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Characterization of a humanized mouse model to study HIV and ARV effects on bone

Award Number: R21AR079309
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary / Abstract The development of highly effective antiretroviral (ARV) therapies has significantly increased the lifespan of people living with HIV (PLWH). Yet as HIV has become a chronic disease, it is becoming increasingly clear that PLWH have an increased risk for and an earlier onset of a variety of comorbidities, including osteoporosis. Our long-term goal is to identify the mechanism(s) of HIV and ARV-mediated bone loss. While human studies are highly valuable in defining phenomena and associations, they are complicated by sample accessibility, numerous confounding variables, and limitations in assessing cause and effect. Small animal models can be of value to probe the mechanism(s) implicated in HIV/ARV-induced bone loss. However, a critical barrier in the field is the difficulty in modeling HIV infection and ARV treatment in small animal models. Although several rodent models have been used to study the effects of HIV on bone, each has its own unique limitations. Therefore, in the current proposal we aim to characterize the NSG-HuPBMC mouse model to study the effects of HIV infection and ARV treatment on bone. The model has several key advantages: (1) it is relatively cost effective and less complex than other models, (2) allows for reconstitution and infection of cells of interest, and (3) there is no irradiation or fetal tissue required. The proposal will test the hypothesis that both HIV infection and ARV treatment induce loss of bone mass and reduced bone quality and strength in NSG-HuPBMC mice via two separate but independent aims that will determine the effects of HIV infection (Aim 1) and ARV treatment alone and in combination with HIV infection (Aim 2) on bone. The research proposal is well suited as a high risk/ high reward R21 application because assessing bone loss in this model can potentially establish it as a suitable model for studying HIV skeletal co-morbidities and most importantly define mechanisms that may inform the human condition.


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: 2023 ( Subtotal = $0 )
2023	2021	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	8/23/2023	NEW	$0
2023	2021	RUSH UNIVERSITY MEDICAL CENTER	1620 W HARRISON ST	CHICAGO	IL	60612	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	12/7/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	10/11/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $404,063 )
2021	2021	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/25/2021	NEW	$404,063
														Subtotal = $404,063

Grand Total All Awards = $404,063

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Characterization of a humanized mouse model to study HIV and ARV effects on bone

Award Number: R21AR079309

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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