# Project 2

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $107,532

## Abstract

PROJECT ABSTRACT
The SARS coronavirus-2 (SARS-CoV-2) has rapidly emerged over the past four months leading to a critical
pandemic of coronavirus disease (COVID-19) with over 1.4M cases worldwide
(https://coronavirus.jhu.edu/map.html) and roughly 100,000 projected fatalities in the US alone by August
2020 (See https://covid19.healthdata.org/projections). SARS-CoV-2 causes a lethal ARDS. Despite our
improved mechanistic understanding of ARDS, intervention clinically is challenging. NOT-AI-20-31 indicated
several needs, such as development of reagents and assays for virus characterization, understand critical
aspects of viral infection, replication, pathogenesis, and transmission, identification and evaluation of the
cellular and humoral immune responses to SARS-CoV-2, which we address in this proposal.
 Indeed, there is an urgent need to understand the immunopathology of COVID-19 and study the
interactions of the lung epithelium and tissue, the immune system and the virus to understand the biology of
this multipartite interaction. We need to better understand the immunopathology of COVID-19 to explore
novel therapeutic approaches that have the potential to work in COVID-19 patients.
 Our proposal addresses this need from the perspective of the lung epithelium response to SARS-
CoV-2 infection and from a T cell perspective in COVID-19. Simultaneously, or efforts will also provide a
sharable research platform of lung airway organoids/SARS-CoV-2/immune cells that will expedite testing of
experimental therapeutics. Results from my supplement program will be shared with Drs. Gordon, Looney,
and Krummel in our ‘RapidPath’ program (see supporting letter) to promote rapid discovery and progress
and will be compared to insights from COVID-19 patient immune systems, being simultaneously profiled in
the UCSF IMPACC project. In this this Administrative Supplement we will capitalize on my lab’s established
expertise in T cell signaling, T cell activation, antigen recognition, inflammation, and autoimmune diseases.
Those are broad topics of the parent P01 (2P01AI091580, Weiss). Uniquely, we will combine our T cell
expertise with our expertise in the generation and studies of epithelial cell organoids. We already have an
“Airway Organoid Biobank” that we will expand as a resource for the community. We will characterize the
epithelial response to six different SARS-CoV-2 strains compared to H1N1pdm virus, using airway
organoid-, single cell RNAseq-, and CyTOF- technology (Aim 1). In order to better understand SARS-CoV-2
and adaptive immunity, we will obtain mechanistic insights into T cell activation and T cell signaling in the
context of SARS-CoV-2- and H1N1pdm- infection of seven, diverse Airway Organoids and two NSCLC
organoids (Aim 2). High-resolution imaging and CyTOF analysis of these “virus-T cell-organoids” will
provide much needed immunological insights into SARS-CoV-2 and its T cell biology as indicated in NOT-
AI-20-31 and will synergize with other proj...

## Key facts

- **NIH application ID:** 10159451
- **Project number:** 3P01AI091580-09S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** JEROEN ROOSE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $107,532
- **Award type:** 3
- **Project period:** 2020-05-18 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159451

## Citation

> US National Institutes of Health, RePORTER application 10159451, Project 2 (3P01AI091580-09S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10159451. Licensed CC0.

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