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Differentiation and Function of Monocytes and Macrophages

Award Number: R37AI049653
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: 09/15/2011
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Differentiation and Function of Monocytes and Macrophages - Resident MΦs naturally reside freely floating in peritoneal fluid. To counteract the problem that phagocytosis of cargo is inefficient in fluid, peritoneal MΦs produce Factor V to raise its local levels and facilitate formation of interstitial clots upon induction of inflammation. The clots in turn bring MΦs and microbes out of the fluid phase and into a 3-D environment together. This clotting reaction operates with induced MΦ adhesion onto mesothelial membranes to collectively account for the classical MΦ disappearance reaction (MDR). MDR in the peritoneum may also require inflammasome activation, which may then lead to cell death that accounts for an extended period of MΦ disappearance. Indeed, when the stimulus inciting the MDR is robust, Factor V+ resident MΦs disappear for several weeks, likely leaving the peritoneal cavity susceptible to future infectious and noninfectious threats for rather long durations. We will study possible links between death and coagulation and use lineage tracing models to determine how resident MΦs repopulate. Furthermore, we will investigate the idea that the peritoneal cavity is left susceptible to immunological challenges during the long duration of MΦ loss following MDR. A prolonged period of MΦ loss following a robust MDR may leave the body cavity vulnerable to infection. It may also promote progression of other diseases associated with altered immunity, like cancers. In particular, ovarian cancer is associated with the peritoneal cavity, where it often metastasizes and expands. Human ovarian cancers are considered one of the most procoagulant tumors. If human counterparts to the Factor V+ MΦs exist, which we will study herein, such cells might limit tumor expansion clinically, as observed in mice. Overall, we will test the hypothesis that Factor V+ resident peritoneal macrophages protect the peritoneal cavity from microbial pathogens but also against ovarian tumors and that the procoagulant activity of these macrophages, if linked to MDR by a microbial or inflammatory trigger, may set up a state of enhanced susceptibility to tumor growth due to loss of tumor-restricting MΦs.


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 = $393,750 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	25	9/30/2025	NON-COMPETING CONTINUATION	$0
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	25	1/14/2025	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2024 ( Subtotal = $393,750 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	24	10/31/2023	NON-COMPETING CONTINUATION	$354,375
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	001	24	5/14/2024	NON-COMPETING CONTINUATION	$39,375
														Subtotal = $393,750

Issue Date FY: 2023 ( Subtotal = $393,750 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	23	11/10/2022	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2022 ( Subtotal = $390,051 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	22	11/5/2021	NON-COMPETING CONTINUATION	$393,750
2022	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	20	10/14/2021	SUPPLEMENT FOR EXPANSION	-$3,699
														Subtotal = $390,051

Issue Date FY: 2021 ( Subtotal = $393,750 )
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	002	21	8/10/2021	EXTENSION WITH OR WITHOUT FUNDS	$8,683
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	21	11/26/2020	EXTENSION WITH OR WITHOUT FUNDS	$393,750
2021	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	006	20	9/28/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	005	20	9/24/2021	SUPPLEMENT FOR EXPANSION	$12,415
2021	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	003	20	8/10/2021	SUPPLEMENT FOR EXPANSION	-$8,683
2021	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	20	4/30/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	004	20	8/10/2021	SUPPLEMENT FOR EXPANSION	-$12,415
														Subtotal = $393,750

Issue Date FY: 2020 ( Subtotal = $604,111 )
2020	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	20	11/26/2019	NON-COMPETING CONTINUATION	$381,250
2020	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	003	20	6/19/2020	SUPPLEMENT FOR EXPANSION	$164,107
2020	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	002	20	4/29/2020	SUPPLEMENT FOR EXPANSION	$0
2020	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	20	4/27/2020	SUPPLEMENT FOR EXPANSION	$58,754
														Subtotal = $604,111

Issue Date FY: 2019 ( Subtotal = $381,250 )
2019	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	19	11/20/2018	NON-COMPETING CONTINUATION	$381,250
2019	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	19	5/22/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $381,250

Issue Date FY: 2018 ( Subtotal = $381,250 )
2018	2018	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	18	11/15/2017	NON-COMPETING CONTINUATION	$381,250
														Subtotal = $381,250

Issue Date FY: 2017 ( Subtotal = $536,250 )
2017	2017	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	17	8/16/2017	NON-COMPETING CONTINUATION	$155,000
2017	2017	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	17	11/9/2016	NON-COMPETING CONTINUATION	$381,250
														Subtotal = $536,250

Issue Date FY: 2016 ( Subtotal = $381,250 )
2016	2016	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	16	11/26/2015	COMPETING CONTINUATION	$381,250
														Subtotal = $381,250

Grand Total All Awards = $4,249,162

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Differentiation and Function of Monocytes and Macrophages

Award Number: R37AI049653

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: 09/15/2011

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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