# HPMI: Host Pathogen Mapping Initiative

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $2,489,172

## Abstract

THE HOST PATHOGEN MAP INITIATIVE 2.0
OVERALL SUMMARY
The Host-Pathogen Map Initiative (HPMI) 2.0 is an interdisciplinary program that aims to improve our
understanding of the interactions between host cellular systems and respiratory pathogens and builds upon the
success of its previous iteration. The ultimate goals are identifying therapeutic targets, treatment modalities, and
predicting disease severity. HPMI 2.0 will focus its efforts on the bacterial pathogen Mycobacterium tuberculosis
(Mtb) and viral respiratory pathogens such as SARS-CoV-2 and variants of concern, e.g. omicron and delta, as
well as influenza, parainfluenza virus, and respiratory syncytial virus, among other RNA viruses. We will use
proteomics, genetics and structural biology approaches to study the host factors relevant to these infectious
diseases in disease-relevant cell models and patient samples, and combine our data with existing -omic
datasets. Network and structure modeling approaches will be used to integrate these datasets to make testable
predictions about proteins, complexes and pathways in the host regulating infection as well as disease prognosis.
Our proposal will be centered on the profiling of human samples to decipher networks underlying infectious
respiratory diseases. To generate clinically relevant datasets on viral respiratory disease, we will use human
lung primary cells and three-dimensional human airway organoids (HAO) for systems biology analyses,
determine the global proteome of plasma samples from SARS-CoV-2-infected patients, and integrate our data
with clinical datasets. To uncover the determinants of the heterogeneity of susceptibility to TB, we will utilize
genome-wide association studies (GWAS) for TB susceptibility genes combined with whole genome sequences
of the infecting Mtb strain in a cohort of TB patients in Vietnam at the Oxford University Clinical Research Unit
(OUCRU). We will further profile alveolar macrophages and peripheral blood derived macrophages from healthy
donors to understand mechanisms of innate immune responses to Mtb infection and cell-type specific features.
We hypothesize that different TB clinical outcomes are regulated by specific molecular networks in infected
macrophages. Our models for the identification of combinatorial biomarkers to predict disease outcomes will be
assessed on the Mtb-infected cohort in Vietnam and COVID-19 patients at UCSF. Lastly, we will explore potential
commonalities between Mtb and SARS-CoV-2, as severe forms of TB and COVID-19 are accompanied by
exacerbated inflammatory responses and “cytokine storms”.
A better molecular understanding of the functions and mechanisms of host-pathogen complexes may reveal new
therapeutic strategies for intervention, including strategies of host-directed therapies that circumvent the
limitations of current drug regimens using antibiotics or antivirals where mutations in the pathogen proteins can
diminish drug efficacy. Our host-pathogen cell maps will help...

## Key facts

- **NIH application ID:** 10549996
- **Project number:** 2U19AI135990-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nevan J Krogan
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,489,172
- **Award type:** 2
- **Project period:** 2018-08-17 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10549996

## Citation

> US National Institutes of Health, RePORTER application 10549996, HPMI: Host Pathogen Mapping Initiative (2U19AI135990-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10549996. Licensed CC0.

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