
Research Interests: Signal transduction, synthetic biology, systems biology, structural biology, protein-protein interactions, cell motility, MAP kinase cascades, GTPase pathways Summary: Wendell Lim's Lab is working on creating a detailed instruction manual - a sort of user's guide - that explains how biochemical circuits control a cell's function and ultimately its fate. The long-term goal is to use the instruction manual to help scientists design cells to deliver therapeutic payloads, repair cancerous lesions, or attack microscopic pathogens. Cells are complex mechanical and sensing devices that can carry out highly complex tasks, such as secreting antibodies or forming repair structures like blood clots and bone. Cells contain signaling pathways that take in and integrate vast amounts of information about the cells' environment, and they process and use this information to make complex decisions about how to respond to changing environmental conditions. If more is understood about how these processes work, there is the potential to change cells and help solve problems in biotechnology or health, and to treat disease more rationally.
Publications
Programmable microparticles rewire CAR signaling to enable super-physiological expansion of human T cells in vitro.
Engineered SH3-Derived Sherpabodies Function as a Modular Platform for Targeted T-cell Immunotherapy.
Abstract 6114: Engineering novel synNotch CAR T cells to precisely and effectively target medulloblastoma.
Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs.
Programming tissue-sensing T cells that deliver therapies to the brain.
De novo-designed minibinders expand the synthetic biology sensing repertoire.
Degron-Based bioPROTACs for Controlling Signaling in CAR T Cells.
DIPG-15. NOVEL CNS SENSING SYNNOTCH-CAR T CELLS FOR TARGETING DIFFUSE MIDLINE GLIOMA.
Degron-based bioPROTACs for controlling signaling in CAR T cells.
The General Characteristics and Design Taxonomy of Chatbots for COVID-19: A Systematic Review.
Golden age of immunoengineering.
An immune-based tool platform for in vivo cell clearance.
Instructional materials that control cellular activity through synthetic Notch receptors.
CAR-T Cell-Mediated B-Cell Depletion in Central Nervous System Autoimmunity.
Synthetic cytokine circuits that drive T cells into immune-excluded tumors.
Decoding CAR T cell phenotype using combinatorial signaling motif libraries and machine learning.
The emerging era of cell engineering: Harnessing the modularity of cells to program complex biological function.
Rethinking cancer targeting strategies in the era of smart cell therapeutics.
Deep-learning-based analysis of combinatorial synthetic T-cell receptor libraries.
Precise control of immune modulation using DNA scaffold-mediated biomaterial functionalization.
SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma.
T cells selectively filter oscillatory signals on the minutes timescale.
T cell circuits that sense antigen density with an ultrasensitive threshold.
DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation.
Engineering cytokines and cytokine circuits.
Precise T cell recognition programs designed by transcriptionally linking multiple receptors.
Engineering synthetic morphogen systems that can program multicellular patterning.
What is the Optimal Design-Build-Test Cycle for Clinically Relevant Synthetic CAR T Cell Therapies?
DNA-scaffolded biomaterials enable modular and tunable presentation of proteins to control immune cell therapies.
Engineering T Cells to Treat Cancer: The Convergence of Immuno-Oncology and Synthetic Biology.
IMMU-21. SEQUENTIAL TWO-RECEPTOR PRIMING CAR SYSTEM TO OVERCOME HETEROGENEOUS ANTIGEN EXPRESSION.
The Design Principles of Biochemical Timers: Circuits that Discriminate between Transient and Sustained Stimulation.
High-throughput multicolor optogenetics in microwell plates.
Engineering cell-cell communication networks: programming multicellular behaviors.
Synthetic Development: Learning to Program Multicellular Self-Organization.
Abstract A031: Engineering antigen density sensors for T-cell immunotherapy.
IMMU-57. SEQUENTIAL TWO-RECEPTOR PRIMING CAR SYSTEM TO OVERCOME HETEROGENEOUS ANTIGEN EXPRESSION.
Cancer mutations and targeted drugs can disrupt dynamic signal encoding by the Ras-Erk pathway.
Programming self-organizing multicellular structures with synthetic cell-cell signaling.
Tracing Information Flow from Erk to Target Gene Induction Reveals Mechanisms of Dynamic and Combinatorial Control.
Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells.
Interrogating cellular perception and decision making with optogenetic tools.
Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials.
Engineering dynamical control of cell fate switching using synthetic phospho-regulons.
Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors.
Cellular perception and misperception: Internal models for decision-making shaped by evolutionary experience.
Modular engineering of cellular signaling proteins and networks.
CRISPR/Cas9 for Human Genome Engineering and Disease Research.
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells.
Expanding the CRISPR imaging toolset with Staphylococcus aureus Cas9 for simultaneous imaging of multiple genomic loci.
Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation.
Oscillatory stress stimulation uncovers an Achilles' heel of the yeast MAPK signaling network.
Remote control of therapeutic T cells through a small molecule-gated chimeric receptor.
Synthetic biology approaches to engineer T cells.
Differential genetic interactions of yeast stress response MAPK pathways.
Specific gene repression by CRISPRi system transferred through bacterial conjugation.
Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal.
Exploitation of latent allostery enables the evolution of new modes of MAP kinase regulation (609.5).
Secreting and sensing the same molecule allows cells to achieve versatile social behaviors.
Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module.
Genetic sensor for strong methylating compounds.
Actin dynamics rapidly reset chemoattractant receptor sensitivity following adaptation in neutrophils.
Counting molecules in single organelles with superresolution microscopy allows tracking of the endosome maturation trajectory.
Signalling change: signal transduction through the decades.
Cell-based therapeutics: the next pillar of medicine.
Bridging cross-cultural gaps in scientific exchange through innovative team challenge workshops.
Design principles of regulatory networks: searching for the molecular algorithms of the cell.
Probing Molecular Number Variability in Intracellular Structures using Photoswitchable Fluorescent Proteins.
Cell biology 2.0.
Wendell Lim: exploring the path not chosen. Interview by Caitlin Sedwick.
The first World Cell Race.
Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation.
SYNZIP protein interaction toolbox: in vitro and in vivo specifications of heterospecific coiled-coil interaction domains.
Control of protein signaling using a computationally designed GTPase/GEF orthogonal pair.
A Light-Based Feedback Control System for Generating User-Defined Intracelullar Signaling Dynamics.
Recruitment interactions can override catalytic interactions in determining the functional identity of a protein kinase.
Scaffold proteins: hubs for controlling the flow of cellular information.
Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells.
Light control of plasma membrane recruitment using the Phy-PIF system.
The promise of optogenetics in cell biology: interrogating molecular circuits in space and time.
Build life to understand it.
Designing customized cell signalling circuits.
Rapid diversification of cell signaling phenotypes by modular domain recombination.
Defining network topologies that can achieve biochemical adaptation.
The Design Logic of Cell Signaling Systems.
Deciphering protein kinase specificity through large-scale analysis of yeast phosphorylation site motifs.
Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems.
A reciprocal interdependence between Nck and PI(4,5)P(2) promotes localized N-WASp-mediated actin polymerization in living cells.
Scaffolds: interaction platforms for cellular signalling circuits.
Positive selection of tyrosine loss in metazoan evolution.
Evolution of phosphoregulation: comparison of phosphorylation patterns across yeast species.
Frederic M Richards 1925-2009.
The Modular Logic of Cell Signaling Systems.
Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages.
Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics.
A microfluidic system for dynamic yeast cell imaging.
Synthetic biology: lessons from the history of synthetic organic chemistry.
Engineering synthetic signaling proteins with ultrasensitive input/output control.
Engineering modular protein interaction switches by sequence overlap.
Multiple WASP-interacting protein recognition motifs are required for a functional interaction with N-WASP.
Beta strand peptidomimetics as potent PDZ domain ligands.
Docking interactions in protein kinase and phosphatase networks.
The Modular Logic of Cell Signaling Systems.
The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway.
Domains, motifs, and scaffolds: the role of modular interactions in the evolution and wiring of cell signaling circuits.
The role of docking interactions in mediating signaling input, output, and discrimination in the yeast MAPK network.
A general model for preferential hetero-oligomerization of LIN-2/7 domains: mechanism underlying directed assembly of supramolecular signaling complexes.
Rewiring cell signaling: the logic and plasticity of eukaryotic protein circuitry.
Sho1 and Pbs2 act as coscaffolds linking components in the yeast high osmolarity MAP kinase pathway.
Reprogramming control of an allosteric signaling switch through modular recombination.
Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT.
The structure and function of proline recognition domains.
Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms.
Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function.
Coordinated folding and association of the LIN-2, -7 (L27) domain. An obligate heterodimerization involved in assembly of signaling and cell polarity complexes.
How signaling proteins integrate multiple inputs: a comparison of N-WASP and Cdk2.
From folding towards function.
From folding towards function.
The modular logic of signaling proteins: building allosteric switches from simple binding domains.
Structure of the SH3-guanylate kinase module from PSD-95 suggests a mechanism for regulated assembly of MAGUK scaffolding proteins.
Mechanism and role of PDZ domains in signaling complex assembly.
The double life of PX domains.
An analysis of the interactions between the Sem-5 SH3 domain and its ligands using molecular dynamics, free energy calculations, and sequence analysis.
Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex.
Converging on proline: the mechanism of WW domain peptide recognition.
Improving SH3 domain ligand selectivity using a non-natural scaffold.
PSD-95 assembles a ternary complex with the N-methyl-D-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain.
Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex.
Exploiting the basis of proline recognition by SH3 and WW domains: design of N-substituted inhibitors.
How Src exercises self-restraint.
Reading between the lines: SH3 recognition of an intact protein.
Structural determinants of peptide-binding orientation and of sequence specificity in SH3 domains.
Stability and peptide binding affinity of an SH3 domain from the Caenorhabditis elegans signaling protein Sem-5.
Critical residues in an SH3 domain from Sem-5 suggest a mechanism for proline-rich peptide recognition.
The crystal structure of a mutant protein with altered but improved hydrophobic core packing.
An analysis of packing in the protein folding problem.
The role of internal packing interactions in determining the structure and stability of a protein.
Analysis of DNA-protein interactions by affinity coelectrophoresis.
Random mutagenesis of protein sequences using oligonucleotide cassettes.
Deciphering the message in protein sequences: tolerance to amino acid substitutions.
Please update your Location In, Rm 001
UCSF Box 2280
Varies, CA 00001
United States