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The Fibrosis-Immunity Interface in Corneal Transplantation

Award Number: K08EY031759
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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The Fibrosis-Immunity Interface in Corneal Transplantation - PROJECT SUMMARY/ABSTRACT The present proposal is a comprehensive five-year training program for the development of an academic career focused on understanding the relationship between T cell immunity and fibrosis in the cornea. I have a strong research background in transplantation immunology and sub-specialty ophthalmology training in cornea, with a clinical interest in corneal fibrosis. As an Advanced Clinical and Research Cornea Fellow at Mass. Eye and Ear and Harvard Medical School, I have continued my work in corneal transplantation immunology, demonstrating the presence of fibrosis in T cell-mediated immune rejection of corneal transplants. Our preliminary data suggest that in corneal transplantation, T cells play a direct role in promoting myofibroblast formation and fibrosis, and that myofibroblasts are in turn capable of regulating alloreactive T cell function. This data has laid the foundation for the current research proposal in which we will investigate the fibrosis-immunity interface in corneal transplantation. In Specific Aim 1 we will define the critical mechanisms by which effector T cells promote fibrosis and evaluate whether modulation of these mechanisms can prevent fibrosis and transplant failure in vivo. In Specific Aim 2 we will define the critical mechanisms by which myofibroblasts suppress effector T cells to restore immune homeostasis. The goal of the proposed research is to investigate these fundamental mechanisms and ultimately develop novel therapeutic strategies for the prevention of graft fibrosis and suppression of T cell immunity in organ transplantation. Dr. Reza Dana, a world expert in corneal immunology with a long track-record of fostering the career development of clinician-scientists will serve as my primary mentor, and I will additionally have the support of an advisory team composed of independent NIH-funded scientists, each with extensive experience in mentoring young researchers. The proposed research and career development programming will take place at the Schepens Eye Research Institute/Massachusetts Eye and Ear Infirmary and Harvard Medical School, and I will have full access to the significant resources of these institutions. I am committed to a career as a clinician-scientist, with the over-arching goal being to translate my basic science investigations into novel approaches for addressing the unmet needs of patients. The K08 grant proposal detailed here addresses an important and previously unexplored area of corneal pathophysiology while simultaneously providing me the mentorship, resources and academic foundation needed to become an independent clinician-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 = $0 )
2026	2024	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Vision Research	000	5	1/6/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $238,682 )
2024	2024	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Vision Research	000	5	7/12/2024	NON-COMPETING CONTINUATION	$238,682
														Subtotal = $238,682

Issue Date FY: 2023 ( Subtotal = $238,682 )
2023	2023	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Vision Research	000	4	6/8/2023	NON-COMPETING CONTINUATION	$238,682
														Subtotal = $238,682

Issue Date FY: 2022 ( Subtotal = $238,682 )
2022	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Vision Research	000	3	5/27/2022	NON-COMPETING CONTINUATION	$238,682
														Subtotal = $238,682

Issue Date FY: 2021 ( Subtotal = $238,682 )
2021	2021	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Vision Research	000	2	6/24/2021	NON-COMPETING CONTINUATION	$238,682
														Subtotal = $238,682

Issue Date FY: 2020 ( Subtotal = $238,682 )
2020	2020	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Vision Research	000	1	8/14/2020	NEW	$238,682
														Subtotal = $238,682

Grand Total All Awards = $1,193,410

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The Fibrosis-Immunity Interface in Corneal Transplantation

Award Number: K08EY031759

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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