# The Role of the Adaptor Protein SH2B3 in Type 1 Diabetes

> **NIH NIH K08** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $162,000

## Abstract

PROJECT SUMMARY/ABSTRACT:
This project is a NIH Mentored Clinical Scientist Research Career Development Award (K08) application for Dr.
Eric Allenspach, an Acting Assistant Professor in the Department of Pediatrics at the University of
Washington (UW). Dr. Allenspach has completed his clinical training in Pediatric Rheumatology and
Immunology and has both a clinical and research interest in the treatment of pediatric autoimmune conditions.
Dr. Allenspach's specific research interest is understanding the role of genetic risk factors in regulating the
myeloid lineage and the interaction between the innate and adaptive immune responses. His long-term career
goal is to establish himself as an independently-funded principle investigator studying these mechanisms in
both animal models and directly in primary human cells using basic science and translational approaches.
In order to achieve this goal, Dr. Allenspach is requesting the NIH K08 support for additional training and
mentorship in the following specific areas: (1) assessment of murine myelopoiesis and technical skills in ex
vivo manipulating human myeloid cells; (2) training in laboratory techniques related to gene knockdown and
gene editing; (3) additional training in proteomic approaches and big data analysis; (4) NOD murine modeling
of spontaneous diabetes. (5) presenting at scientific conferences, career development seminars, and additional
classroom-based training relevant to this project; and (6) grantsmanship and laboratory management with a
focus on developing an independent research focus with a goal of transitioning to scientific independence.
In the present application, Dr. Allenspach proposes studying the biologic role of an identified autoimmune risk
variant in the adaptor protein SH2B3 on the development of type 1 diabetes (T1D) and in regulating
myelopoiesis. A strong association has been found between a genetic allele (rs3184504) in the SH2B3 gene
and T1D. In this proposal, we utilize murine modeling to understand how reduced SH2B3 function affects
APCs during T1D development and under environmental stress. The overall goal of the project is to test
whether the SH2B3 risk variant alters T1D pathogenesis. These studies will focus on the following areas: In
Aim 1, we test does the SH2B3 T1D risk allele alter the inherent function of the myeloid APCs. As monocytes
are the precursors to several myeloid effector cells, we test in Aim 2 whether having more precursor
monocytes during inflammation lead to increased numbers of progeny including monocyte-derived DCs. In
Aim 3, we ask directly whether the rs3184504*T allele modeled in mice contributes to T1D by introducing the
genetic change on the NOD mouse background. In this proposal, we will directly assess the functional role for
this common risk variant in T1D, and, in parallel, gain new knowledge about monocyte biology relevant to T1D
pathogenesis. It is anticipated these studies would provide the publications and preliminary data n...

## Key facts

- **NIH application ID:** 9995488
- **Project number:** 5K08DK114568-03
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Eric J Allenspach
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $162,000
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995488

## Citation

> US National Institutes of Health, RePORTER application 9995488, The Role of the Adaptor Protein SH2B3 in Type 1 Diabetes (5K08DK114568-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9995488. Licensed CC0.

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