# Lupus nephritis: novel insights in the pathogenesis and treatment

> **NIH NIH P01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $2,265,718

## Abstract

Overall Abstract
Little is known about the pathogenesis of lupus nephritis (LN), particularly as it relates to the initiation and 
propagation of the inflammatory response which accounts for the development or end stage renal disease. LN 
may complicate up to two thirds of patients with systemic lupus erythematosus with higher rates commonly seen 
people of Black and Asian backgrounds. Besides the needle kidney biopsy, we lack tools that reflect tissue 
pathology with fidelity. Although two drugs have been recently approved to treat patients with LN, all treatment 
protocols involve systemic administration of drugs or biologics which are laden with side effects and limited 
clinical efficacy. Ample evidence has revealed that kidney resident cells and newly formed high endothelial 
venules in the presence of an autoinflammatory environment, upregulate molecules which account for the 
ensuing inflammation and cell damage, while in their absence, kidney damage is averted. These molecular 
changes can be recorded in parallel in podocytes and tubular epithelial cells in the urine. This proposal will test 
the hypothesis that interaction of constituents of the immune system with kidney resident cells and the ectopically 
formed high endothelial venules, determines the development of inflammation and injury in the setting of LN. 
Corollaries of this hypothesis are that kidney resident cells can serve as gateways for the administration of 
targeted therapeutics for the treatment of LN and that kidney tissue pathology can be recorded with high fidelity in 
the urine cells of patients with LN. There are 2 projects in this proposal: 1) Interplay between autoimmune 
effectors and kidney resident cells in lupus nephritis and 2) Newly formed high endothelial cells in the kidneypathogenesis and implications in lupus nephritis. The proposal will be supported by 3 cores: The Administrative 
Core will be responsible for regulatory compliance, budget management, scheduling meetings. The Nanoparticle 
Immune Delivery Core will be responsible for the construction of nanoparticles loaded with drugs and biologics 
and tagged with antibodies for cell-specific delivery. The Single Cell, Spatial Transcriptomics and Bioinformatics 
Core will perform single cell transcriptomics studies and will provide statistical and bioinformatics support. This 
proposal through extensive synergistic plans between the project leaders brings forward novel and significant 
elements in the study of the pathogenesis, treatment and biomarker development in patients with LN.

## Key facts

- **NIH application ID:** 10763716
- **Project number:** 1P01AI179405-01
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** George C Tsokos
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,265,718
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763716

## Citation

> US National Institutes of Health, RePORTER application 10763716, Lupus nephritis: novel insights in the pathogenesis and treatment (1P01AI179405-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10763716. Licensed CC0.

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