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Immuno-Metabolic Drivers of Chronic Rejection after Lung Transplant

Award Number: K08HL185919
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Immuno-Metabolic Drivers of Chronic Rejection after Lung Transplant - PROJECT SUMMARY/ABSTRACT: Lung transplantation is a life-saving treatment for patients with end-stage lung disease, but the survival outcomes are severely limited due to the development of chronic rejection. Bronchiolitis obliterans syndrome (BOS) is a form of chronic rejection that is the major cause of death one-year after lung transplant and for which there are no effective therapies because we do not yet understand the mechanistic drivers. To provide further insights into these mechanisms and guide developing therapies, the PI has established a mouse model of lung transplantation with accelerated BOS development due to deficiency of an autophagy-related protein ATG16l1 in recipient monocyte-derived antigen presenting cells (Mo-APCS). This model was developed after the clinical observation that lung transplant patients with a hypofunctioning ATG16L1 variant are at significant risk for early BOS development. The PI’s preliminary data demonstrates that ATG16L1-deficient Mo-APCs undergo metabolic adaptation to increased glycolytic inflammatory responses with enhanced IL-1β and T cell alloimmune responses. In this proposal, the PI addresses the hypothesis that ATG16l1-deficient Mo-APCs drive BOS through this enhanced glycolytic and inflammatory IL-1β signaling by determining 1) if targeted Mo- APC inhibition of glycolysis using targeted delivery methods prevents BOS development, 2) identifying contributing metabolic pathways using metabolomic-transcriptomic profiling, and 3) determining the contribution of the IL-1β inflammatory response to BOS using pharmacologic and genetic inhibition strategies. The PI is an early career lung transplant physician scientist faculty at Washington University in Saint Louis (WashU) where she completed pulmonary and critical care fellowship. She is well-trained with subspecialty focus on the management of lung transplant patients and several years of mentored research in lung transplant immunology in this collaborative and multi-disciplinary environment with extensive facilities and resources. Through the proposed research and career plan, the PI will build on prior experience and fill training gaps to acquire the tools for independent investigation in lung transplant immunometabolism and targeted drug development. Specific objectives include didactive and technical training in 1) metabolism, immunometabolism, and metabolic profiling, 2) targeted drug delivery and 3) expertise in analysis with bioinformatics. The chosen mentor and advisors are renowned experts in these fields and have notable track records of training mentees into independent investigators. Designated benchmarks include 1) oral research presentations at national conferences, 2) refining manuscript and grant-writing skills through publications and grant submissions, 3) developing mentorship and leadership skills while establishing independent laboratory and personnel. In alignment with the NHLBI mission, at the conclusion of this award the PI will have the tools to be an independent physician scientist with expertise in immunometabolism and contributing to targeted drug developments to attenuate rejection to improve the survival of lung transplant patients.


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 = $169,140 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Lung Diseases Research	000	1	6/23/2026	NEW	$169,140
														Subtotal = $169,140

Grand Total All Awards = $169,140

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Immuno-Metabolic Drivers of Chronic Rejection after Lung Transplant

Award Number: K08HL185919

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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