Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The Protective Role of Pulmonary Endothelial Cell Antigen Presentation in Sequential Influenza Infection

Award Number: F31HL186542
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/06/2026
PERIOD OF PERFORMANCE END DATE: 07/05/2029

Group Awards By:

View Award Description

The Protective Role of Pulmonary Endothelial Cell Antigen Presentation in Sequential Influenza Infection - PROJECT SUMMARY/ABSTRACT Influenza A virus (IAV) continues to pose a significant threat to global public health, affecting millions of people annually. Worryingly, the highly pathogenic avian influenza virus H5N1 has emerged as an additional threat, demonstrating cross-species transmission and human mortality in the USA. Patients infected with H5N1 are likely to have adaptive immunity induced by prior exposure of seasonal IAV. Therefore, understanding the mechanisms of immune protection conferred by prior infection against H5N1 is imperative. The major cause of IAV-induced mortality is acute respiratory distress syndrome (ARDS) or acute lung injury (ALI), characterized by extensive loss of lung vascular barrier function and excessive inflammation. In additional to their barrier function, the immunomodulatory role of endothelial cells (ECs) has recently gained recognition in fields such as cancer, transplantation, parasitic infections, etc. However, little is known about how EC immunomodulation influences T cell responses during IAV-induced adaptive memory formation. Our research indicates that pulmonary microvascular endothelial cells (PVECs) function as antigen-presenting cells that cross-present influenza antigens to lung-resident CD8+ T cells. Our preliminary data show that mice with a conditional endothelial-specific MHC-I knockout exhibit reduced populations of CD8+ resident memory T cells (TRM) and diminished cytotoxic potential during acute IAV infection. Moreover, the cross-presentation of PVECs to CD8+ T cells was further confirmed in vitro co-culturing system. In the context of sequential IAV infection, we hypothesize that H1N1- induced EC-medicated CD8+ T cell immune memory protects sequential H5N1 infection. To test this hypothesis, we aim to: (1) explore the protective role of EC-mediated CD8+ T cell memory and activation in sequential H1N1- H5N1 infection in Aim 1; and (2) characterize the impact of sequential H1N1 and H5N1 infection on pulmonary EC immunomodulation in Aim 2. This project will be conducted at the renowned University of Pittsburgh under the mentorship of Dr. Lianghui Zhang and Dr. John Alcorn. It includes a comprehensive predoctoral training plan to develop expertise in the immunopathology of IAV infections, master essential investigative techniques, and enhance scientific communication and independence. Ultimately, this research aims to characterize EC immunomodulation-based resistance to H5N1 and benefit the millions impacted by IAV annually. Successful completion of this project could lead to novel therapeutic strategies that bolster EC-mediated long-term T cell immunity, thereby reducing mortality and alleviating lung injury following highly pathogenic influenza infections. Upon completing this training, the applicant will be well-prepared to pursue his career goal: an innovative and independent scientist specializing in mechanism-based therapeutic development for respiratory viral lung injury.


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 = $50,114 )
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	000	1	7/6/2026	NEW	$50,114
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	001	1	7/6/2026	NEW	$0
														Subtotal = $50,114

Grand Total All Awards = $50,114

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The Protective Role of Pulmonary Endothelial Cell Antigen Presentation in Sequential Influenza Infection

Award Number: F31HL186542

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/06/2026

PERIOD OF PERFORMANCE END DATE: 07/05/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer