# Complement Dependent Inflammation and Murine Heart Transplant Rejection

> **NIH NIH K08** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $190,339

## Abstract

Project Summary/Abstract
Research Summary: Long-term post-transplant outcomes remain suboptimal, especially for recipients
of deceased donor organs. Building upon previous studies, our preliminary data from a murine heart
transplant model implicate peri-transplant complement-mediated ischemia reperfusion (IR) injury and
inflammation as a central mediator of increased alloimmunity and late graft failure/dysfunction. In this
project we will study the mechanisms and effects of complement activation on IR-associated
inflammation (Aim 1) and the mechanisms linking increased IR-induced complement-dependent
inflammation to late post-transplant allospecific immunity and outcomes (Aim 2). These aims will test
our central hypothesis that IR-injury induced inflammation is dependent upon recipient mannose
binding lectin-dependent complement activation, that inflammation induces greater recipient APC
activation/donor antigen acquisition, and that these primed APCs then foster a stronger adaptive anti-
donor T cell response leading to graft rejection. The specific findings have the potential to identify
novel therapeutic targets that can be translated to human trials to improve transplant outcomes.
Environment: Both the Icahn School of Medicine at Mount Sinai and Division of Nephrology are firmly
committed to junior faculty career development. Dr. Peter Heeger (mentor) is an established expert in
the field of complement immunology and transplant research with a strong record of developing junior
faculty into independent researchers. Candidate Training: The primary objective of this application is
to support Dr. Nicholas Chun's career development into an independent researcher scientist in the field
of complement immunobiology and human disease. Dr. Chun's proposed training activities are in four
broad non-mutually exclusive areas: 1) Enhancement of fundamental knowledge (e.g. immunology,
complement, and exosome biology); 2) Scientific Communication (e.g. manuscript/grant writing,
presentation skills); 3) Practical skills (e.g. statistical analysis, large data set analysis, advanced
imaging); 4) Managerial skills (e.g. lab finances, personnel administration). The general approaches
and skills outlined during this award will form the basis for future research.
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## Key facts

- **NIH application ID:** 9915875
- **Project number:** 5K08AI135101-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Nicholas Chun
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,339
- **Award type:** 5
- **Project period:** 2018-05-03 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9915875

## Citation

> US National Institutes of Health, RePORTER application 9915875, Complement Dependent Inflammation and Murine Heart Transplant Rejection (5K08AI135101-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9915875. Licensed CC0.

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