# Role of Kidney-Draining Lymph Node in Crescentic Glomerulonephritis

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $168,489

## Abstract

Project Summary/Abstract
This proposal details a five-year research career development plan centered on the development of a platform
for the targeted delivery of immunosuppressive agents (ISAs) for crescentic glomerulonephritis (CGN) to the
kidney-draining lymph node (KLN), which can increase the efficacy and reduce the toxicity of the current
standard therapy for this condition. The candidate is an Instructor in the Department of Medicine at Harvard
Medical School (HMS) and Associate Physician in the Division of Renal Medicine at Brigham and Women's
Hospital (BWH). This proposal details a clear path to independence for the candidate through the guidance of
a multi-disciplinary group of scientists with complementary expertise and exemplary records of mentorship: (1)
Reza Abdi (Mentor), an NIH-funded transplant nephrologist at BWH who holds 2 R01 grants, (2) David Salant
(Advisor), a world-renowned physician-investigator in glomerular disease at Boston University, (3) Ulrich von
Andrian (Advisor), a preeminent lymph node immunologist at HMS, and (4) Jeffrey Karp (Advisor), an engineer
at HMS and BWH who conducts pioneering research in drug delivery. This guidance will be bolstered by
pursuit of coursework and acquisition of laboratory skills that are tailored to the candidate's career goals and
crucial for his successful transition to independence as a physician-scientist in the field of renal immunology.
The standard treatment for CGN, a rapidly progressive inflammatory condition that can lead to kidney failure
within days, involves the use of potent systemic ISAs that can cause severe side effects that may result in
death. Therefore, a pressing unmet clinical need exists for targeted immunosuppressive therapy for CGN, but
this remains an underexplored field of research. Fibroblastic reticular cells (FRCs) are resident stromal cells of
the lymph node (LN) that contribute actively to the propagation of an adaptive immune response. Preliminary
data from a first-author study published by the candidate indicates that the activity of FRCs in the KLN is
crucial to the propagation of the cell-mediated immune response in a mouse model of CGN known as
nephrotoxic serum nephritis (NTN). In addition, the candidate's laboratory has synthesized a MECA79
antibody-conjugated polymeric nanoparticle (MECA79-NP) that localizes specifically to the KLN during NTN.
The main objective of this proposal is to determine how the activation of FRCs promotes a pro-inflammatory
milieu in the KLN during CGN in order to identify new targets for a novel therapeutic strategy to combat CGN.
The aims of this proposal are to (1) explore the mechanism governing the adoption of a pro-inflammatory
phenotype by FRCs in the KLN during CGN, (2) investigate the role of FRCs in the expansion of the lymphatic
vasculature within the KLN during CGN, and (3) develop a first-in-class nanotherapeutic agent that delivers
ISAs to the KLN to suppress CGN effectively. The results from these studies...

## Key facts

- **NIH application ID:** 10145000
- **Project number:** 5K08DK124685-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Vivek Kasinath
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $168,489
- **Award type:** 5
- **Project period:** 2020-04-15 → 2025-04-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145000

## Citation

> US National Institutes of Health, RePORTER application 10145000, Role of Kidney-Draining Lymph Node in Crescentic Glomerulonephritis (5K08DK124685-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10145000. Licensed CC0.

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