This proposal seeks funds to establish a Center for Humanized Mice Development. This new facility at the University of Nebraska Medical Center (UNMC) will offer environmentally, genetically, and xenotransplantation- engineered mouse models for translational studies and drug discovery, which are the mainstream at UNMC. It is well known that often clinical studies are successful in animal models but fail at the human level. Also the focused use of micro-animals, mice in particular, makes applicability to humans problematic. In turn, we are developing a resource that will generate improved animal models to study human immunity, human-specific infections, vaccines, and human-specific drug interactions. The resources are expected to be efficiently utilized for speeding the translation of new therapeutics to patients. Our goals to improve existing strains of mice are as follows: modify mouse backgrounds for the studies of human-like adaptive immune responses to broader range of pathogens and evaluation of vaccine candidates, create strains of mice that are compatible with the function of human immune system based on human-like glycosilation patterns, modify mouse backgrounds for studies of human-like drug metabolism and drug interaction, study HIV-1-related co-infections, such as hepatitis, tuberculosis, and malaria, and lastly examine HIV-1-associated comorbidities, including end-organ diseases like HIV-1-associated neurocognitive disorders (HAND).

Public Health Relevance

Nebraska Center for Humanized Mice Development will provide biomedical community with environmentally, genetically, and xenotransplantation-modified mice for the studies on human immunity, viral infections/co-infections and related comorbidities, drug interactions, and vaccines.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
5R24OD018546-02
Application #
8881366
Study Section
Special Emphasis Panel (ZRG1-BBBP-J (45))
Program Officer
Mirochnitchenko, Oleg
Project Start
2014-07-01
Project End
2018-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
2
Fiscal Year
2015
Total Cost
$692,358
Indirect Cost
$232,319
Name
University of Nebraska Medical Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Sillman, Brady; Bade, Aditya N; Dash, Prasanta K et al. (2018) Creation of a long-acting nanoformulated dolutegravir. Nat Commun 9:443
Dagur, Raghubendra Singh; Wang, Weimin; Cheng, Yan et al. (2018) Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice. Biol Open 7:
McMillan, JoEllyn M; Cobb, Denise A; Lin, Zhiyi et al. (2018) Antiretroviral Drug Metabolism in Humanized PXR-CAR-CYP3A-NOG Mice. J Pharmacol Exp Ther 365:272-280
Araínga, Mariluz; Edagwa, Benson; Mosley, R Lee et al. (2017) A mature macrophage is a principal HIV-1 cellular reservoir in humanized mice after treatment with long acting antiretroviral therapy. Retrovirology 14:17
Li, Weizhe; Gorantla, Santhi; Gendelman, Howard E et al. (2017) Systemic HIV-1 infection produces a unique glial footprint in humanized mouse brains. Dis Model Mech 10:1489-1502
Gnanadhas, Divya Prakash; Dash, Prasanta K; Sillman, Brady et al. (2017) Autophagy facilitates macrophage depots of sustained-release nanoformulated antiretroviral drugs. J Clin Invest 127:857-873
Araínga, Mariluz; Su, Hang; Poluektova, Larisa Y et al. (2016) HIV-1 cellular and tissue replication patterns in infected humanized mice. Sci Rep 6:23513
Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael et al. (2016) Metabolic drift in the aging brain. Aging (Albany NY) 8:1000-20
Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B et al. (2016) Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID ""Meet the Experts"" 2015 Workshop Summary. AIDS Res Hum Retroviruses 32:109-19
Quadros, Rolen M; Poluektova, Larisa Y; Gurumurthy, Channabasavaiah B (2016) Simple and reliable genotyping protocol for mouse Prkdc(SCID) mutation. J Immunol Methods 431:60-2

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