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635 results on '"Ueberheide, Beatrix"'

13. CDK-independent role of D-type cyclins in regulating DNA mismatch repair

Author

Rona, Gergely, Miwatani-Minter, Bearach, Zhang, Qingyue, Goldberg, Hailey V., Kerzhnerman, Marc A., Howard, Jesse B., Simoneschi, Daniele, Lane, Ethan, Hobbs, John W., Sassani, Elizabeth, Wang, Andrew A., Keegan, Sarah, Laverty, Daniel J., Piett, Cortt G., Pongor, Lorinc S., Xu, Miranda Li, Andrade, Joshua, Thomas, Anish, Sicinski, Piotr, Askenazi, Manor, Ueberheide, Beatrix, Fenyö, David, Nagel, Zachary D., and Pagano, Michele

Published
2024
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14. Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM

Author

Lanz, Tobias V, Brewer, R Camille, Ho, Peggy P, Moon, Jae-Seung, Jude, Kevin M, Fernandez, Daniel, Fernandes, Ricardo A, Gomez, Alejandro M, Nadj, Gabriel-Stefan, Bartley, Christopher M, Schubert, Ryan D, Hawes, Isobel A, Vazquez, Sara E, Iyer, Manasi, Zuchero, J Bradley, Teegen, Bianca, Dunn, Jeffrey E, Lock, Christopher B, Kipp, Lucas B, Cotham, Victoria C, Ueberheide, Beatrix M, Aftab, Blake T, Anderson, Mark S, DeRisi, Joseph L, Wilson, Michael R, Bashford-Rogers, Rachael JM, Platten, Michael, Garcia, K Christopher, Steinman, Lawrence, and Robinson, William H

Subjects
Brain Disorders, Clinical Research, Neurosciences, Infectious Diseases, Biotechnology, Multiple Sclerosis, Neurodegenerative, Genetics, Autoimmune Disease, 2.1 Biological and endogenous factors, Aetiology, Neurological, Animals, B-Lymphocytes, Cell Adhesion Molecules, Neuron-Glia, Epstein-Barr Virus Infections, Epstein-Barr Virus Nuclear Antigens, Herpesvirus 4, Human, Humans, Mice, Nerve Tissue Proteins, General Science & Technology
Abstract

Multiple sclerosis (MS) is a heterogenous autoimmune disease in which autoreactive lymphocytes attack the myelin sheath of the central nervous system. B lymphocytes in the cerebrospinal fluid (CSF) of patients with MS contribute to inflammation and secrete oligoclonal immunoglobulins1,2. Epstein-Barr virus (EBV) infection has been epidemiologically linked to MS, but its pathological role remains unclear3. Here we demonstrate high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM) and provide structural and in vivo functional evidence for its relevance. A cross-reactive CSF-derived antibody was initially identified by single-cell sequencing of the paired-chain B cell repertoire of MS blood and CSF, followed by protein microarray-based testing of recombinantly expressed CSF-derived antibodies against MS-associated viruses. Sequence analysis, affinity measurements and the crystal structure of the EBNA1-peptide epitope in complex with the autoreactive Fab fragment enabled tracking of the development of the naive EBNA1-restricted antibody to a mature EBNA1-GlialCAM cross-reactive antibody. Molecular mimicry is facilitated by a post-translational modification of GlialCAM. EBNA1 immunization exacerbates disease in a mouse model of MS, and anti-EBNA1 and anti-GlialCAM antibodies are prevalent in patients with MS. Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.

Published
2022

23. ORF10–Cullin-2–ZYG11B complex is not required for SARS-CoV-2 infection

Author

Mena, Elijah L., Donahue, Callie J., Vaites, Laura Pontano, Li, Jie, Rona, Gergely, O’Leary, Colin, Lignitto, Luca, Miwatani-Minter, Bearach, Paulo, Joao A., Dhabaria, Avantika, Ueberheide, Beatrix, Gygi, Steven P., Pagano, Michele, Harper, J. Wade, Davey, Robert A., and Elledge, Stephen J.

Published
2021

31. Mitochondrial inorganic polyphosphate is required to maintain proteostasis within the organelle.

Author

Da Costa, Renata T., Urquiza, Pedro, Perez, Matheus M., YunGuang Du, Mei Li Khong, Haiyan Zheng, Guitart-Mampel, Mariona, Elustondo, Pia A., Scoma, Ernest R., Hambardikar, Vedangi, Ueberheide, Beatrix, Tanner, Julian A., Cohen, Alejandro, Pavlov, Evgeny V., Haynes, Cole M., and Solesio, Maria E.

Subjects
MITOCHONDRIA, ENERGY metabolism, PROTEIN metabolism, CARRIER proteins, HOMEOSTASIS
Abstract

The existing literature points towards the presence of robust mitochondrial mechanisms aimed at mitigating protein dyshomeostasis within the organelle. However, the precise molecular composition of these mechanisms remains unclear. Our data show that inorganic polyphosphate (polyP), a polymer wellconserved throughout evolution, is a component of these mechanisms. In mammals, mitochondria exhibit a significant abundance of polyP, and both our research and that of others have already highlighted its potent regulatory effect on bioenergetics. Given the intimate connection between energy metabolism and protein homeostasis, the involvement of polyP in proteostasis has also been demonstrated in several organisms. For example, polyP is a bacterial primordial chaperone, and its role in amyloidogenesis has already been established. Here, using mammalian models, our study reveals that the depletion of mitochondrial polyP leads to increased protein aggregation within the organelle, following stress exposure. Furthermore, mitochondrial polyP is able to bind to proteins, and these proteins differ under control and stress conditions. The depletion of mitochondrial polyP significantly affects the proteome under both control and stress conditions, while also exerting regulatory control over gene expression. Our findings suggest that mitochondrial polyP is a previously unrecognized, and potent component of mitochondrial proteostasis. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Using Constellation Pharmacology to Characterize a Novel α-Conotoxin from Conus ateralbus

Author

Neves, Jorge L. B., primary, Urcino, Cristoval, additional, Chase, Kevin, additional, Dowell, Cheryl, additional, Hone, Arik J., additional, Morgenstern, David, additional, Chua, Victor M., additional, Ramiro, Iris Bea L., additional, Imperial, Julita S., additional, Leavitt, Lee S., additional, Phan, Jasmine, additional, Fisher, Fernando A., additional, Watkins, Maren, additional, Raghuraman, Shrinivasan, additional, Tun, Jortan O., additional, Ueberheide, Beatrix M., additional, McIntosh, J. Michael, additional, Vasconcelos, Vitor, additional, Olivera, Baldomero M., additional, and Gajewiak, Joanna, additional

Published
2024
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33. D-type cyclins regulate DNA mismatch repair in the G1 and S phases of the cell cycle, maintaining genome stability

Author

Rona, Gergely, primary, Miwatani-Minter, Bearach, additional, Zhang, Qingyue, additional, Goldberg, Hailey V., additional, Kerzhnerman, Marc A., additional, Howard, Jesse B., additional, Simoneschi, Daniele, additional, Lane, Ethan, additional, Hobbs, John W., additional, Sassani, Elizabeth, additional, Wang, Andrew A., additional, Keegan, Sarah, additional, Laverty, Daniel J., additional, Piett, Cortt G., additional, Pongor, Lorinc S., additional, Xu, Miranda Li, additional, Andrade, Joshua, additional, Thomas, Anish, additional, Sicinski, Piotr, additional, Askenazi, Manor, additional, Ueberheide, Beatrix, additional, Fenyö, David, additional, Nagel, Zachary D., additional, and Pagano, Michele, additional

Published
2024
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34. De Novo Sequencing and Resurrection of a Human Astrovirus-Neutralizing Antibody

Author

Bogdanoff, Walter A, Morgenstern, David, Bern, Marshall, Ueberheide, Beatrix M, Sanchez-Fauquier, Alicia, and DuBois, Rebecca M

Subjects
Biomedical and Clinical Sciences, Immunology, Biotechnology, Immunization, Infectious Diseases, Vaccine Related, Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, astrovirus, antibody, X-ray crystallography, mass spectrometry, protein sequencing, protein engineering, Medical Microbiology, Medical microbiology
Abstract

Monoclonal antibody (mAb) therapeutics targeting cancer, autoimmune diseases, inflammatory diseases, and infectious diseases are growing exponentially. Although numerous panels of mAbs targeting infectious disease agents have been developed, their progression into clinically useful mAbs is often hindered by the lack of sequence information and/or loss of hybridoma cells that produce them. Here we combine the power of crystallography and mass spectrometry to determine the amino acid sequence and glycosylation modification of the Fab fragment of a potent human astrovirus-neutralizing mAb. We used this information to engineer a recombinant antibody single-chain variable fragment that has the same specificity as the parent monoclonal antibody to bind to the astrovirus capsid protein. This antibody can now potentially be developed as a therapeutic and diagnostic agent.

Published
2016

37. Decoy exosomes provide protection against bacterial toxins

Author

Keller, Matthew D., Ching, Krystal L., Liang, Feng-Xia, Dhabaria, Avantika, Tam, Kayan, Ueberheide, Beatrix M., and Unutmaz, Derya

Subjects
Staphylococcus aureus -- Control, Host-bacteria relationships -- Analysis, Bacterial toxins -- Control -- Analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The production of pore-forming toxins that disrupt the plasma membrane of host cells is a common virulence strategy for bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA).sup.1-3. It is unclear, however, whether host species possess innate immune mechanisms that can neutralize pore-forming toxins during infection. We previously showed that the autophagy protein ATG16L1 is necessary for protection against MRSA strains encoding [alpha]-toxin.sup.4--a pore-forming toxin that binds the metalloprotease ADAM10 on the surface of a broad range of target cells and tissues.sup.2,5,6. Autophagy typically involves the targeting of cytosolic material to the lysosome for degradation. Here we demonstrate that ATG16L1 and other ATG proteins mediate protection against [alpha]-toxin through the release of ADAM10 on exosomes--extracellular vesicles of endosomal origin. Bacterial DNA and CpG DNA induce the secretion of ADAM10-bearing exosomes from human cells as well as in mice. Transferred exosomes protect host cells in vitro by serving as scavengers that can bind multiple toxins, and improve the survival of mice infected with MRSA in vivo. These findings indicate that ATG proteins mediate a previously unknown form of defence in response to infection, facilitating the release of exosomes that serve as decoys for bacterially produced toxins. In response to infection with Staphylococcus aureus in vitro and in vivo, host cells increase their secretion of exosomes containing ADAM10--vesicular structures that can provide protection by sequestering bacterial toxins., Author(s): Matthew D. Keller [sup.1] [sup.2] , Krystal L. Ching [sup.1] [sup.2] , Feng-Xia Liang [sup.3] [sup.4] , Avantika Dhabaria [sup.3] [sup.5] , Kayan Tam [sup.1] , Beatrix M. Ueberheide [...]

Published
2020
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41. The influence of APOEε4 on the pTau interactome in sporadic Alzheimer's disease.

Author

Thierry, Manon, Ponce, Jackeline, Martà-Ariza, Mitchell, Askenazi, Manor, Faustin, Arline, Leitner, Dominique, Pires, Geoffrey, Kanshin, Evgeny, Drummond, Eleanor, Ueberheide, Beatrix, and Wisniewski, Thomas

Subjects
ALZHEIMER'S disease, APOLIPOPROTEIN E4, BIOLOGICAL transport, CEREBRAL amyloid angiopathy, FRONTAL lobe, FALSE discovery rate
Abstract

APOEε4 is the major genetic risk factor for sporadic Alzheimer's disease (AD). Although APOEε4 is known to promote Aβ pathology, recent data also support an effect of APOE polymorphism on phosphorylated Tau (pTau) pathology. To elucidate these potential effects, the pTau interactome was analyzed across APOE genotypes in the frontal cortex of 10 advanced AD cases (n = 5 APOEε3/ε3 and n = 5 APOEε4/ε4), using a combination of anti-pTau pS396/pS404 (PHF1) immunoprecipitation (IP) and mass spectrometry (MS). This proteomic approach was complemented by an analysis of anti-pTau PHF1 and anti-Aβ 4G8 immunohistochemistry, performed in the frontal cortex of 21 advanced AD cases (n = 11 APOEε3/ε3 and n = 10 APOEε4/ε4). Our dataset includes 1130 and 1330 proteins enriched in IPPHF1 samples from APOEε3/ε3 and APOEε4/ε4 groups (fold change ≥ 1.50, IPPHF1vs IPIgG ctrl). We identified 80 and 68 proteins as probable pTau interactors in APOEε3/ε3 and APOEε4/ε4 groups, respectively (SAINT score ≥ 0.80; false discovery rate (FDR) ≤ 5%). A total of 47/80 proteins were identified as more likely to interact with pTau in APOEε3/ε3 vs APOEε4/ε4 cases. Functional enrichment analyses showed that they were significantly associated with the nucleoplasm compartment and involved in RNA processing. In contrast, 35/68 proteins were identified as more likely to interact with pTau in APOEε4/ε4 vs APOEε3/ε3 cases. They were significantly associated with the synaptic compartment and involved in cellular transport. A characterization of Tau pathology in the frontal cortex showed a higher density of plaque-associated neuritic crowns, made of dystrophic axons and synapses, in APOEε4 carriers. Cerebral amyloid angiopathy was more frequent and severe in APOEε4/ε4 cases. Our study supports an influence of APOE genotype on pTau-subcellular location in AD. These results suggest a facilitation of pTau progression to Aβ-affected brain regions in APOEε4 carriers, paving the way to the identification of new therapeutic targets. [ABSTRACT FROM AUTHOR]

Published
2024
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42. The pTau interactome in sporadic Alzheimer’s disease across APOE genotypes

Author

Thierry, Manon, primary, Ponce, Jackeline, additional, Ariza, Mitchell Marta, additional, Askenazi, Manor, additional, Faustin, Arline, additional, Leitner, Dominique, additional, Pires, Geoffrey, additional, Kanshin, Evgeny, additional, Drummond, Eleanor, additional, Ueberheide, Beatrix, additional, and Wisniewski, Thomas, additional

Published
2023
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44. Gene recoding by synonymous mutations creates promiscuous intragenic transcription initiation in mycobacteria

Author

Hegelmeyer, Nuri K., primary, Parkin, Lia A., additional, Previti, Mary L., additional, Andrade, Joshua, additional, Utama, Raditya, additional, Sejour, Richard J., additional, Gardin, Justin, additional, Muller, Stephanie, additional, Ketchum, Steven, additional, Yurovsky, Alisa, additional, Futcher, Bruce, additional, Goodwin, Sara, additional, Ueberheide, Beatrix, additional, and Seeliger, Jessica C., additional

Published
2023
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45. A noncanonical function of SKP1 regulates the switch between autophagy and unconventional secretion

Author

Li, Jie, primary, Krause, Gregory J., additional, Gui, Qi, additional, Kaushik, Susmita, additional, Rona, Gergely, additional, Zhang, Qingyue, additional, Liang, Feng-Xia, additional, Dhabaria, Avantika, additional, Anerillas, Carlos, additional, Martindale, Jennifer L., additional, Vasilyev, Nikita, additional, Askenazi, Manor, additional, Ueberheide, Beatrix, additional, Nudler, Evgeny, additional, Gorospe, Myriam, additional, Cuervo, Ana Maria, additional, and Pagano, Michele, additional

Published
2023
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47. Author Correction: Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance

Author

Daley, Donnele, Mani, Vishnu R., Mohan, Navyatha, Akkad, Neha, Ochi, Atsuo, Heindel, Daniel W., Lee, Ki Buom, Zambirinis, Constantinos P., Pandian, Gautam S. D. Balasubramania, Savadkar, Shivraj, Torres-Hernandez, Alejandro, Nayak, Shruti, Wang, Ding, Hundeyin, Mautin, Diskin, Brian, Aykut, Berk, Werba, Gregor, Barilla, Rocky M., Rodriguez, Robert, Chang, Steven, Gardner, Lawrence, Mahal, Lara K., Ueberheide, Beatrix, and Miller, George

Published
2021
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49. Synthesis, debugging, and effects of synthetic chromosome consolidation : synVI and beyond

Author

Mitchell, Leslie A., Wang, Ann, Stracquadanio, Giovanni, Kuang, Zheng, Wang, Xuya, Yang, Kun, Richardson, Sarah, Martin, J. Andrew, Zhao, Yu, Walker, Roy, Luo, Yisha, Dai, Hongjiu, Dong, Kang, Tang, Zuojian, Yang, Yanling, Cai, Yizhi, Heguy, Adriana, Ueberheide, Beatrix, Fenyö, David, Dai, Junbiao, Bader, Joel S., and Boeke, Jef D.

Published
2017

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