# Investigation of non-HIV Collapsing Glomerulopathy

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2020 · $533,433

## Abstract

Abstract
Collapsing glomerulopathy is a severe form of human glomerular disease that frequently results
in rapid progression towards end stage kidney failure. Whereas this disease can be caused by
HIV infection and other causes, this proposal will focus on a specific form of this disease caused
by circulating proteins (hereon referred to as CG). Although currently classified as a form of
focal and segmental glomerulosclerosis(FSGS), there are several molecular and morphological
differences that set CG apart from other forms of FSGS. The applicants developed the first ever
animal model of CG by injecting plasma from CG patients into a specific stain of inbred Sprague
Dawley rats (IMC rats) over a decade ago. Further exploration of this model, and correlation of
its molecular changes with human kidney biopsies resulted in the development of new
mechanism based models that will be utilized in this proposal.
The proposal is structured to explore two distinct morphological aspects of CG, epithelial cell
proliferation and glomerular capillary loop collapse, at a molecular level and also explore cross
talk between these two components of CG. Finally, a proteomic approach will be used to identify
and create a short list of circulating proteins that cause this disease. De-identified human
plasma and controls, and plasmapheresis samples from patients with recurrent CG after
transplantation (referred to as CG plasma) will be used for these studies.
The overall goal of the proposed studies is to develop new insight into the molecular
pathogenesis of CG so as to be able to develop new therapies for this disease.
In Specific Aim 1, molecular mechanisms of podocyte proliferation induced by ZHX2 and TERT
will be explored using podocyte specific ZHX2 transgenic rats and TERT knockout rats in the
IMC background injected with CG plasma.
In Specific Aim 2, a new model of CG developed in β5 integrin knockout mice will be used to
study the role of β3 integrin in the development of glomerular capillary loop collapse. Mice
deficient in β3 integrin and podocyte specific β3 integrin knockout mice will be used to study the
role of β5 integrin in CG. Rrm2b and β5 integrin knockout mice will be interbred to study
pathway synergies. Finally, crosstalk studies between the podocyte and the endothelium during
the pathogenesis of CG will be explored.
In Specific Aim 3, CG and control plasma will be depleted of 14 common plasma proteins, their
ability to induce CG changes confirmed, and the putative circulating proteins identified using a
proteomics approach comprising of DIGE and nano-LC MS/MS. A short list of proteins will be
tested in vitro and in vivo using the above animal models for their ability to induce CG.

## Key facts

- **NIH application ID:** 9985609
- **Project number:** 5R01DK111102-05
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Sumant Singh Chugh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $533,433
- **Award type:** 5
- **Project period:** 2016-09-05 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985609

## Citation

> US National Institutes of Health, RePORTER application 9985609, Investigation of non-HIV Collapsing Glomerulopathy (5R01DK111102-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9985609. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*