17,837 results match your criteria: "The Scripps Research Institute.[Affiliation]"
Mol Cell Biol
November 2024
Department of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, California, USA.
Rab11 family interacting protein 4 (Rab11-FIP4) regulates endocytic trafficking. A possible role for Rab11-FIP4 in the regulation of lysosomal function has been proposed, but its precise function in the regulation of cellular homeostasis is unknown. By mRNA array and protein analysis, we found that Rab11-FIP4 is downregulated in the lysosomal storage disease cystinosis, which is caused by genetic defects in the lysosomal cystine transporter, cystinosin.
View Article and Find Full Text PDFProtein Sci
November 2024
Antibody Discovery and Protein Engineering, Merck Healthcare KGaA, Darmstadt, Germany.
J Am Chem Soc
October 2024
Carbohydrate-Based Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Widely distributed in nature, sulfated glycan epitopes play important roles in diverse pathophysiological processes. However, due to their structural complexity, the preparation of glycan epitopes with structurally defined sulfation patterns is challenging, which significantly hampers the detailed elucidation of their biological functions at the molecular level. Here, we introduce a strategy for site-specific chemical sulfation of glycan epitopes, leveraging enzymatic sialylation and desialylation processes to precisely control the regio-specificity of sulfation of disaccharide or trisaccharide glycan backbones.
View Article and Find Full Text PDFbioRxiv
October 2024
Department of Molecular and Cellular Biology, The Scripps Research Institute, California, United States.
Cancer treatment has been rapidly transformed by the development of immune checkpoint inhibitors targeting CTLA-4 and PD-1/PD-L1. However, many patients fail to respond, especially those with an immunosuppressive tumor microenvironment (TME), suggesting the existence of additional immune checkpoints that act through orthogonal mechanisms. Sialic acid-binding immunoglobulin-like lectin (Siglec)-7 and -9 are newly designated glycoimmune checkpoints that are abundantly expressed by tumor-infiltrating myeloid cells.
View Article and Find Full Text PDFMol Cell
November 2024
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address:
Pioneer transcription factors (TFs) bind to and open closed chromatin, facilitating engagement by other regulatory factors involved in gene activation or repression. Chemical probes are lacking for pioneer TFs, which has hindered their mechanistic investigation in cells. Here, we report the chemical proteomic discovery of electrophilic compounds that stereoselectively and site-specifically bind the pioneer TF forkhead box protein A1 (FOXA1) at a cysteine (C258) within the forkhead DNA-binding domain.
View Article and Find Full Text PDFCell Rep
October 2024
Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Kidney Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:
The kidneys act as finely tuned sensors to maintain physiological homeostasis. Both sympathetic and sensory nerves modulate kidney function through precise neural control. However, how the kidneys are innervated during development to support function remains elusive.
View Article and Find Full Text PDFJ Am Chem Soc
October 2024
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, United States.
Despite recent advances in ligand-enabled C(sp)-H functionalization of native substrates, controlling chemoselectivity in the presence of methyl and methylene C(sp)-H bonds remains a significant challenge. Herein, we report the first example of the Pd(II)-catalyzed chemoselective lactonization of γ-methyl and methylene C(sp)-H bonds of carboxylic acids. Exclusive chemoselectivity of methyl or methylene γ-lactonization was achieved by using two different classes of Quinoline-Pyridone ligands.
View Article and Find Full Text PDFTrends Pharmacol Sci
November 2024
Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA. Electronic address:
The impact of small molecules in human biology are manifold; not only are they critical regulators of physiological processes, but they also serve as probes to investigate biological pathways and leads for therapeutic development. Identifying the protein targets of small molecules, and where they bind, is critical to understanding their functional consequences and potential for pharmacological use. Over the past two decades, chemical proteomics has emerged as a go-to strategy for the comprehensive mapping of small molecule-protein interactions.
View Article and Find Full Text PDFCells
September 2024
Department of Pharmacology, University of California San Diego, CA 92093, USA.
Perineuronal nets (PNNs), a specialized form of extra cellular matrix (ECM), surround numerous neurons in the CNS and allow synaptic connectivity through holes in its structure. We hypothesize that PNNs serve as gatekeepers that guard and protect synaptic territory and thus may stabilize an engram circuit. We present high-resolution and 3D EM images of PNN-engulfed neurons in mice brains, showing that synapses occupy the PNN holes and that invasion of other cellular components is rare.
View Article and Find Full Text PDFEur Respir J
November 2024
The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
Curr Opin Struct Biol
December 2024
The Scripps Research Institute, Department of Integrative Structural and Computational Biology, La Jolla, CA, USA. Electronic address:
Pharmacol Res
November 2024
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA. Electronic address:
Epidemiological data indicate a strong association between alcohol use disorder (AUD) and neuropathic pain. Genetically-selected Marchigian Sardinian alcohol-preferring (msP) rats exhibit a high preference for alcohol compared with their background strain (Wistar rats), but their sensitivity to mechanical allodynia after chronic alcohol exposure is unknown. The present study compared the development of mechanical allodynia between "low, non-pathological drinker" Wistar rats and "high drinker" msP rats using the two-bottle choice (2BC) free-access procedure.
View Article and Find Full Text PDFAm J Epidemiol
October 2024
Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC; Carolina Population Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Development
October 2024
Department of Biochemistry, University of Cambridge, Hopkins Building, Downing Site, Tennis Court Road, Cambridge CB2 1QW, UK.
Nat Biotechnol
October 2024
Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
J Proteome Res
November 2024
Departments of Molecular Medicine and Neurobiology, the Scripps Research Institute, La Jolla 92037, California, United States.
Biophys J
November 2024
Computational Neurobiology Lab, The Salk Institute of Biological Studies, La Jolla, California; Department of Chemistry and Biochemistry, The University of California San Diego, La Jolla, California. Electronic address:
We present the first-ever, fully discrete, stochastic model of triggered cardiac Ca dynamics. Using anatomically accurate subcellular cardiac myocyte geometries, we simulate the molecular players involved in Ca handling using high-resolution stochastic and explicit-particle methods at the level of an individual cardiac dyadic junction. Integrating data from multiple experimental sources, the model not only replicates the findings of traditional in silico studies and complements in vitro experimental data but also reveals new insights into the molecular mechanisms driving cardiac dysfunction under stress and disease conditions.
View Article and Find Full Text PDFNat Commun
October 2024
Department of Molecular and Cell Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Cancer Immunol Res
January 2025
Department of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, California.
The histone methyltransferase enhancer of zeste homolog 2 (EZH2) plays important roles in T-cell differentiation, proliferation, and function. Previous studies have demonstrated that genetic deletion of EZH2 in CD8+ or total T cells impairs their antiviral and antitumor activities, cytokine production, and ability to expand upon rechallenge. Contrary to the detrimental role of deleting T cell-intrinsic EZH2, in this study, we demonstrated that transient inhibition of EZH2 in T cells prior to the phenotypic onset of exhaustion with a clinically approved inhibitor, tazemetostat (Taz), delayed their dysfunctional progression and preserved T-cell stemness and polyfunctionality but had no negative impact on cell proliferation.
View Article and Find Full Text PDFPLoS Pathog
October 2024
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Amsterdam, The Netherlands.
An effective human immunodeficiency virus 1 (HIV-1) vaccine will most likely have to elicit broadly neutralizing antibodies (bNAbs) to overcome the sequence diversity of the envelope glycoprotein (Env). So far, stabilized versions of Env, such as SOSIP trimers, have been able to induce neutralizing antibody (NAb) responses, but those responses are mainly strain-specific. Here we attempted to broaden NAb responses by using a multivalent vaccine and applying a number of design improvements.
View Article and Find Full Text PDFAm J Gastroenterol
October 2024
Division of Gastroenterology/Hepatology, Scripps Clinic.
Commun Biol
October 2024
Centre for Translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
The continuous emergence of SARS-CoV-2 variants of concern has rendered many therapeutic monoclonal antibodies (mAbs) ineffective. To date, there are no clinically authorized therapeutic antibodies effective against the recently circulating Omicron sub-lineages BA.2.
View Article and Find Full Text PDFAmyloid
December 2024
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SE, Sweden.
The ISA Nomenclature Committee met at the XIX International Symposium of Amyloidosis in Rochester, MN, 27 May 2024. The in-person event was followed by many electronic discussions, resulting in the current updated recommendations. The general nomenclature principles are unchanged.
View Article and Find Full Text PDFMol Psychiatry
September 2024
Neurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
MEF2C is a critical transcription factor in neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Despite prior animal studies of MEF2C heterozygosity to mimic MHS, MHS-specific mutations have not been investigated previously, particularly in a human context as hiPSCs afford. Here, for the first time, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits.
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