# Mechanisms of immune dysregulation in human PI3Kgamma deficiency

> **NIH NIH R21** · YALE UNIVERSITY · 2020 · $251,251

## Abstract

Project Summary
 Many severe immune diseases in young patients with infection susceptibility and/or immune-mediated
tissue damage are caused by a single-gene defect resulting in an inborn error of immunity. We have a long-
standing interest in intensive investigation of severe immune diseases of childhood. Our approach is to pursue
rigorous genetic and immunologic studies that define the genes, cell types, and pathways underlying pathology
to glean clinically relevant insights into fundamental human biology directly from patients. Currently, the genetic,
molecular, and cellular drivers of susceptibility and pathogenesis in rare cases of severe SARS-CoV2-related
disease in young, otherwise healthy individuals are unknown. Defining these drivers will not only address the
urgent health needs of children and teenagers afflicted with the recently surging ‘multisystem inflammatory
syndrome in children’ (MIS-C) and severe respiratory manifestations associated with SARS-CoV2 infection but
will also provide fundamental knowledge about immunopathology mechanisms that are a general feature of
COVID-19 across the age spectrum. We have built an growing cohort of young COVID-19 patients and banked
DNA, cells, and serum from saliva and peripheral blood samples to enable us to tackle this urgent crisis. Our
preliminary data demonstrate feasibility to obtain suitable samples for multi-dimensional analysis of leukocytes
from these patients and also raise testable hypotheses about the initiating and triggering events in MIS-C. Using
primary human cells and cutting-edge technologies, two specific aims will be pursued. Aim 1) To define genetic
susceptibility to severe COVID-19 in young, otherwise healthy subjects. Aim 2) To elucidate immune
mechanisms mediating severe inflammatory responses in these children and teenagers. The results of these
investigations will provide significant insights into COVID-19 genetics and inflammation and will lay the
groundwork to help advance our understanding and treatment strategies for this world-wide pandemic.

## Key facts

- **NIH application ID:** 10178863
- **Project number:** 3R21AI144315-01A1S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Carrie L. Lucas
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $251,251
- **Award type:** 3
- **Project period:** 2020-08-14 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178863

## Citation

> US National Institutes of Health, RePORTER application 10178863, Mechanisms of immune dysregulation in human PI3Kgamma deficiency (3R21AI144315-01A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10178863. Licensed CC0.

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