A5034967094- CAR-T cell therapy research
- Endoplasmic Reticulum Stress and Disease
- Genetics, Aging, and Longevity in Model Organisms
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Adipose Tissue and Metabolism
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Chemical Reactions and Isotopes
- Heat shock proteins research
- Genomics, phytochemicals, and oxidative stress
- Receptor Mechanisms and Signaling
- Autophagy in Disease and Therapy
- Metabolism and Genetic Disorders
- Garlic and Onion Studies
- Advancements in Semiconductor Devices and Circuit Design
- Nanowire Synthesis and Applications
- Neuropeptides and Animal Physiology
- Glioma Diagnosis and Treatment
- Mitochondrial Function and Pathology
- High Altitude and Hypoxia
- Peroxisome Proliferator-Activated Receptors
- Hemoglobin structure and function
- Forensic Fingerprint Detection Methods
University of California, San Francisco
2020-2024
Stanford University
2023
Chan Zuckerberg Initiative (United States)
2023
Washington University in St. Louis
2023
City College of San Francisco
2022
Andrija Stampar Teaching Institute of Public Health
2020-2021
Howard Hughes Medical Institute
2014-2019
University of California, Berkeley
2013-2019
California Institute for Regenerative Medicine
2018-2019
Sorbonne Université
2013
Treatment of solid cancers with chimeric antigen receptor (CAR) T cells is plagued by the lack ideal target antigens that are both absolutely tumor specific and homogeneously expressed. We show multi-antigen prime-and-kill recognition circuits provide flexibility precision to overcome these challenges in context glioblastoma. A synNotch recognizes a priming antigen, such as heterogeneous but tumor-specific glioblastoma neoantigen epidermal growth factor splice variant III (EGFRvIII) or...
Chimeric antigen receptor (CAR) costimulatory domains derived from native immune receptors steer the phenotypic output of therapeutic T cells. We constructed a library CARs containing ~2300 synthetic domains, built combinations 13 signaling motifs. These promoted diverse human cell fates, which were sensitive to motif and configurations. Neural networks trained decode combinatorial grammar CAR motifs allowed extraction key design rules. For example, non-native that bind tumor necrosis factor...
The conserved heat shock transcription factor–1 (HSF-1) is essential to cellular stress resistance and life-span determination. canonical function of HSF-1 regulate a network genes encoding molecular chaperones that protect proteins from damage caused by extrinsic environmental or intrinsic age-related deterioration. In Caenorhabditis elegans , we engineered modified strain increased longevity without enhanced chaperone induction. This health assurance acted through the regulation...
Integrating stress responses across tissues is essential for the survival of multicellular organisms. The metazoan nervous system can sense protein-misfolding arising in different subcellular compartments and initiate cytoprotective transcriptional periphery. Several possess a homotypic signal whereby respective compartment relies on single signaling mechanism to convey information within affected cell same stress-responsive pathway peripheral tissues. In contrast, we find that heat shock...
Anti-CD20 monoclonal antibody (mAb) B-cell depletion is a remarkably successful multiple sclerosis (MS) treatment. Chimeric antigen receptor (CAR)-T cells, which target antigens in non-major histocompatibility complex (MHC)-restricted manner, can penetrate tissues more thoroughly than mAbs. However, previous study indicated that anti-CD19 CAR-T cells paradoxically exacerbate experimental autoimmune encephalomyelitis (EAE) disease. We tested B-cell-dependent EAE model responsive to anti-CD20...
To engineer cells that can specifically target the central nervous system (CNS), we identified extracellular CNS-specific antigens, including components of CNS matrix and surface molecules expressed on neurons or glial cells. Synthetic Notch receptors engineered to detect these antigens were used program T induce expression diverse payloads only in brain. CNS-targeted induced chimeric antigen receptor efficiently cleared primary secondary brain tumors without harming cross-reactive outside...
Immune homeostasis requires a balance of inflammatory and suppressive activities. To design cells potentially useful for local immune suppression, we engineered conventional CD4 + T with synthetic Notch (synNotch) receptors driving antigen-triggered production anti-inflammatory payloads. Screening diverse library suppression programs, observed the strongest cytotoxic cell attack by both factors (interleukin-10, transforming growth factor–β1, programmed death ligand 1) sinks proinflammatory...
Abstract Background: While clinical trials involving chimeric antigen receptor (CAR) T cells have shown promise for treating pediatric brain tumors, factors such as heterogeneity, on-target, off-tumor toxicity and an immunosuppressive microenvironment limit the efficacy of these treatments. To overcome challenges, we adopted synthetic notch system developed innovative synNotch-CAR cell circuits. In this system, first which is expressed exclusively on brain, primes to locally induce...
A transient activation of the unfolded protein response ER is a key factor cellular reprogramming success.
Opioid tolerance is well-described physiologically but its mechanistic basis remains incompletely understood. An important site of opioid action in vivo the presynaptic terminal, where opioids inhibit transmitter release. This response characteristically resists desensitization over minutes yet becomes gradually tolerant hours, and how this possible unknown. Here, we delineate a cellular mechanism underlying longer-term form cultured rat medium spiny neurons. Our results support model which...
The main biologically active components of plants belonging to the genus Allium, responsible for their biological activities, including anti-inflammatory, antioxidant and immunomodulatory, are organosulfur compounds. aim this study was synthetize mixture dipropyl polysulfides (DPPS) test activity in acute hepatitis. C57BL/6 mice were administered orally with DPPS 6 h before intravenous injection Concanavalin A (ConA). Liver inflammation, necrosis hepatocytes apoptosis determined by...
ABSTRACT Treatment of solid cancers with chimeric antigen receptor (CAR) T cells is plagued by the lack target antigens that are both tumor-specific and homogeneously expressed. We show multiantigen prime-and-kill recognition circuits have flexibility precision to overcome these challenges in attacking glioblastoma. A synNotch recognizes a specific priming – heterogeneous glioblastoma neoantigen EGFRvIII or brain tissue-specific used locally induce expression CAR, enabling thorough but...
Abstract BACKGROUND Diffuse midline glioma (DMG), including intrinsic pontine (DIPG), is an aggressive brain tumor in children with limited treatment options. Recent developments of phase 1 clinical trials have shown early promise for chimeric antigen receptor (CAR) T cells patients DMG/DIPG. However, several barriers such as the absence tumor-specific antigens, restricted trafficking to site, and poor persistence hinder full therapeutic potential CAR cell therapy METHODS To safely target...
<h3>Background</h3> While clinical trials involving chimeric antigen receptor (CAR) T cells have shown promise for treating pediatric brain tumors that in trials, factors such as heterogeneity, on-target, off-tumor toxicity and an immunosuppressive microenvironment limit the efficacy of these treatments. To overcome challenges, we adopted synthetic notch system developed innovative synNotch-CAR cell circuits. In this system, first which is expressed exclusively on brain, primes to locally...
Abstract Copper serves as a limiting factor for multiple steps of tumour progression, including angiogenesis, growth and metastasis. High levels copper have been found in wide spectrum human cancers. Antitumour activities copper-chelating drugs reported animal models. Organosulfur compounds (diallyl sulfide, DAS; diallyl disulfide, DADS; S-ethylcysteine, SEC; N-acetylcysteine, NAC) derived from garlic exhibit marked activity. We analysed mixture fifteen n-propyl polysulfides (DPPS) potential...
ABSTRACT Chimeric antigen receptor (CAR) costimulatory domains steer the phenotypic output of therapeutic T cells. In most cases these are derived from native immune receptors, composed signaling motif combinations selected by evolution. To explore if non-natural motifs could drive novel cell fates interest, we constructed a library CARs containing ∼2,300 synthetic domains, built 13 peptide motifs. The produced driving diverse fate outputs, which were sensitive to and configurations. Neural...