Laboratory of Larisa Poluektova, MD, PhD
Research Goals
Together with Santhi Gorantla, we would like to provide biomedical community with environmentally, genetically, and xenotransplantation-modified mice for the study of human immunity, viral infections/co-infections and related comorbidities, drug interactions, and vaccines.
HIV-1 pathogenesis, therapeutics and vaccines, humanized mice for translational research, stem cell transplantation. The long range goals are to development small animal models to study the pathogenesis of human-specific viral co-infection - HIV-1 and HCV/HBV.
Techniques used in laboratory
- Hematopoietic stem cells and liver stem cells isolation and transplantation
- Creation of chimeric mice carrying human blood and liver
- FACS
- RT-PCR
- Immunohistochemistry
- Western blot
- Studies of adaptive immunity on humanized mice
Collaborators
Margaret R. Larson Professor of Internal Medicine and Infectious Diseases
Chair, Department of Pharmacology and Experimental Neuroscience
Professor and Chair, Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University
Chairperson, Department of Microbial Pathogens and Immunity, Rush University
General Manager, Central Institute for Experimental Animals, Japan
Chief Investigator, Central Institute for Experimental Animals, Japan
Funding
PI: L. Poluektova/S. Gorantla/C. Gurumurthy
Source: NIH/OD R21034048
We will create a new genetic background of immune deficient mice to improve their ability to support the development of human lymphoid organs and adaptive immunity to human-specific and emerging infections. New models will reflect the human immunity associated with multiorgan pathology and provide the biomedical community with tools for drug and vaccines discoveries, among other translational research.
PI: L. Poluektova/Edagwa/Osna
Source: NIH/NIAID 5R01AI163042
We will convert oral daily HBV treatment regimen (tenofovir and entecavir) and an immunomodulatory agent (tizoxanide) into medicines that can be administered once every two months. Lipophilic nanocrystals will be made from modified parent drugs then evaluated using in vitro and in vivo models to identify a safe and more effective two drug regimen to facilitate a functional cure strategy for HBV infection.
PI: L. Poluektova
Source: NIH/OD 5R24OD018546
Center will generate new strains of mice for humanization of blood and liver, and distribute among academic collaborators for acceleration of vaccine and drug development research.
PI: L. Poluektova
Source: NIH/NIDA 5R21DA041018
Proposes to adapt a humanized mouse model to validate the role of astrocytes and microglia as HIV reservoir s in the brain. Use of the human IL-34-expressing mouse as a driver for enhanced development and engraftment of human neural progenitor cells into glial and innate human immune cells provides the potential for development of a functional model with which to study HIV reservoirs in the brain and the effect of drugs of abuse.
PI: L. Poluektova
Source: NIAAA R01AA027189
Liver injury, which is characteristic of HIV-infection, is the second-leading cause of mortality in HIV-infected patients. The rapid progression of liver fibrosis is frequently associated with hepatitis B and C co-infections, but the mechanisms are not clear yet. Here, we examine how hepatitis C co-infection with HIV stress hepatocytes to secrete extracellular vesicles, which in turn initiate the cross-talk between liver parenchymal and nonparenchymal cells, thereby promoting inflammation and fibrosis development.
Multiple PI: L. Poluektova and H. Gendelman
Source NIH/NIA R01 AG043540
This proposal seeks to generate a solid understanding of the abilities to sustain long-acting nanoformulated antiretroviral therapies during aging. The work rests in the idea that these therapies that are given systemically and every week or month will not only be tolerated better for improving patient compliance but lead to reduced systemic toxicities and viral resistance patterns. The work entails an aggressive evaluation of dosing, immune senesence, tolerance and systemic effects of the nanoformulations. The work will be done in tandem with Dr. Larisa Poluektova and her laboratory in evaluation of specific CNS patterns for viral restriction and potential eradication employing current humanized mouse models and newer ones that are being developed where human glial cells are transplanted to a mouse brain.
PI: H. Gendelman; Core Leader: L. Poluektova
Source: NIH/NINDS P01DA028555
This is an integrative cross approach translational and multi-investigator program grant seeking to develop nanoformulated antiretroviral drug therapy from the bench to the patient.
PI: S. Maggirwa (U. Rochester); Co-I: L. Poluektova
Source: NIH/NINDS R01NS066801
To test whether activation of peripheral platelets by HIV-1 elicits abnormal effects on brain microvascular endothelial cells, thereby altering blood-brain barrier integrity and exacerbating inflammation in the CNS.
PI: H.E. Gendelman
Source: NIH/NIMH R01MH115860
Co-PI: L. Poluektova and C. Gurumurthy
Source: NIH/NIAID R01 AI147725-01
The application proposes to develop a novel mouse model dually transplanted with human hepatocytes and human immune cells that can be used to study Hepatitis B virus (HBV) and HIV co-infection