-inflammatory. However, impaired clearance of apoptotic cells results in the accumulation of dead cells, and the resulting chronic inflammation linked to a number of pathological conditions such as atherosclerosis, lung inflammation, and inflammatory bowel diseases. While significant progress has been made in understanding apoptotic cell recognition and efferocytic uptake in recent years, significant gaps remain. Solute carrier (SLC) proteins are membrane proteins that selectively conduct ions, metabolites, and aminoacids across the plasma membrane, and specific internal cellular membranes. In the human genome, SLCs represent the second largest family (after the GPCRs), with ~400 SLC family members. Despite ~100 human diseases being linked to mutations in SLC genes, the SLC family is relatively understided, including in the immune system 7,8. This may in part be because the SLCs functionally characterized have often been in isolation, and not many SLCs are studied as part of a larger biological process. Recently, while studying phagocytes taking up apoptotic cells, we unexpectedly came across a coordinated regulation of >30 members of the Slc gene family (Morioka et al., Nature 2018; Perry et al, Nature Cell Biol., 2019). This proposal tests the hypothesis that SLC proteins can play key roles in different phases of efferocytosis, and that sequential use of specific SLCs during efferocytosis facilitates communication between phagocytes contributes to maintaining an anti-inflammatory state within tissues.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $559,030 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	6	1/9/2025	NON-COMPETING CONTINUATION	$559,030
														Subtotal = $559,030

Issue Date FY: 2024 ( Subtotal = $576,319 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	5	12/14/2023	NON-COMPETING CONTINUATION	$518,687
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	001	5	5/20/2024	NON-COMPETING CONTINUATION	$57,632
														Subtotal = $576,319

Issue Date FY: 2023 ( Subtotal = $580,025 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	4	12/26/2022	NON-COMPETING CONTINUATION	$580,025
														Subtotal = $580,025

Issue Date FY: 2022 ( Subtotal = $593,695 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	004	2	8/29/2022	NON-COMPETING CONTINUATION	-$9,964
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	2	2/25/2022	NON-COMPETING CONTINUATION	-$583,731
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	005	3	8/29/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$328,140
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	002	3	2/28/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$583,731
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	2	12/15/2021	NON-COMPETING CONTINUATION	$593,695
2022	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	003	1	8/29/2022	NEW	-$318,176
														Subtotal = $593,695

Issue Date FY: 2021 ( Subtotal = $593,695 )
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	1	1/22/2021	NEW	$593,695
														Subtotal = $593,695

Grand Total All Awards = $2,902,764

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Solute carrier proteins in efferocytosis and inflammation

Award Number: R01AI159551

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/25/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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