K. C. Garcia

Long-term single molecule localization microscopy uncovers dynamic co-assembly of Lrp6 and Ror2 into Wnt-signalosomes

This study uses single-molecule tracking to show that Lrp6 and Ror2 co-assemble into hybrid Wnt signalosomes dynamically.

A general platform for targeting MHC-II antigens via a single loop

This paper introduces TRACeR-II, a platform for developing MHC-II binders using a single loop, demonstrating its versatility and applicability to SARS-CoV-2 peptides.

IL-2-induced Stat3 Signaling is Critical for Effector Treg Cell Programming

This study identifies IL-2-induced Stat3 signaling as essential for programming iTreg cells to differentiate into eTreg cells and achieve IL-10 transcriptional competency.

De novo design of buttressed loops for sculpting protein functions

This paper designs proteins with structured loops supported by hydrogen bonds, demonstrating their stability and functionality in binding extended peptides.

AlphaFold2 enables accurate deorphanization of ligands to single-pass receptors

The paper uses AlphaFold2 to predict ligand-receptor interactions for single-pass transmembrane receptors with high accuracy.

FOXP3+ regulatory T cells use heparanase to access IL-2 bound to ECM in inflamed tissues

The paper shows FOXP3+ Treg use heparanase to access IL-2 bound to ECM in inflamed tissues, enhancing their function and stability.

Structural insight into guanylyl cyclase receptor hijacking of the kinase-Hsp90 regulatory mechanism

This study presents the cryo-EM structure of GC-C with Hsp90 and Cdc37, revealing how membrane receptor guanylyl cyclases use kinase-like Hsp90 regulatory mechanisms and informing therapeutic development.

Receptor Elimination by E3 Ubiquitin Ligase Recruitment (REULR): A Targeted Protein Degradation Toolbox

This paper introduces REULR, a nanobody-based degradation toolbox that enables targeted elimination of cell surface receptors by recruiting E3 ubiquitin ligases, demonstrating effective receptor clearance and modulation of signaling.

Structure of the Wnt-Frizzled-LRP6 initiation complex reveals the basis for co-receptor discrimination

The paper determines the structure of a ternary Wnt-Frizzled-LRP6 complex, revealing how co-receptor discrimination occurs through specific domains.

Induced CD45 Proximity Potentiates Natural Killer Cell Receptor Antagonism

This study shows that CD45-linked NKR antagonists enhance NK and T cell activity more than traditional antibodies, revealing potential for improved cancer immunotherapies.

Identification of orphan ligand-receptor relationships using a cell-based CRISPRa enrichment screening platform.

The paper develops a CRISPRa-based screening platform to identify orphan ligand-receptor interactions by screening secreted proteins against cell surface receptor libraries.

Biofunctional nanodot arrays in living cells uncover synergistic co-condensation of Wnt signalodroplets

The paper develops biofunctional nanodot arrays to study Wnt signalodroplets in live cells, revealing synergistic co-condensation through liquid-liquid phase separation.

Structure of the IL-27 quaternary receptor signaling complex

The paper determines the structure of the IL-27 receptor signaling complex using cryo-EM, revealing a unique three-site assembly mechanism distinct from related cytokines.

Powerful synergistic effects of a STING agonist and an IL-2 superkine in cancer immunotherapy against MHC I-deficient and MHC I+ tumors

The paper combines a STING agonist and an IL-2 superkine to enhance cancer immunotherapy, showing efficacy against both MHC I-deficient and MHC I+ tumors.

Membrane phosphoinositides stabilize GPCR-arrestin complexes and offer temporal control of complex assembly and dynamics

This study identifies membrane phosphoinositides as regulators of GPCR-arrestin complex dynamics, showing they stabilize complexes and enable temporal control of receptor signaling and recycling.

Structure-activity mapping of the force- and sequence-dependent landscape of T cell activation

This paper introduces BATTLES, a high-throughput method that applies biomechanical force to screen pMHCs for T-cell activation, revealing force- and sequence-dependent responses.

Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures

This paper develops a feeder-free organoid culture system for human distal lung progenitors and demonstrates SARS-CoV-2 infection of club cells in a novel in vitro model.

Interleukin-2 druggability is modulated by global conformational transitions controlled by a helical capping switch

This study identifies a helical capping switch in IL-2 that modulates its conformational transitions and drug interactions, providing a framework for designing precision therapeutics.

Facile method for screening clinical T cell receptors for off-target peptide-HLA reactivity

The paper develops a yeast-display platform to screen TCRs for off-target peptide-HLA reactivity, identifying clinical toxicity associated with an affinity-matured TCR.

Differential induction of interferon stimulated genes between type I and type III interferons is independent of interferon receptor abundance

This paper shows that type I and III interferons induce interferon stimulated genes with different kinetics, and these differences are intrinsic to the signaling pathways, not receptor abundance.

A Polymorphic Residue That Attenuates the Antiviral Potential of Interferon Lambda 4 in Hominid Lineages

The paper identifies a polymorphic residue in IFN{lambda}4 that reduces its antiviral activity in humans compared to other hominids, contributing to differences in HCV clearance.

In vitro reconstitution of T cell receptor-mediated segregation of the CD45 phosphatase

This paper demonstrates that TCR-pMHC and PD-1-PD-L1 interactions can exclude CD45 from membrane interfaces, creating spatial organization that may regulate T cell signaling.