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NLRP10 Inflamasome in Gram-positive Sepsis

Award Number: F31HL168986
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2025
AWARD TERMINATION DATE: 06/16/2025

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NLRP10 Inflamasome in Gram-positive Sepsis - ABSTRACT Sepsis is an important cause of mortality, morbidity, and health care expenditures in immunocompetent and immunosuppressed populations globally. Sepsis can lead to tissue injury, and eventually results in tissue dysfunction and subsequent failure. Lower respiratory tract infections are a prominent inducer of septicemia/sepsis (aka pneumonia-derived sepsis). Antibiotics are common treatments for these infections. However, the use of these drugs will apply pressure on the bacterium to gain antibiotic resistance. Therefore, there is a strong need for to broaden our knowledge and the development of new methods of treatment. In this regard, vigorous recruitment of neutrophils to clear bacteria is a key innate immune mechanism. Paradoxically, uncontrolled neutrophil leads to extensive tissue damage and organ failure. In addition to membrane bound Toll-Like Receptors (TLRs), cytosolic NOD-like receptors (NLRs) serve as critical molecules of innate immunity in pathological settings. Selective NLRs termed “Inflammasomes” which are key receptors and/or sensors in innate immunity that induce inflammation in response to invading pathogens. Among inflammasomes, NLR family pyrin domain containing 3 (NLRP3) is the most studied and has been shown to play an important role during bacterial respiratory infections. However, the role of NACHT, leucine-rich repeat (LRR), and PYD containing protein 10 (NLRP10) in Gram-positive pneumonia remains to be delineated because this is a recently identified inflammasome and does not have a leucine rich domain (LRR). Our lab preliminary data demonstrated that (1) pneumonic human lungs show upregulated NLRP10 expression in macrophages, neutrophils, and epithelial cells; (2) mouse lungs display upregulation of NLRP10 in myeloid and structural cells following sepsis; and (3) NLRP10 knockout (KO) mice show reduced bacterial burden in the lungs and decreased bacterial dissemination to extrapulmonary organs following Gram-positive infection. Taken together, this preliminary data led to the hypothesis that the NLRP10 inflammasome is a central regulator of organ damage in Gram-positive pneumonia-induced sepsis. Two related but independent aims have been proposed: (1) To delineate the mechanisms by which NLRP10 inflammasome regulates pathogen clearance during Gram-positive infection; and (2) To determine if ablation of NLRP10 inflammasome can modulate alveolar macrophage, neutrophil, and alveolar type II epithelial cell function in Gram-positive infection. The proposed studies will uncover mechanistic insights into the role of NLRP10 on pneumonia- induced sepsis. The National Research Service Award will enable the PI to gain mentored research training from a more experienced faculty along with an outstanding dissertation committee in order to obtain an academic position.


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: 2026 ( Subtotal = -$21 )
2026	2024	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Lung Diseases Research	000	2	4/22/2026	TERMINATION	-$21
														Subtotal = -$21

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Lung Diseases Research	000	2	6/16/2025	TERMINATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $43,416 )
2024	2024	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Lung Diseases Research	000	2	6/10/2024	NON-COMPETING CONTINUATION	$43,416
														Subtotal = $43,416

Issue Date FY: 2023 ( Subtotal = $42,136 )
2023	2023	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Lung Diseases Research	001	1	6/28/2023	NEW	$0
2023	2023	LOUISIANA STATE UNIVERSITY	202 HIMES HALL	BATON ROUGE	LA	70803	EAST BATON ROUGE	USA	Lung Diseases Research	000	1	6/28/2023	NEW	$42,136
														Subtotal = $42,136

Grand Total All Awards = $85,531

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NLRP10 Inflamasome in Gram-positive Sepsis

Award Number: F31HL168986

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2025

AWARD TERMINATION DATE: 06/16/2025

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