# Project 1 - BIDMC

> **NIH NIH P01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $917,554

## Abstract

A quarter to more than one half of the ~ one million people with systemic lupus erythematosus (SLE) in North
America will either present with lupus nephritis (LN) or will develop LN at some point in the course of their
disease. The available treatment tools include immunosuppressive drugs and the recently added Benlysta and
the calcineurin inhibitor, voclosporin. They are not specific drugs with the first three causing major side effects,
whereas, the last two have a small, albeit desirable, clinical benefit. Better understanding of the pathogenesis
of LN will advance our progress towards the development of reliable biomarkers and approaches to treat
patients in a precise manner. Early studies have indicated that kidney resident cells (podocytes, mesangial
and tubular epithelial cells) when exposed to the autoinflammatory environment that is prevalent in patients
with LN, they upregulate immunomodulatory molecules including a serine/threonine kinase IV (CaMK4) and
interleukin 23 receptor (IL-23R) which enable kidney inflammation and damage. When kidney resident cells
lack any of these molecules, inflammation is averted. Importantly, urine podocytes and tubular epithelial cells
present molecular abnormalities which reflect those in the kidney tissue. In this project, the hypothesis will be
tested that in response to peripheral autoimmune elements, kidney resident cells undergo molecular changes
which are requisite for the development of kidney inflammation and injury. The hypothesis will be tested in
three sets of experiments. In the first it will be demonstrated that CaMK4 and IL-23R in podocytes are
requisite for the development off LN; in the second it will be demonstrated that upregulation of CaMK4 and IL-
23R in tumular epithelial cells alters their metabolic profile and enables them to produce chemokines that
attract inflammatory cells leading to LN; in the third a pilot clinical study will be performed to first demonstrate
that upregulation of CaMK4 and IL-23R in urine cells reflects kidney tissue pathology, and second, that the
recording of these molecules in the urine can predict the development of LN in patients with SLE. The project
will use a number of novel tools availed in the laboratory and by the cores (single cell and spatial
transcriptomics and nanoparticle delivery of medicine to kidney resident cells) of this project program grant
along with conditionally knock out mice and a well-established lupus cohort. The project addresses directly
three unmet needs in LN: understanding of pathogenesis, development of precision treatment approaches and
high-fidelity biomarkers.

## Key facts

- **NIH application ID:** 10763720
- **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:** $917,554
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763720

## Citation

> US National Institutes of Health, RePORTER application 10763720, Project 1 - BIDMC (1P01AI179405-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10763720. Licensed CC0.

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