# Mechanisms of AIRE SAND-Domain Variants in Autoimmunity

> **NIH NIH K08** · UNIVERSITY OF COLORADO DENVER · 2020 · $184,788

## Abstract

Project Summary/Abstract
 This proposal for a five-year mentored research career development project focuses on the study of
AIRE protein function in the context of disease-causing mutations. The focused research aim of the proposal is
to understand the mechanism by which a novel mutation within the SAND domain of AIRE impairs the protein’s
function. The developmental aim of the proposal is further develop the applicant’s capability to understand the
functional impact of genetic variation on protein function, ultimately providing the groundwork for research that
directly ties genetic variation to clinical disease outcomes. The experiments outlined in the proposal include
genetic manipulations of expression vectors, expression of proteins in cell lines, various modes of protein
isolation, and immunologic characterization of mutant carrying mice. These experiments will be carried out
under the mentorship of Pippa Marrack, M.D., John Kappler, Ph.D., and Mark Anderson, M.D., Ph.D., leaders
in the fields of immunology and biochemistry.
 The candidate is currently an Assistant Professor of Pediatrics at National Jewish Health in the Division
of Allergy and Immunology. His primary interest is in monogenetic immune disease. His past work has involved
the characterization of novel forms of genetic primary immunodeficiency, and he has collaborated with multiple
prominent researchers to characterize novel genetic immune disorders identified in his patients. The outlined
proposal builds on the candidate’s previous research and clinical experience in the genetic cause of immune
deficiency, dysregulation, and dysfunction by attempting to understand the precise molecular mechanism by
which human-based mutations affect the AIRE protein. The development plan dramatically expands the
candidate’s capability to understand the relevance of genetic variants to protein structure and function. More
specifically, the proposed experiments and didactic work provide the opportunity to understand the function of
the AIRE protein, a protein that is essential for normal immune tolerance, and in which he previously identified
a novel functional mutation. More generally, the project will position the candidate with a unique set of cross
disciplinary skills that will enable him to transition to independence as a highly productive physician scientist in
the field of clinical immunology with particular insight into mechanisms of immune tolerance.

## Key facts

- **NIH application ID:** 10191520
- **Project number:** 7K08AI141734-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Jordan Abbott
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,788
- **Award type:** 7
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10191520

## Citation

> US National Institutes of Health, RePORTER application 10191520, Mechanisms of AIRE SAND-Domain Variants in Autoimmunity (7K08AI141734-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10191520. Licensed CC0.

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