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Understanding the link between infection and rejection in kidney transplant recipients: Defining mechanisms of BK Polyomavirus reactivation and heterologous immunity

Award Number: K08AI202270
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/02/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Understanding the link between infection and rejection in kidney transplant recipients: Defining mechanisms of BK Polyomavirus reactivation and heterologous immunity - Project Summary/Abstract BK polyomavirus (BKPyV) reactivation is a leading cause of allograft injury and loss in kidney transplant recipients. Current approaches rely on reactive monitoring and reduction of immunosuppression after BKPyV is detected, yet these strategies can precipitate allosensitization and rejection. There is an urgent need to understand the mechanisms of BKpyV-specific cellular immunity in order to identify patients at highest risk for BKPyV reactivation before transplantation, thus enabling individualized immunosuppressive strategies and targeted monitoring. The overall objective of this proposal is to characterize features of the pre-transplant T cell repertoire that predict BKPyV reactivation and subsequent allograft rejection. Our central hypothesis is that quantitative and qualitative elements of the T cell repertoire—independent of immunosuppression intensity— differentiate recipients who experience BKPyV reactivation and allosensitization from those who do not. The rationale for this project is that definition of host cellular immune mechanisms underlying BKpyV reactivation and allosensitization can be leveraged to risk-stratify kidney transplant recipients. The central hypothesis will be tested by pursuing two specific aims: 1) Define phenotypic and transcriptional features of BKPyV-specific T cells to identify immune correlates and cellular mechanisms of viral reactivation and 2) assess heterologous immunity between BKPyV-specific memory and alloreactive T cells. These aims will be accomplished by means of structured mentorship wherein the applicant will establish expertise in immunologic laboratory methods under the guidance of established investigators and obtain a skillset in advanced transplant and computational immunology through structured coursework. The research proposed in this application is innovative in that novel methods such as single cell transcriptomics and T cell receptor sequencing will be applied to investigate mechanisms of BKpyV reactivation and cross-reactivity with Human Leukocyte Antigens (HLA). The proposed research is significant because it is expected to yield a mechanistic framework for BKPyV immune risk classification that incorporates T cell subset composition, transcriptional signatures, and HLA presentation capacity. This work will lay the foundation for the applicant to lead an R01 proposal studying how a biomarker- guided approach to immunosuppression can reduce infectious complications and mitigate alloimmune injury. Successful completion will equip the applicant with the knowledge and skillset to develop a niche as a kidney transplant clinician-scientist prepared to transition to an independent investigator.


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 = $171,796 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	9/2/2026	NEW	$171,796
														Subtotal = $171,796

Grand Total All Awards = $171,796

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Understanding the link between infection and rejection in kidney transplant recipients: Defining mechanisms of BK Polyomavirus reactivation and heterologous immunity

Award Number: K08AI202270

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/02/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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