- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Adenosine and Purinergic Signaling
- CRISPR and Genetic Engineering
- HIV Research and Treatment
- Computational Drug Discovery Methods
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Nanowire Synthesis and Applications
- Autoimmune Bullous Skin Diseases
- Alzheimer's disease research and treatments
- Glycosylation and Glycoproteins Research
- Animal health and immunology
- Mosquito-borne diseases and control
- T-cell and B-cell Immunology
- Eosinophilic Disorders and Syndromes
- Drug-Induced Adverse Reactions
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Cholinesterase and Neurodegenerative Diseases
- Malaria Research and Control
- Immune Cell Function and Interaction
- Viral gastroenteritis research and epidemiology
- Advancements in Semiconductor Devices and Circuit Design
Stanford University
2022-2024
University of California, Merced
2013
The University of Western Australia
1999
Cleveland Clinic
1997
Regulatable CAR platforms could circumvent toxicities associated with CAR-T therapy, but existing systems have shortcomings including leakiness and attenuated activity. Here, we present SNIP CARs, a protease-based platform for regulating activity using an FDA-approved small molecule. Design iterations yielded cells that manifest full functional capacity drug no leaky in the absence of drug. In numerous models, were more potent than constitutive showed diminished T cell exhaustion greater...
Adenosine (Ado) mediates immune suppression in the tumor microenvironment and exhausted CD8+ CAR-T cells express CD39 CD73, which mediate proximal steps Ado generation. Here, we sought to enhance cell potency by knocking out CD39, or adenosine receptor 2a (A2aR) but observed only modest effects. In contrast, overexpression of deaminase (ADA-OE), metabolizes inosine (INO), induced stemness enhanced functionality. Similarly, exposure INO augmented function features stemness. profound metabolic...
Abstract The intensive nutrient requirements needed to sustain T cell activation and proliferation, combined with competition for nutrients within the tumor microenvironment, raise prospect that glucose availability may limit CAR-T function. Here, we seek test hypothesis stable overexpression (OE) of transporter GLUT1 in primary human cells would improve their function antitumor potency. We observe GLUT1OE increases consumption, glycolysis, glycolytic reserve, oxidative phosphorylation,...
Abstract Background Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma malignancies could disrupt the therapeutic landscape solid tumors. However, access to CAR-T is not adequate meet clinical needs, in part due high cost long lead times manufacturing grade virus. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 double-stranded DNA (dsDNA) or single-stranded (ssDNA) via homology-directed repair (HDR),...
The COVID-19 pandemic caused by SARS-CoV-2 exposed a global problem, as highly effective vaccines are challenging to produce and distribute, particularly in regions with limited resources funding. As an alternative, immunoglobulins produced eggs of immunized hens (IgY) can be simple inexpensive source for topical temporary prophylaxis. Here, we developed method extract purify IgY antibodies from egg yolks against viral pathogen-derived proteins using low-cost, readily available materials,...
Adenosine (Ado) mediates immune suppression in the tumor microenvironment and exhausted CD8
Abstract Chimeric antigen receptors (CARs) are synthetic that link an extracellular tumor specific domain to intracellular signaling domains. Despite of remarkable results against refractory B cell malignancies, intense effort is underway augment the potency CAR T cells in order overcome suppressive microenvironment, which associated with exhaustion. Adenosine a major mediator immune suppression. Ectoenzyme CD39 plays central role generation adenosine by catalyzing metabolism ATP into...
<h3>Background</h3> CAR T cells have been highly effective against refractory B cell malignancies but not demonstrated sustained antitumor effects solid tumors. Intense effort is underway to augment the potency of in order overcome suppressive tumor microenvironment, which associated with exhaustion. Adenosine a major mediator immune suppression. CD39 (ecto-ATP diphosphohydrolase-1) plays central role generation adenosine by catalyzing metabolism ATP into ADP/AMP. CD73 (59-ectonucleotidase)...