A5042350728- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Cancer, Stress, Anesthesia, and Immune Response
- SARS-CoV-2 and COVID-19 Research
- Phagocytosis and Immune Regulation
- Hippo pathway signaling and YAP/TAZ
- HIV Research and Treatment
- Pediatric Pain Management Techniques
- Virology and Viral Diseases
- Cytomegalovirus and herpesvirus research
- Mosquito-borne diseases and control
- Viral Infectious Diseases and Gene Expression in Insects
- interferon and immune responses
- Engine and Fuel Emissions
- Herpesvirus Infections and Treatments
- Advanced Combustion Engine Technologies
- Immune cells in cancer
- Neuroendocrine regulation and behavior
- Cell death mechanisms and regulation
- Mesenchymal stem cell research
- Monoclonal and Polyclonal Antibodies Research
- Embedded Systems and FPGA Design
- T-cell and Retrovirus Studies
University of California, Los Angeles
2011-2024
Black AIDS Institute
2011-2024
Broad Center
2013
UCLA Health
2007-2013
UCLA Jonsson Comprehensive Cancer Center
2010
Oita University
2002
Kumamoto University
1995-1998
Mansoura University
1995
Our laboratory has recently characterized a population of cells from adipose tissue, termed processed lipoaspirate (PLA) cells, which have multi-lineage potential similar to bone-marrow-derived mesenchymal stem (MSCs). This study is the first comparison PLA and MSCs isolated same patient. No significant differences were observed for yield adherent stromal growth kinetics, cell senescence, differentiation capacity, gene transduction efficiency. Adipose tissue an abundant easily procured...
Metastasis to distant tissues is the chief driver of breast cancer-related mortality, but little known about systemic physiologic dynamics that regulate this process. To investigate role neuroendocrine activation in cancer progression, we used vivo bioluminescence imaging track development metastasis an orthotopic mouse model cancer. Stress-induced had a negligible effect on growth primary tumor induced 30-fold increase including lymph nodes and lung. These effects were mediated by...
Coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 defined symptoms, but cardiac complications including viral myocarditis are also prevalent. Although ischemic and inflammatory responses can detrimentally affect function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes not well understood. Here, we utilize induced pluripotent stem cell-derived (hiPSC-CMs) as model to examine mechanisms...
ABSTRACT We recently demonstrated that a soluble protein, Gas6, can facilitate viral entry by bridging envelope phosphatidylserine to Axl, receptor tyrosine kinase expressed on target cells. The interaction between phosphatidylserine, and Axl was originally shown be molecular mechanism through which phagocytes recognize exposed dead Since our initial report, several groups have confirmed Axl/Gas6, as well other receptors, of dengue, West Nile, Ebola viruses. Virus binding is now generalized...
We have characterized a population of mesenchymal progenitor cells from adipose tissue, termed processed lipoaspirate (PLA) cells, which multilineage potential similar to bone marrow-derived stem and are also easily expanded in culture. The primary benefit using tissue as source is its relative abundance ease procurement. examined the infection PLA with adenoviral, oncoretroviral, lentiviral vectors. demonstrate that can be transduced vectors at high efficiency. maintain transgene expression...
ABSTRACT Targeted stable transduction of specific cells is a highly desirable goal for gene therapy applications. We report an efficient and broadly applicable approach targeting retroviral vectors to cells. find that the envelope alphavirus Sindbis virus can pseudotype human immunodeficiency type 1- murine leukemia virus-based vectors. When modified contain Fc-binding domain protein A, this gives significant enhancement in specificity combination with antibodies HLA CD4 relative without...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the Disease 2019 (COVID-19) pandemic, causes respiratory failure and damage to multiple organ systems. The emergence of viral variants poses a risk vaccine failures prolongation pandemic. However, our understanding molecular basis SARS-CoV-2 infection subsequent COVID-19 pathophysiology is limited. In this study, we have uncovered critical role evolutionarily conserved Hippo signaling pathway in pathogenesis. Given...
RNA interference is an evolutionarily conserved process of gene silencing that in plants serves as a natural defense mechanism against exogenous viral agents. becoming important tool for the study biological processes through reverse genetics and has potential therapeutic applications humans; however, effective delivery still major issue. Small interfering (siRNA) short hairpin (shRNA) have been introduced into cells by transfection chemically synthesized expression via plasmid cassettes...
ABSTRACT Redirecting the tropism of viral vectors enables specific transduction selected cells by direct administration vectors. We previously developed targeting lentiviral pseudotyping with modified Sindbis virus envelope proteins. These proteins have mutations in their original receptor-binding regions to eliminate natural tropisms, and they are conjugated proteins, including antibodies peptides, confer tropisms on target cells. investigated whether our interact DC-SIGN, which traps many...
ABSTRACT Recently, gene therapy vectors based upon the human immunodeficiency virus type 1 (HIV-1) genome have been developed. Here, we create an HIV-1 vector which is defective for all genes, but maintains cis -acting elements required efficient packaging, infection, and expression. In T cells transduced by this vector, expression low efficiently induced following infection. Remarkably, although does not contain specific anti-HIV-1 therapeutic presence of alone sufficient to inhibit spread...
Prostate cancer dissemination is difficult to detect in the clinic, and few treatment options exist for patients with advanced-stage disease. Our aim was investigate role of tumor lymphangiogenesis during metastasis. Further, we implemented a noninvasive molecular imaging technique facilitate assessment metastatic process. The potentials several human prostate xenograft models, LAPC-4, LAPC-9, PC3 CWR22Rv-1 were compared. cells labeled luciferase, bioluminescence reporter gene, enable...
Targeted gene transduction to organs and tissues of interest is the ultimate goal therapeutic delivery. Lentiviral vectors (LVs) are powerful tools for stable delivery but their integration into undesired cell types poses a serious safety concern use in clinic. Here we report development new dual-targeted LV that can preferentially home express prostate cancer bone metastases vivo after systemic Transductional targeting mediated by modified Sindbis virus envelope interacts with stem antigen...
Targeted gene transduction in vivo is the ultimate preferred method for delivery. We previously developed targeting lentiviral vectors that specifically recognize cell surface molecules with conjugated antibodies and mediate targeted both vitro vivo. Although effective some experimental settings, conjugation of virus mediated by interaction between protein A Fc region antibodies, which not as stable covalent conjugation. have now a more strategy utilizing avidin biotin.We inserted...
ABSTRACT Sophisticated retargeting systems for lentiviral vectors have been developed in recent years. Most seek to suppress the viral envelope's natural tropism while modifying receptor-binding domain such that its is determined by specificity of engineered ligand-binding motif. Here we took advantage Nipah virus (NiV), whose attachment envelope glycoprotein has picomolar affinity ephrinB2, a molecule proposed as molecular marker “stemness” (present on embryonic, hematopoietic, and neural...
Angiogenesis is a rate-limiting factor for numerous human diseases. Angiogenic vessels and also the endothelium of certain organs such as lung display molecular addresses that can be exploited selective delivery gene therapeutics. Lentiviral vectors (LVs) are powerful tools stable but their integration expression in undesired cell types poses serious safety concern. We have developed dual-targeted LV specifically target primary endothelial cells (ECs). Cell selectivity achieved during entry,...
Abstract Background Targeting gene therapy vectors that can home in on desired cell and tissue types vivo comprise the ultimate delivery system. We have previously developed targeting lentiviral by pseudotyping with modified Sindbis virus envelope proteins. The protein contains Fc‐binding region of A (ZZ domain), so be conjugated antibodies. antibody mediates specific transduction cells tissues expressing target antigens, both vitro . However, more stable conjugation molecules would optimal...
Zika virus (ZIKV) is a re-emerging flavivirus that has caused large-scale epidemics. Infection during pregnancy can lead to neurologic developmental abnormalities in children. There no approved vaccine or therapy for ZIKV. To uncover cellular pathways required ZIKV be therapeutically targeted, we transcriptionally upregulated all known human coding genes with an engineered CRISPR–Cas9 activation complex fibroblasts deficient interferon (IFN) signaling. We identified Ras homolog family member...
Specifically and effectively directing a therapeutic gene to its intended site of action is critical issue for translation basic genomics clinical therapy. Delivering therapy vectors specific cells or tissues through intravenous injection the most desirable method this purpose. In 2001, we reported successful targeted transduction in vitro utilizing both oncoretroviral lentiviral pseudotyped with chimeric Sindbis virus envelope (ZZ SINDBIS). However, these pseudotypes mediated nonspecific...