A5085681852- CAR-T cell therapy research
- Venomous Animal Envenomation and Studies
- Microtubule and mitosis dynamics
- Nanowire Synthesis and Applications
- Nicotinic Acetylcholine Receptors Study
- Ion channel regulation and function
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- Photosynthetic Processes and Mechanisms
- Nanofabrication and Lithography Techniques
- Monoclonal and Polyclonal Antibodies Research
- Protist diversity and phylogeny
- Viral Infectious Diseases and Gene Expression in Insects
- Statistics Education and Methodologies
- Healthcare and Venom Research
- Toxin Mechanisms and Immunotoxins
- vaccines and immunoinformatics approaches
- Advanced Electron Microscopy Techniques and Applications
- Ectopic Pregnancy Diagnosis and Management
- Electrochemical sensors and biosensors
- Plant Molecular Biology Research
- Genomics and Phylogenetic Studies
- bioluminescence and chemiluminescence research
- Urinary and Genital Oncology Studies
- Surfactants and Colloidal Systems
Stanford University
2023-2025
Cancer Prevention Institute of California
2023
Stanford Cancer Institute
2023
Chan Zuckerberg Initiative (United States)
2023
University of California, San Francisco
2019-2022
University of California, San Diego
2021
Howard Hughes Medical Institute
2021
Marine Biological Laboratory
2015
Universidad Nacional Autónoma de México
2009-2014
Harvard University
2011-2012
Designing smarter anticancer T cells Biological signaling systems can exhibit a large, nonlinear—or “ultrasensitive”—response, which would be useful to engineer into therapeutic allow for better discrimination between cancer and normal tissues. Hernandez-Lopez et al. modified human using two-step mechanism that allowed them kill expressing large amounts of marker protein but not small amount the same protein. A first synthetic receptor recognized antigen with low affinity. That signaled...
Cytoplasmic dynein is a microtubule-based motor required for intracellular transport and cell division. Its movement involves coupling cycles of track binding release with force-generating nucleotide hydrolysis. How this accomplished given the ~25 nanometers separating dynein's track- nucleotide-binding sites not understood. Here, we present subnanometer-resolution structure microtubule-binding domain bound to microtubules by cryo-electron microscopy that was used generate pseudo-atomic...
Abstract Engineered T cell therapies have emerged as a promising approach for cancer treatment, yet their application to solid tumors remains challenging due the limited specificity and persistence of current antigen recognition strategies. Here, we introduced sherpabodies, engineered from human SH3 domain scaffold, class antibody-mimetic proteins capable precise tumor-associated recognition. A phage display library identified sherpabodies against panel popular antigens (TAA), which were...
Animal venoms are rich sources of ligands for studying ion channels and other pharmacological targets. Proteomic analyses the soluble venom from Mexican scorpion Vaejovis mexicanus smithi showed that it contains more than 200 different components. Among them, a 36-residue peptide with molecular mass 3864 Da (named Vm24) was shown to be potent blocker Kv1.3 human lymphocytes (Kd ∼ 3 pM). The three-dimensional solution structure Vm24 determined by nuclear magnetic resonance, showing folds into...
Abstract Enzymes that oxidize aromatic substrates have shown utility in a range of cell-based technologies including live cell proximity labeling (PL) and electron microscopy (EM), but are associated with drawbacks such as the need for toxic H 2 O . Here, we explore laccases novel enzyme class PL EM mammalian cells. LaccID, generated via 11 rounds directed evolution from an ancestral fungal laccase, catalyzes one-electron oxidation diverse using instead , exhibits activity selective to...
Identifying highly specific T cell receptors (TCRs) or antibodies against epitopic peptides presented by class I major histocompatibility complex (MHC I) proteins remains a bottleneck in the development of targeted therapeutics. Here, we introduce recognition antigen–MHC reporter for MHC (TRACeR-I), generalizable platform targeting on polymorphic HLA-A*, HLA-B* and HLA-C* allotypes while overcoming cross-reactivity challenges TCRs. Our TRACeR–MHC co-crystal structure reveals unique antigen...
The scorpion toxin tamapin displays the most potent and selective blockage against KCa2.2 channels known to date. In this work, we report biosynthesis, three-dimensional structure, cytotoxicity on cancer cell lines (Jurkat E6-1 human mammary breast MDA-MB-231) of recombinant five related peptides bearing mutations residues (R6A,R7A, R13A, R6A-R7A, GS-tamapin) that were previously suggested be important for tamapin's activity. indicated used as they constitutively express channels. studied...
Abstract The microtubule (MT) cytoskeleton is central to cellular processes including axonal growth, intracellular transport, and cell division, all of which rely on precise spatiotemporal control MT organization. Kinesin-8s play a key role in regulating length by combining highly processive directional motility with MT-end disassembly. However, how kinesin-8 switches between these two apparently opposing activities remains unclear. Here, we define the structural features underlying this...
Abstract Overexpressed tumor associated antigens (e.g. HER2 and EGFR) are attractive targets for therapeutic T cells, but toxic cross-reaction with normal tissues expressing low antigen levels has been observed Chimeric Antigen Receptor (CAR) cells targeting such antigens. Inspired by natural ultrasensitive response circuits, we engineer a two-step positive feedback circuit that allows to discriminate based on sigmoidal density threshold. In this circuit, affinity SynNotch receptor controls...
In this Minding the Future column piece, a team from Mexico describe their efforts in moving data science program for high school and college students online during COVID-19 pandemic.The piece highlights both flexibility required of educators at height pandemic, to which many went ensure that educational opportunities continued, some cases even expanded.Statisticians scientists had-and continue have-a key role explaining abundance collected global as well clarifying what could (and not) tell us.
Abstract T-cells can be redirected to kill tumor cells via synthetic T-cell receptors known as chimeric antigen (CARs); this approach is becoming a highly promising therapeutic strategy for cancer treatment. Current CAR T-cells, while effective at killing expressing the target antigen, fail discriminate between high and low levels of common antigens. Potential antigens are often also found on normal lower expression levels, get activated even by amounts resulting in potentially deadly toxic...