# Disease Models and Mechanisms Core

> **NIH NIH P30** · YALE UNIVERSITY · 2020 · $273,662

## Abstract

Core B Project Summary/Abstract The past decade has seen quantum advances in the applications of 
technology to biomedical sciences. Among the more remarkable achievements has been the advent of whole 
genome sequencing allowing complete knowledge of the genomic DNA structure of innumerable organisms, 
CRISPR/Cas9 genome editing allowing ready manipulation of these genomes, and the advent of technological 
advances supporting proteomic analyses of complex biological systems, most notably humans. In order for 
researchers to achieve major advances in the study of human kidney diseases, it is imperative that we now 
apply these advances to in vivo mammalian models, in vitro cell systems and directed molecular assessments 
of human samples. The overarching objective of the Disease Models and Mechanisms Core is to facilitate 
application of these approaches to benefit and support human kidney disease-based mechanistic studies. In 
order to achieve this, the Core has developed research expertise in areas specifically targeted to reduce the 
barriers that hinder users pursuing bedside to bench research (Aims 1, 2 and 3) as well as those who seek to 
validate bench findings at the bedside (Aims 4 and 5). 
To support users who are pursuing mechanistic understanding of the recent wealth of human genome 
sequence information, the first 2 aims provide complementary expertise in manipulating the mouse genome in 
order to develop orthologous animal models and cell lines that faithfully replicate human disease pathogenesis. 
The first aim of the Core provides support for using bacterial artificial chromosomes as a means to perform 
complex modifications of specific genes including insertion of multiple epitope tags, fluorescent tags, point 
mutations, and deletions, followed by expression in mouse strains. The second aim provides a complimentary 
approach to genome editing using CRISPR/Cas9 for introducing genetic variants into cell lines and mouse 
models. The third component of the Core serves to distribute mouse strains and cell lines, for which distribution 
permission is granted, to users at a minimal cost-recovery price. This includes distribution of the Rosa-DTRfl 
“Terminator” mouse for isolation of large quantities of highly purified, non-immortalized renal cell types. The 
last two components of the Core have been developed to support users who wish to translate bench findings to 
better understand human kidney disease. In the fourth Aim, users are provided with resources and expertise in 
performing targeted proteomics of human urine to quantitatively assess >250 urinary proteins. In the final aim, 
the Core has developed a multiplexed approach to simultaneously analyze the amount and location of up to 42 
proteins in human kidney biopsy specimens using Imaging Mass Cytometry. These combined services 
advance the fields of renal research, enhance the mission of NIDDK and are of value to the broader renal 
research community.

## Key facts

- **NIH application ID:** 9987625
- **Project number:** 5P30DK079310-13
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** STEFAN SOMLO
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $273,662
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987625

## Citation

> US National Institutes of Health, RePORTER application 9987625, Disease Models and Mechanisms Core (5P30DK079310-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987625. Licensed CC0.

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