# Molecular Phenotyping of Autoimmunity in Tribal Members: Aiding Precision Medicine and Tribal Student Training

> **NIH NIH S06** · CHEROKEE NATION · 2021 · $373,899

## Abstract

Project Summary: 
 American Indians (AIs) have some of the shortest life-expectancies with geographic inequalities even more 
pronounced in rural counties like those in the Cherokee Nation catchment area. The causes for these findings 
are multi-factorial and are impacted by poorer outcomes in many chronic health conditions, such as the 
rheumatic diseases. Unfortunately, US tribal members have some of the highest rates of rheumatic disease in 
the nation, including diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and 
systemic sclerosis. To help address these health inequalities, this project seeks to understand the molecular 
immunologic phenotypes and potential mechanisms of accelerated aging in Oklahoma tribal patients to better 
inform diagnosis and treatments. Together, OMRF, OUHSC and the Cherokee Nation have assembled 
rheumatic disease research and infrastructure which are critical for the success of this proposed project, such 
as collections of samples and associated clinical data from 454 AI SLE patients, 190 AI RA patients and 300 AI 
controls, as well as thousands of additional patients and controls of other racial/ethnic backgrounds. Tribal 
NARCH rheumatology clinics have enrolled 273 additional tribal rheumatic disease patients. Joint findings to 
date include: it is common for tribal populations to have overlapping features of rheumatic disease (without 
meeting standard classification criteria), disease-specific autoantibody markers are not present in American 
Indian patients, and up to 41% of AI SLE patients have high concentrations of previously unidentified 
autoantibodies. Some unknown SLE specificities are directed against mitochondrial or myositis-specific 
antigens. Based upon these results, this application brings together three cutting-edge scientific approaches, 
precision medicine/deep molecular phenotyping, big data analytics/visualization and molecular mechanisms of 
accelerated aging, to identify dysregulated pathways in AI rheumatic disease patients. 
 We will address the associated hypotheses through the following aims: (1) Perform a comprehensive 
molecular phenotypic evaluation of serologic, gene expression and cellular evidence of autoimmune disease- 
associated changes in American Indian patients with SLE or RA compared to matched controls to identify 
unique and important disease pathways which are enriched in AI autoimmunity. (2) Evaluate American Indian 
rheumatic autoimmune disease patients for molecular evidence of accelerated aging. Our key personnel have 
mentored over 20 American Indian students to advanced degrees and academic, medical and tribal service 
careers as physicians, physician assistants, and scientists. This project provides additional training to tribal 
students, with the initial three already identified. Training in clinical research, data management, data analytics, 
clinical immunology and precision medicine will be provided to the tribal students and...

## Key facts

- **NIH application ID:** 10246869
- **Project number:** 5S06GM127983-04
- **Recipient organization:** CHEROKEE NATION
- **Principal Investigator:** JUDITH A JAMES
- **Activity code:** S06 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $373,899
- **Award type:** 5
- **Project period:** 2018-09-12 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246869

## Citation

> US National Institutes of Health, RePORTER application 10246869, Molecular Phenotyping of Autoimmunity in Tribal Members: Aiding Precision Medicine and Tribal Student Training (5S06GM127983-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246869. Licensed CC0.

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