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Collaborative Integration of Hepatitis B Molecular Virology and Mathematical/Computational Modeling

Award Number: R01AI144112
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Despite an effective vaccine, hepatitis B virus (HBV) continues to impose an enormous global health burden. Over 260 million are HBV infected worldwide, causing chronic hepatitis and more than 400,000 death per year due to hepatocellular carcinoma. While currently available drugs can suppress HBV replication only a small subset of patients are cured. As such, a deeper understanding of HBV infection dynamics at the molecular level is needed to enable the development of more effective (i.e. curative) therapeutics. Fortunately, significant advances have been made recently with the establishment of chimeric mouse models with humanized livers that retain permissiveness to HBV infection and the identification of sodium taurocholate cotransporting polypeptide (NTCP) as the HBV entry receptor which when expressed exogenously renders hepatoma cell cultures permissive to HBV infection in vitro. Hence, for the first time, we can perform HBV infections in mice and cell culture to characterizing HBV lifecycle and treatment response. Towards this end, the objective of this cross disciplinary R01 is to increase our knowledge of HBV by formulating and testing mathematical/computational models of HBV infection. The premise is that a more quantitative understanding of HBV infection and treatment dynamics will help define rate limiting steps, identify more effective antiviral targets and predict mechanism of action (MOA) of current drugs and those under development thus facilitating the design of improved therapeutics. The uniquely close collaborative effort among experienced virologists and expert viral dynamic and computational scientists proposed is critical for facilitating the development and utilization of data-driven modeling concepts to elucidate the detailed molecular biological processes that regulate HBV. Specifically, we propose to (i) Quantify HBV infection kinetics in uPA-SCID chimeric mice with humanized livers and develop mathematical/computational models to elucidate the processes that regulate HBV dynamics, (ii) Refine our understanding of HBV infection at the molecular level by characterizing HBV infection kinetics in vitro and developing multi-compartmental mathematical/computational models to elucidate the processes that regulate HBV dynamics, (iii) Validate and refine our understanding of HBV infection by characterizing/ modeling HBV treatment response to antivirals of known mechanism of action, and (iv) Use HBV mathematical/computational models to predict the MOA by which clinically relevant drugs inhibit HBV and empirically test those hypotheses.


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: 2025 ( Subtotal = $0 )
2025	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	5	12/10/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $407,382 )
2023	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	5	12/6/2022	NON-COMPETING CONTINUATION	$407,382
														Subtotal = $407,382

Issue Date FY: 2022 ( Subtotal = $414,043 )
2022	2022	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	4	12/17/2021	NON-COMPETING CONTINUATION	$414,043
														Subtotal = $414,043

Issue Date FY: 2021 ( Subtotal = $420,892 )
2021	2021	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	3	12/29/2020	NON-COMPETING CONTINUATION	$420,892
														Subtotal = $420,892

Issue Date FY: 2020 ( Subtotal = $450,911 )
2020	2020	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	2	12/19/2019	NON-COMPETING CONTINUATION	$450,911
														Subtotal = $450,911

Issue Date FY: 2019 ( Subtotal = $471,058 )
2019	2019	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	1	1/15/2019	NEW	$471,058
														Subtotal = $471,058

Grand Total All Awards = $2,164,286

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Collaborative Integration of Hepatitis B Molecular Virology and Mathematical/Computational Modeling

Award Number: R01AI144112

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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