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MAP2K2 in influenza virus-induced acute lung injury and resolution

Award Number: K01OD038415
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2030

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MAP2K2 in influenza virus-induced acute lung injury and resolution - PROJECT SUMMARY/ABSTRACT The purpose of this K01 SERCA application is to provide the protected research time and mentorship necessary for Dr. Jourdan Brune, DVM, PhD, DACLAM, to become an independent investigator. Dr. Brune is a veterinarian with a strong background in comparative medicine, influenza virus-induced lung injury, and preclinical animal models, making her uniquely qualified for a career in biomedical research. Under the guidance of her mentor, Dr. Anne Manicone, and an interdisciplinary advisory committee, the training and aims outlined in this proposal will allow Dr. Brune to expand her knowledge in host responses to viral pneumonia and establish a solid foundation for her own independent research program focused on host responses to emerging and re-emerging viral respiratory pathogens. The University of Washington will provide the interactive and collaborative environment necessary to support her transition to independence. Understanding host factors that exacerbate lung inflammation and injury initiated by viral pathogens, such as influenza A virus, is essential to developing new therapeutic strategies. The mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated protein kinase (ERK) signaling cascade is a highly conserved pathway that is activated during lung injury in both rodents and humans. Recently, a genetic polymorphism in Map2k2 (MEK2) was associated with death in acute respiratory distress syndrome, thereby identifying MEK2 as a potential host-directed therapeutic target and emphasizing the significance of the proposed research to acute lung injury (ALI). To test my hypothesis that MEK2 impairs ALI resolution in viral pneumonia, I exposed wild- type and MEK2-/- mice to influenza infection with A/PR/8/34. At a high dose, I observed increased survival in MEK2-/- mice. Using a lower dose to allow all mice to survive, initial weight loss and inflammatory responses were similar, but at later times, MEK2-/- mice had faster recovery of body weight, better clinical scores, and reduced monocyte and lymphocyte numbers in the lung. Importantly, viral proliferation and clearance were similar in both genotypes, suggesting that MEK2 is critical for regulating the adaptive and recovery phases of influenza infection. I have also found increased MEK1/ERK activation in MEK2-/- mice. Based on these findings,I hypothesize that MEK2 perpetuates detrimental immunopathology during viral pneumonia, and it may do so via MEK1 deactivation. Using novel preclinical transgenic rodent models, this proposal aims to understand how MEK2 contributes to immunopathology and lung injury during IAV infection and provide mechanistic insight regarding MEK2’s role in regulating MEK1 activation. The completion of the proposed studies represents an important step in understanding host signaling pathways that exacerbate lung injury and will provide Dr. Brune with the critical skills necessary to become an R01-funded translational veterinary scientist.


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 = $122,769 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Research Infrastructure Programs	000	1	6/24/2026	NEW	$122,769
														Subtotal = $122,769

Grand Total All Awards = $122,769

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MAP2K2 in influenza virus-induced acute lung injury and resolution

Award Number: K01OD038415

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2030

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