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Articles by Birgit Schilling
Gemfibrozil promotes longevity and health by restricting amino acid uptake through the Dipeptide transporter, PEPT1
Abstract The FDA-approved fibrate, gemfibrozil, has been used clinically to treat hyperlipidaemia, showing efficacy both in lowering triglycerides and increasing high-density lipoproteins. However, in recent years, the drug has been increasingly investigated for potential clinical use in other diseases. Here, we show for the first time that gemfibrozil promotes healthy lifespan across multiple evolutionarily diverse species.
γδ T cell-stromal networks modulate matrix composition and vascularity in foreign body response
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Abstract Immune-stromal crosstalk governs tissue fibrosis, which is marked by dysregulated extracellular matrix (ECM) production and aberrant vasculature. Here, we investigate how γδ T cell interactions with stromal cells shape fibrosis in the foreign body response in a murine biomaterial implant model. During the acute reaction, type-1 (γδIFNγ) and type-17 (γδ17) γδ T cell subsets accumulate at the implant site.
By Anna Ruta, Kavita Krishnan, Jiwon Woo, Joscelyn C. Mejias, Elise Gray-Gaillard, David R. Jr., Helen Nguyen, Helen Nguyễn, Alexandra Rindone, Christopher Cherry, Michael Patatanian, Frank Yu, Brenda Yang, Connor D. Amelung, Christina King, Birgit Schilling, Sharon Gerecht, Elana Fertig, Locke Davenport Huyer, Drew Pardoll, Jennifer H. Elisseeff
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Nature
Verified
iCLAP: an innovative method for integrable co-detection of low-abundance antigens with high-plex immunostaining - Nature Communications
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Abstract Multiplexed protein imaging enables spatial analysis of complex tissues, but detecting proteins expressed at low levels remains challenging, particularly in widely available formalin-fixed, paraffin-embedded (FFPE) specimens. Many biologically important regulators—including senescence markers, transcription factors, and secreted proteins—are therefore difficult to study in situ using existing high-plex methods.
By Fan Wu, Shuyuan Zheng, Yani Chen, Peijia Ye, Moo Joong Kim, Seojin Lee, Geroge Kuo, Shriya Pillan, Ruihan Yuan, Bofei Yu, Qingfeng Zhu, Sarah Shin, Courtney Cannon, Gabriele Pierre, Kanako Iwasaki, Cristina Aguayo-Mazzucato, Nicolas Musi, George A. Kuchel, Birgit Schilling, Laura Wood, Won Jin Ho, Robert A. Anders, Denis Wirtz, Pei-Hsun Wu
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Nature
Verified
Advancing biological understanding of cellular senescence with computational multiomics - Nature Genetics
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Abstract Cellular senescence is a complex biological process that plays a pathophysiological role in aging and age-related diseases. The biological understanding of senescence at the cellular and tissue levels remains incomplete due to the lack of specific biomarkers as well as the relative rarity of senescent cells, their phenotypic heterogeneity and dynamic features.
By Michael J. Becich, Elana Fertig, Liangcai Gu, Qianjiang Hu, Zhicheng Ji, Nathan K. LeBrasseur, Anjun Ma, Qin Ma, Vilas Menon, Jacob Mitchell, Laura J. Niedernhofer, Mauricio Rojas, Siyuan Wang, Pei-Hsun Wu, Ming Xu, Miao Yu, Xu Zhang, Peter Adams, Darren Baker, Christopher Benz, Bennett G. Childs, Jeffrey H. Chuang, Dongjun Chung, Mingze Dong, William F. Flynn, David Furman, Stephanie Halene, Ann V Hertzel, Kanako Iwasaki, James Kirkland, Ron Korstanje, Yang Liu Verified, Helene Martini, Simon Melov, João F. Passos, Alexandra Rindone, Paul D. Robbins, Paul Robson, Jhonny Rodriguez-Lopez, Nadia A. Rosenthal, Marissa J. Schafer, Birgit Schilling, Elizabeth Schmidt, Tamar Tchkonia, Marcos G. Teneche, Natalia Vanegas, Rong Fan
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Nature
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Amyloid-β-driven Alzheimer’s disease reshapes the colonic immune system in mice
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Keywords Alzheimer’s disease gut-brain axis mucosal immunity plasma cells B cells neuroimmunology dietary intervention immunometabolism chemokine axis CXCR4 Research topic(s) CP: Neuroscience CP: Immunology Introduction Late-onset Alzheimer’s disease (AD) primarily occurs in individuals over the age of 65 years, presents with symptoms of dementia and anxiety, and is more prevalent in females.1 The neuropathology of AD involves an early pre-symptomatic period that correlates with extracellular...
By Priya Makhijani, Taylor R Valentino, Rohini Emani, Wei-Chieh Mu, Carlos Aguirre, Christopher Tan, Anand Rane, Kenneth Wilson, Nan Chen, Huixun Du, Benjamin Ambrose, Saad Khan, Shawn Winer, Chao Wang, Arthur Mortha, David Furman, Birgit Schilling, Lisa M. Ellerby, Olga Rojas, Julie Andersen, Daniel A. Winer, Max Manwaring-Mueller, Alexander Kifle
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Cell Reports
Verified
Neuronal glycogen breakdown mitigates tauopathy via pentose-phosphate-pathway-mediated oxidative stress reduction - Nature Metabolism
Abstract Tauopathies encompass a range of neurodegenerative disorders, such as Alzheimer’s disease (AD) and frontotemporal lobar degeneration with tau inclusions (FTLD-tau), for which there are currently no successful treatments. Here, we show impaired glycogen metabolism in the brain of a tauopathy Drosophila melanogaster model and people with AD, indicating a link between tauopathies and glycogen metabolism.
Challenges and recommendations for the translation of biomarkers of aging - Nature Aging
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Abstract Biomarkers of aging (BOA) are quantitative parameters that predict biological age and ideally its changes in response to interventions. In recent years, many promising molecular and omic BOA have emerged with an enormous potential for translational geroscience and improving healthspan. However, clinical translation remains limited, in part due to the gap between preclinical research and the application of BOA in clinical research and other translational settings.
By Jesse R. Poganik, Daniel Belsky, Joe LaCroix Verified, Alan Cohen, Steven R. Cummings, Luigi Ferrucci, David Furman, Albert T. Higgins-Chen, Steve Horvath, Jamie Justice, Douglas P Kiel, George A. Kuchel, Jessica Lasky-Su, Nathan K. LeBrasseur, Andrea B. Maier, Birgit Schilling, Vittorio Sebastiano, P. Eline Slagboom, Michael Snyder, Eric Verdin, Alex Zhavoronkov
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Nature
Verified
SenNet recommendations for detecting senescent cells in different tissues - Nature Reviews Molecular Cell Biology
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Abstract Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest.
By Vidyani Suryadevara, Adam D. Hudgins, Alberto Pappalardo, Alla Karpova, Amit K. Dey, Birgit Schilling, Cristina Aguayo-Mazzucato, Darren Baker, Diana Jurk, Elizabeth Schmidt, George A. Kuchel, Jonathan Silverstein, Kanako Iwasaki, Karina O Barbosa, Madison L. Doolittle, Marissa J. Schafer, Ming Xu, Mozhgan Boroumand, Paul Robson, Peter Adams, Ramalakshmi Ramasamy, Rong Fan, Ruth R. Montgomery, Sundeep Khosla, Yizhe Song, Helene Martini, Marcos G. Teneche, Periklis Vasilikos, Rolando Perez-Lorenzo
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Nature
Verified
Regulation of urea cycle by reversible high-stoichiometry lysine succinylation - Nature Metabolism
Abstract The post-translational modification lysine succinylation is implicated in the regulation of various metabolic pathways. However, its biological relevance remains uncertain due to methodological difficulties in determining high-impact succinylation sites. Here, using stable isotope labelling and data-independent acquisition mass spectrometry, we quantified lysine succinylation stoichiometries in mouse livers.
Aging impairs the osteocytic regulation of collagen integrity and bone quality - Bone Research
Abstract Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties.
OXR1 maintains the retromer to delay brain aging under dietary restriction - Nature Communications
Abstract Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids.
Senescent cells perturb intestinal stem cell differentiation through Ptk7 induced noncanonical Wnt and YAP signaling - Nature Communications
Abstract Cellular senescence and the senescence-associated secretory phenotype (SASP) are implicated in aging and age-related disease, and SASP-related inflammation is thought to contribute to tissue dysfunction in aging and diseased animals. However, whether and how SASP factors influence the regenerative capacity of tissues remains unclear.
PTM Site Localization And Isomer Differentiation Of Phosphorylated Peptides
By Joanna Bons, Jason Cason, Birgit Schilling, and Christie Hunter Protein phosphorylation is an important post-translational modification (PTM) as it is involved in a large variety of dynamic cellular processes. However, PTM site localization and quantification of phosphopeptides by collision induced dissociation (CID) MS/MS can be challenging, and phospho-peptides can exhibit a partial neutral loss of the phospho group (-98 Th).
PTM Site Localization And Isomer Differentiation Of Phosphorylated Peptides
By Joanna Bons, Jason Cason, Birgit Schilling, and Christie Hunter Protein phosphorylation is an important post-translational modification (PTM) as it is involved in a large variety of dynamic cellular processes. However, PTM site localization and quantification of phosphopeptides by collision induced dissociation (CID) MS/MS can be challenging, and phospho-peptides can exhibit a partial neutral loss of the phospho group (-98 Th).
Dietary restriction and the transcription factor clock delay eye aging to extend lifespan in Drosophila Melanogaster - Nature Communications
Abstract Many vital processes in the eye are under circadian regulation, and circadian dysfunction has emerged as a potential driver of eye aging. Dietary restriction is one of the most robust lifespan-extending therapies and amplifies circadian rhythms with age. Herein, we demonstrate that dietary restriction extends lifespan in Drosophila melanogaster by promoting circadian homeostatic processes that protect the visual system from age- and light-associated damage.
Tunable Electron Activated Dissociation (EAD) MS/MS To Preserve Particularly Labile Post-Translational Modifications
By Joanna Bons, Jason Cason, Birgit Schilling, and Christie Hunter Post-translational modifications (PTMs) are important players in a diverse group of functions that include protein conformation and signaling. Lysine acylation, such as malonylation, is one such PTM, and is regulated in part by lysine deacylases, which are members of the sirtuin (SIRT) protein family.
Tunable Electron Activated Dissociation (EAD) MS/MS To Preserve Particularly Labile Post-Translational Modifications
By Joanna Bons, Jason Cason, Birgit Schilling, and Christie Hunter Post-translational modifications (PTMs) are important players in a diverse group of functions that include protein conformation and signaling. Lysine acylation, such as malonylation, is one such PTM, and is regulated in part by lysine deacylases, which are members of the sirtuin (SIRT) protein family.
Accumulation of ‘Old Proteins’ and the Critical Need for Mass Spectrometry based Protein Turnover Measurements in Aging and Longevity - Basisty - - PROTEOMICS - Wiley Online Library
Review Accumulation of ‘Old Proteins’ and the Critical Need for Mass Spectrometry based Protein Turnover Measurements in Aging and Longevity Birgit Schilling This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record.
Global Lysine Acetylation in Escherichia coli Results from Growth Conditions That Favor Acetate Fermentation
Research Article Birgit Schilling, Nathan Basisty, David G. Christensen, Dylan Sorensen, James S. Orr, Alan J. Wolfe, Christopher V. Rao Ann M. Stock, Editor DOI: 10.1128/JB.00768-18 ABSTRACT Lysine acetylation is thought to provide a mechanism for regulating metabolism in diverse bacteria. Indeed, many studies have shown that the majority of enzymes involved in central metabolism are acetylated and that acetylation can alter enzyme activity.
Global lysine acetylation in Escherichia coli results from growth conditions that favor acetate fermentation
Research Article Birgit Schilling, Nathan Basisty, David G. Christensen, Dylan Sorensen, James S. Orr, Alan J. Wolfe, Christopher V. Rao DOI: 10.1128/JB.00768-18 ABSTRACT Lysine acetylation is thought to provide a mechanism for regulating metabolism in diverse bacteria. Indeed, many studies have shown that the majority of enzymes involved in central metabolism are acetylated and that acetylation can alter enzyme activity.
Quantification of Site-specific Protein Lysine Acetylation and Succinylation Stoichiometry Using Data-independent Acquisition Mass Spectrometry
N -acylation of protein lysine residues is an important regulator of protein function. Lysine acetylation and other acylations, such as succinylation, malonylation, and glutarylation, are thought to regulate metabolism, cell signaling, and other cellular processes1,2,3,4, and have implications in metabolic disorders5.
Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry
To assess the inter- and intra-laboratory reproducibility and performance of SWATH-MS for large-scale quantitative proteomics, we created a benchmarking sample set and distributed aliquots to 11 laboratories worldwide (Fig 1a). The sample consisted of 30 stable isotope-labeled standard (SIS) peptides48 diluted into a complex background consisting of 1?µg of protein digest from HEK293 cells.
Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4
Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown.
Gadd45a Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4
Author contributions: SAB coordinated the experiments and performed them with invaluable contributions from SS, MCD, JMD, SME and ADD. BS and BWG performed the mass spectrometry analyses. CMA conceived the study, designed the experiments, and wrote the paper. All authors reviewed the results, contributed to data analysis and manuscript preparation, and approved the final version of the manuscript.
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