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HPMI: Host Pathogen Mapping Initiative

Award Number: U19AI135990
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/17/2018
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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HPMI: Host Pathogen Mapping Initiative - 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 build interpretable deep learning systems using state-of-the-art modeling approaches for prediction of infectious disease risk, disease severity and combinatorial risk factors for M. tuberculosis and SARS-CoV-2 infection in clinical settings.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $2,452,655 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	8	4/28/2026	NON-COMPETING CONTINUATION	$2,452,655
														Subtotal = $2,452,655

Issue Date FY: 2025 ( Subtotal = $2,546,034 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	003	7	8/8/2025	NON-COMPETING CONTINUATION	$2,464,183
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	004	7	8/26/2025	SUPPLEMENT FOR EXPANSION	$81,851
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	6	7/30/2025	NON-COMPETING CONTINUATION	$0
2025	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	4	11/25/2024	SUPPLEMENT FOR EXPANSION	$0
2025	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	4	11/25/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,546,034

Issue Date FY: 2024 ( Subtotal = $2,475,950 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	6	5/13/2024	NON-COMPETING CONTINUATION	$2,475,950
														Subtotal = $2,475,950

Issue Date FY: 2023 ( Subtotal = $2,489,172 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	5	8/2/2023	COMPETING CONTINUATION	$2,165,126
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	5	9/21/2023	COMPETING CONTINUATION	$324,046
														Subtotal = $2,489,172

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	4	2/25/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $3,000,000 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	4	8/4/2021	NON-COMPETING CONTINUATION	$2,000,000
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	4	8/10/2021	SUPPLEMENT FOR EXPANSION	$1,000,000
2021	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	3	7/12/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,000,000

Issue Date FY: 2020 ( Subtotal = $2,000,000 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	3	7/27/2020	NON-COMPETING CONTINUATION	$2,000,000
2020	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	2	5/12/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,000,000

Issue Date FY: 2019 ( Subtotal = $2,000,000 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	2	7/26/2019	NON-COMPETING CONTINUATION	$2,000,000
														Subtotal = $2,000,000

Issue Date FY: 2018 ( Subtotal = $2,000,000 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	1	8/15/2018	NEW	$2,000,000
														Subtotal = $2,000,000

Grand Total All Awards = $18,963,811

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HPMI: Host Pathogen Mapping Initiative

Award Number: U19AI135990

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/17/2018

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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