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Targeting host nuclear receptors for the resolution of Staphylococcus aureus Skin Infections

Award Number: R21AI187620
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: 07/25/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Targeting host nuclear receptors for the resolution of Staphylococcus aureus Skin Infections - Methicillin-Resistant Staphylococcus aureus (MRSA) is a common cause of skin and soft tissue infections (SSTIs) in healthy patients. While usually self-resolving, prolonged MRSA SSTIs risk dissemination to other disease presentations including sepsis, endocarditis and osteomyelitis. Quick resolution of MRSA SSTIs reduces this risk. We have found that the two-phase host response to MRSA SSTIs can adequately resolve MRSA SSTIs. More importantly, the resolution phase is where the bacteria are cleared as opposed to the initial inflammatory phase. We have reported that PPAR is a critical regulator responsible for the switch from the inflammatory phase to the resolution phase. Treating animals with activators of PPAR can hasten the onset of the resolution phase and the clearance of the infection. This application seeks to solidify these observations and to define the signals that PPAR senses to become active and exploit these signals as topical treatment options. We further propose an exploratory aim in which we will document the macrophage populations and how they change over time using single cell RNA_Seq. We will see the dynamic switch from pro-inflammatory to efferocytotic macrophages and the transcriptional signatures associated with each phenotype. We will also be able to see how our treatment affects the dynamic macrophage populations during a MRSA SSTI.


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 = $437,250 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	1	7/28/2025	NEW	$437,250
														Subtotal = $437,250

Grand Total All Awards = $437,250

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Targeting host nuclear receptors for the resolution of Staphylococcus aureus Skin Infections

Award Number: R21AI187620

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: 07/25/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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