To develop novel gene therapy vectors for introducing novel genes that block HIV replication into HSCs; in vivo testing of genetically-modified HSCs; methods to mobilize HSCs from bone marrow

Utilize genetic modification of HSCs to develop cell-based therapies for treating AIDS; employ non-human primate models for studying vaccination strategies against SIV/HIV; develop new strategies for creating HIV-resistant stable T cell populations that can restore immune function in AIDS patients.

Employ non-human primate models for studying SIV and HIV infection; develop novel gene therapy-based methods for combating HIV infection, such as modifying HSCs to generate HIV resistance; explore the compromised surveillance mechanisms associated with T-cell pathophysiology resulting from SIV/HIV infection; investigate immune-mediated avenues for HIV vaccination; study novel cell culture methods to boost T-cell development from precursor hematopoietic stem cells.

• In vitro experiments with novel lentiviral transduction vectors for shuttling HIV inhibitory sequences into hematopoietic cells are yielding potential new approaches for blocking HIV replication as well as generating stable populations of HIV-resistant immune cells that can repopulate the immune system
   
• In vivo studies in non-human primates, one of the best animal models for exploring new therapies to combat AIDS, are uncovering important insights into immune responses to SIV/HIV infection, T and B lymphocyte surveillance and stability, and HIV vaccine development
   
• Design new chimeric lentiviral vectors that more authentically model HIV infection in non-human primates, as well as capitalize on new molecular findings to develop new non-human primate models that are more permissive for HIV infection
   
• Maximize in vitro T-cell production from hematopoietic precursor cells
   

Non-human primate models for SIV/HIV infection; Lentiviral-based gene therapy into HSCs; Multiparameter flow cytometry to monitor immune system reconstitution
 

Dr. Johnson has a longstanding interest in immune regulation, lymphocyte biology, and primates and humans infected with SIV and HIV, respectively, as a means for developing more effective and less toxic therapies for the treatment of AIDS. He has published important studies on the effects of SIV infection on T lymphocytes, in order to model HIV infection in humans. Dr. Johnson has characterized in detail features of protective T cell responses induced by live attenuated SIV vaccines. His recent investigations have delved into new primate models for studying SIV infections, chimeric SIV/HIV-1 viruses, and novel gene therapy approaches for blocking SIV/HIV replication.

Biological Mechanisms and Pathways

• Hematopoietic Stem Cell •
• HSC •
• HSC •
• Immunology •
• T lymphopoiesis •
• T-cell
•  

Disease Mechanisms

• AIDS •
• HIV •
• Lentivirus •
• SIV
•  

Immunology

• Immunology
•  

Infectious Disease

• HIV
•  

Research Tools and Instrumentation

• Gene knockdown •
• Immune reconstitution •
• Immunotherapy •
• Primate Model •
• Rhesus macaque •
• RNA inhibition •
• Stem cell gene therapy
•  

Therapeutics

• Immunotherapy •
• Stem cell gene therapy •
• Vaccine
•