17 results on '"Joseph, Brian J."'
Search Results
2. Efficient generation of lower induced motor neurons by coupling Ngn2 expression with developmental cues
- Author
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Limone, Francesco, Guerra San Juan, Irune, Mitchell, Jana M., Smith, Janell L.M., Raghunathan, Kavya, Meyer, Daniel, Ghosh, Sulagna Dia, Couto, Alexander, Klim, Joseph R., Joseph, Brian J., Gold, John, Mello, Curtis J., Nemesh, James, Smith, Brittany M., Verhage, Matthijs, McCarroll, Steven A., Pietiläinen, Olli, Nehme, Ralda, and Eggan, Kevin
- Published
- 2023
- Full Text
- View/download PDF
3. Loss of mouse Stmn2 function causes motor neuropathy
- Author
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San Juan, Irune Guerra, primary, Nash, Leslie A., additional, Smith, Kevin S., additional, Leyton-Jaimes, Marcel F., additional, Qian, Menglu, additional, Klim, Joseph R., additional, Limone, Francesco, additional, Dorr, Alexander B., additional, Couto, Alexander, additional, Pintacuda, Greta, additional, Joseph, Brian J., additional, Whisenant, D. Eric, additional, Noble, Caroline, additional, Melnik, Veronika, additional, Potter, Deirdre, additional, Holmes, Amie, additional, Burberry, Aaron, additional, Verhage, Matthijs, additional, and Eggan, Kevin, additional
- Published
- 2022
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- View/download PDF
4. Erratum:Loss of mouse Stmn2 function causes motor neuropathy (Neuron (2022) 110(10) (1671–1688.e6), (S0896627322001763), (10.1016/j.neuron.2022.02.011))
- Author
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San Juan, Irune Guerra, Nash, Leslie A., Smith, Kevin S., Leyton-Jaimes, Marcel F., Qian, Menglu, Klim, Joseph R., Limone, Francesco, Dorr, Alexander B., Couto, Alexander, Pintacuda, Greta, Joseph, Brian J., Whisenant, D. Eric, Noble, Caroline, Melnik, Veronika, Potter, Deirdre, Holmes, Amie, Burberry, Aaron, Verhage, Matthijs, Eggan, Kevin, Human genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, and Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention
- Abstract
(Neuron 110, 1671–1688; May 18, 2022) It was brought to our attention that there is a clerical mistake in one of the panels of Figure 1 (Figure 1E) in our recent publication. The representative blots for the CNS Stmn2 protein levels in the F 2 generation of Stmn2 mutants included an incorrect duplicated blot for the GAPDH loading control in the brain samples. We have corrected this error and replaced the figure online with one that includes the correct blot for the GAPDH loading control for those samples. We would like to profoundly apologize to the readers for the oversight and honest mistake.[Formula
- Published
- 2022
5. Loss of mouse Stmn2 function causes motor neuropathy
- Author
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Guerra San Juan, Irune, primary, Nash, Leslie A., additional, Smith, Kevin S., additional, Leyton-Jaimes, Marcel F., additional, Qian, Menglu, additional, Klim, Joseph R., additional, Limone, Francesco, additional, Dorr, Alexander B., additional, Couto, Alexander, additional, Pintacuda, Greta, additional, Joseph, Brian J., additional, Whisenant, D. Eric, additional, Noble, Caroline, additional, Melnik, Veronika, additional, Potter, Deirdre, additional, Holmes, Amie, additional, Burberry, Aaron, additional, Verhage, Matthijs, additional, and Eggan, Kevin, additional
- Published
- 2022
- Full Text
- View/download PDF
6. Loss of mouse Stmn2 function causes motor neuropathy
- Author
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Guerra San Juan, Irune, Nash, Leslie A., Smith, Kevin S., Leyton-Jaimes, Marcel F., Qian, Menglu, Klim, Joseph R., Limone, Francesco, Dorr, Alexander B., Couto, Alexander, Pintacuda, Greta, Joseph, Brian J., Whisenant, D. Eric, Noble, Caroline, Melnik, Veronika, Potter, Deirdre, Holmes, Amie, Burberry, Aaron, Verhage, Matthijs, Eggan, Kevin, Guerra San Juan, Irune, Nash, Leslie A., Smith, Kevin S., Leyton-Jaimes, Marcel F., Qian, Menglu, Klim, Joseph R., Limone, Francesco, Dorr, Alexander B., Couto, Alexander, Pintacuda, Greta, Joseph, Brian J., Whisenant, D. Eric, Noble, Caroline, Melnik, Veronika, Potter, Deirdre, Holmes, Amie, Burberry, Aaron, Verhage, Matthijs, and Eggan, Kevin
- Abstract
Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration accompanied by aberrant accumulation and loss of function of the RNA-binding protein TDP43. Thus far, it remains unresolved to what extent TDP43 loss of function directly contributes to motor system dysfunction. Here, we employed gene editing to find whether the mouse ortholog of the TDP43-regulated gene STMN2 has an important function in maintaining the motor system. Both mosaic founders and homozygous loss-of-function Stmn2 mice exhibited neuromuscular junction denervation and fragmentation, resulting in muscle atrophy and impaired motor behavior, accompanied by an imbalance in neuronal microtubule dynamics in the spinal cord. The introduction of human STMN2 through BAC transgenesis was sufficient to rescue the motor phenotypes observed in Stmn2 mutant mice. Collectively, our results demonstrate that disrupting the ortholog of a single TDP43-regulated RNA is sufficient to cause substantial motor dysfunction, indicating that disruption of TDP43 function is likely a contributor to ALS.
- Published
- 2022
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7. Single-nucleus sequencing reveals enriched expression of genetic risk factors in Extratelencephalic Neurons sensitive to degeneration in ALS
- Author
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Limone, Francesco, primary, Mordes, Daniel A., additional, Couto, Alexander, additional, Joseph, Brian J., additional, Mitchell, Jana M., additional, Therrien, Martine, additional, Ghosh, Sulagna Dia, additional, Meyer, Daniel, additional, Zhang, Yingying, additional, Goldman, Melissa, additional, Bortolin, Laura, additional, Cobos, Inma, additional, Kadiu, Irena, additional, McCarroll, Steven A., additional, Stevens, Beth, additional, Pietiläinen, Olli, additional, Burberry, Aaron, additional, and Eggan, Kevin, additional
- Published
- 2021
- Full Text
- View/download PDF
8. Remotely Activated Protein-Producing Nanoparticles
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David H. Koch Institute for Integrative Cancer Research at MIT, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Chemical Engineering, Schroeder, Avi, Goldberg, Michael Solomon, Kastrup, Christian, Wang, Yingxia, Jiang, Shan, Joseph, Brian J., Levins, Christopher G., Kannan, Sneha T., Langer, Robert, Anderson, Daniel Griffith, David H. Koch Institute for Integrative Cancer Research at MIT, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Chemical Engineering, Schroeder, Avi, Goldberg, Michael Solomon, Kastrup, Christian, Wang, Yingxia, Jiang, Shan, Joseph, Brian J., Levins, Christopher G., Kannan, Sneha T., Langer, Robert, and Anderson, Daniel Griffith
- Abstract
The development of responsive nanomaterials, nanoscale systems that actively respond to stimuli, is one general goal of nanotechnology. Here we develop nanoparticles that can be controllably triggered to synthesize proteins. The nanoparticles consist of lipid vesicles filled with the cellular machinery responsible for transcription and translation, including amino acids, ribosomes, and DNA caged with a photolabile protecting group. These particles served as nanofactories capable of producing proteins including green fluorescent protein (GFP) and enzymatically active luciferase. In vitro and in vivo, protein synthesis was spatially and temporally controllable, and could be initiated by irradiating micrometer-scale regions on the time scale of milliseconds. The ability to control protein synthesis inside nanomaterials may enable new strategies to facilitate the study of orthogonal proteins in a confined environment and for remotely activated drug delivery., National Cancer Institute (U.S.) (MIT-Harvard Center for Cancer Nanotechnology Excellence Grant U54 CA151884), Marie D. and Pierre Casimir-Lambert Fund, National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051), National Institutes of Health (U.S.) (Grant EB000244)
- Published
- 2014
9. Remotely Activated Protein-Producing Nanoparticles
- Author
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Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Schroeder, Avi, Goldberg, Michael Solomon, Kastrup, Christian, Wang, Yingxia, Jiang, Shan, Joseph, Brian J., Levins, Christopher G., Kannan, Sneha T., Langer, Robert, Anderson, Daniel Griffith, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Schroeder, Avi, Goldberg, Michael Solomon, Kastrup, Christian, Wang, Yingxia, Jiang, Shan, Joseph, Brian J., Levins, Christopher G., Kannan, Sneha T., Langer, Robert, and Anderson, Daniel Griffith
- Abstract
The development of responsive nanomaterials, nanoscale systems that actively respond to stimuli, is one general goal of nanotechnology. Here we develop nanoparticles that can be controllably triggered to synthesize proteins. The nanoparticles consist of lipid vesicles filled with the cellular machinery responsible for transcription and translation, including amino acids, ribosomes, and DNA caged with a photolabile protecting group. These particles served as nanofactories capable of producing proteins including green fluorescent protein (GFP) and enzymatically active luciferase. In vitro and in vivo, protein synthesis was spatially and temporally controllable, and could be initiated by irradiating micrometer-scale regions on the time scale of milliseconds. The ability to control protein synthesis inside nanomaterials may enable new strategies to facilitate the study of orthogonal proteins in a confined environment and for remotely activated drug delivery., National Cancer Institute (U.S.) (MIT-Harvard Center for Cancer Nanotechnology Excellence Grant U54 CA151884), Marie D. and Pierre Casimir-Lambert Fund, National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051), National Institutes of Health (U.S.) (Grant EB000244)
- Published
- 2014
10. Lipid-Modified Aminoglycoside Derivatives for In Vivo siRNA Delivery
- Author
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Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Zhang, Yunlong, Pelet, Jeisa M., Heller, Daniel A., Chen, Delai, Gu, Zhen, Joseph, Brian J., Anderson, Daniel Griffith, Dong, Yizhou, Wallas, Jasmine, Pelet, Jeisa, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Zhang, Yunlong, Pelet, Jeisa M., Heller, Daniel A., Chen, Delai, Gu, Zhen, Joseph, Brian J., Anderson, Daniel Griffith, Dong, Yizhou, Wallas, Jasmine, and Pelet, Jeisa
- Abstract
Rationally designed siRNA delivery materials that are enabled by lipid-modified aminoglycosides are demonstrated. Leading materials identified are able to self-assemble with siRNA into well-defined nanoparticles and induce efficient gene knockdown both in vitro and in vivo. Histology studies and liver function tests reveal that no apparent toxicity is caused by these nanoparticles at doses over two orders of magnitude., Damon Runyon Cancer Research Foundation (DFS-#2050-10), Alnylam Pharmaceuticals (Firm), National Institutes of Health (U.S.) (grant EB000244), National Institutes of Health (U.S.) (grant 1-RO1-CA132091-03)
- Published
- 2014
11. Drug Delivery: Lipid-Modified Aminoglycoside Derivatives for In Vivo siRNA Delivery (Adv. Mater. 33/2013)
- Author
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Zhang, Yunlong, primary, Pelet, Jeisa M., additional, Heller, Daniel A., additional, Dong, Yizhou, additional, Chen, Delai, additional, Gu, Zhen, additional, Joseph, Brian J., additional, Wallas, Jasmine, additional, and Anderson, Daniel G., additional
- Published
- 2013
- Full Text
- View/download PDF
12. Lipid-Modified Aminoglycoside Derivatives for In Vivo siRNA Delivery
- Author
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Zhang, Yunlong, primary, Pelet, Jeisa M., additional, Heller, Daniel A., additional, Dong, Yizhou, additional, Chen, Delai, additional, Gu, Zhen, additional, Joseph, Brian J., additional, Wallas, Jasmine, additional, and Anderson, Daniel G., additional
- Published
- 2013
- Full Text
- View/download PDF
13. Remotely Activated Protein-Producing Nanoparticles
- Author
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Schroeder, Avi, primary, Goldberg, Michael S., additional, Kastrup, Christian, additional, Wang, Yingxia, additional, Jiang, Shan, additional, Joseph, Brian J., additional, Levins, Christopher G., additional, Kannan, Sneha T., additional, Langer, Robert, additional, and Anderson, Daniel G., additional
- Published
- 2012
- Full Text
- View/download PDF
14. Efficient generation of lower induced motor neurons by coupling Ngn2expression with developmental cues
- Author
-
Limone, Francesco, Guerra San Juan, Irune, Mitchell, Jana M., Smith, Janell L.M., Raghunathan, Kavya, Meyer, Daniel, Ghosh, Sulagna Dia, Couto, Alexander, Klim, Joseph R., Joseph, Brian J., Gold, John, Mello, Curtis J., Nemesh, James, Smith, Brittany M., Verhage, Matthijs, McCarroll, Steven A., Pietiläinen, Olli, Nehme, Ralda, and Eggan, Kevin
- Abstract
Human pluripotent stem cells (hPSCs) are a powerful tool for disease modeling of hard-to-access tissues (such as the brain). Current protocols either direct neuronal differentiation with small molecules or use transcription-factor-mediated programming. In this study, we couple overexpression of transcription factor Neurogenin2 (Ngn2) with small molecule patterning to differentiate hPSCs into lower induced motor neurons (liMoNes/liMNs). This approach induces canonical MN markers including MN-specific Hb9/MNX1in more than 95% of cells. liMNs resemble bona fidehPSC-derived MN, exhibit spontaneous electrical activity, express synaptic markers, and can contact muscle cells in vitro. Pooled, multiplexed single-cell RNA sequencing on 50 hPSC lines reveals reproducible populations of distinct subtypes of cervical and brachial MNs that resemble their in vivo, embryonic counterparts. Combining small molecule patterning with Ngn2overexpression facilitates high-yield, reproducible production of disease-relevant MN subtypes, which is fundamental in propelling our knowledge of MN biology and its disruption in disease.
- Published
- 2023
- Full Text
- View/download PDF
15. Lipid-Modified Aminoglycoside Derivatives for in vivo siRNA Delivery
- Author
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Daniel G. Anderson, Delai Chen, Daniel A. Heller, Zhen Gu, Jeisa M. Pelet, Brian Joseph, Yunlong Zhang, Yizhou Dong, Jasmine Wallas, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Zhang, Yunlong, Pelet, Jeisa M., Heller, Daniel A., Chen, Delai, Gu, Zhen, Joseph, Brian J., and Anderson, Daniel Griffith
- Subjects
Gene knockdown ,Materials science ,medicine.diagnostic_test ,Mechanical Engineering ,Aminoglycoside ,Gene Transfer Techniques ,Pharmacology ,Lipids ,In vitro ,Article ,Mice ,Aminoglycosides ,Mechanics of Materials ,In vivo ,Toxicity ,Drug delivery ,medicine ,Animals ,Humans ,General Materials Science ,RNA, Small Interfering ,Liver function tests ,HeLa Cells - Abstract
Rationally designed siRNA delivery materials that are enabled by lipid-modified aminoglycosides are demonstrated. Leading materials identified are able to self-assemble with siRNA into well-defined nanoparticles and induce efficient gene knockdown both in vitro and in vivo. Histology studies and liver function tests reveal that no apparent toxicity is caused by these nanoparticles at doses over two orders of magnitude., Damon Runyon Cancer Research Foundation (DFS-#2050-10), Alnylam Pharmaceuticals (Firm), National Institutes of Health (U.S.) (grant EB000244), National Institutes of Health (U.S.) (grant 1-RO1-CA132091-03)
- Published
- 2013
16. Remotely Activated Protein-Producing Nanoparticles
- Author
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Daniel G. Anderson, Shan Jiang, Christopher G. Levins, Avi Schroeder, Brian Joseph, Christian J. Kastrup, Yingxia Wang, Robert Langer, Michael S. Goldberg, Sneha T. Kannan, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Schroeder, Avi, Goldberg, Michael Solomon, Kastrup, Christian, Wang, Yingxia, Jiang, Shan, Joseph, Brian J., Levins, Christopher G., Kannan, Sneha T., Langer, Robert, and Anderson, Daniel Griffith
- Subjects
Materials science ,Protein Conformation ,Surface Properties ,Bioengineering ,Nanotechnology ,Protein Engineering ,Ribosome ,Article ,Green fluorescent protein ,Protein structure ,Materials Testing ,Protein biosynthesis ,General Materials Science ,Luciferase ,Particle Size ,chemistry.chemical_classification ,Mechanical Engineering ,Proteins ,General Chemistry ,Protein engineering ,Robotics ,Condensed Matter Physics ,Amino acid ,Nanostructures ,chemistry ,Drug delivery ,Biophysics ,Crystallization - Abstract
The development of responsive nanomaterials, nanoscale systems that actively respond to stimuli, is one general goal of nanotechnology. Here we develop nanoparticles that can be controllably triggered to synthesize proteins. The nanoparticles consist of lipid vesicles filled with the cellular machinery responsible for transcription and translation, including amino acids, ribosomes, and DNA caged with a photolabile protecting group. These particles served as nanofactories capable of producing proteins including green fluorescent protein (GFP) and enzymatically active luciferase. In vitro and in vivo, protein synthesis was spatially and temporally controllable, and could be initiated by irradiating micrometer-scale regions on the time scale of milliseconds. The ability to control protein synthesis inside nanomaterials may enable new strategies to facilitate the study of orthogonal proteins in a confined environment and for remotely activated drug delivery., National Cancer Institute (U.S.) (MIT-Harvard Center for Cancer Nanotechnology Excellence Grant U54 CA151884), Marie D. and Pierre Casimir-Lambert Fund, National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051), National Institutes of Health (U.S.) (Grant EB000244)
- Published
- 2012
17. Single-nucleus sequencing reveals enriched expression of genetic risk factors in extratelencephalic neurons sensitive to degeneration in ALS.
- Author
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Limone F, Mordes DA, Couto A, Joseph BJ, Mitchell JM, Therrien M, Ghosh SD, Meyer D, Zhang Y, Goldman M, Bortolin L, Cobos I, Stevens B, McCarroll SA, Kadiu I, Burberry A, Pietiläinen O, and Eggan K
- Subjects
- Humans, Risk Factors, Microglia metabolism, Microglia pathology, Cell Nucleus metabolism, Cell Nucleus genetics, Oligodendroglia metabolism, Oligodendroglia pathology, Male, Single-Cell Analysis, Sequence Analysis, RNA, Female, Middle Aged, Nerve Degeneration genetics, Nerve Degeneration pathology, Nerve Degeneration metabolism, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis pathology, Amyotrophic Lateral Sclerosis metabolism, Neurons metabolism, Neurons pathology
- Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive loss of motor function linked to degenerating extratelencephalic neurons/Betz cells (ETNs). The reasons why these neurons are selectively affected remain unclear. Here, to understand the unique molecular properties that may sensitize ETNs to ALS, we performed RNA sequencing of 79,169 single nuclei from cortices of patients and controls. In both patients and unaffected individuals, we found significantly higher expression of ALS risk genes in THY1
+ ETNs, regardless of diagnosis. In patients, this was accompanied by the induction of genes involved in protein homeostasis and stress responses that were significantly induced in a wide collection of ETNs. Examination of oligodendroglial and microglial nuclei revealed patient-specific downregulation of myelinating genes in oligodendrocytes and upregulation of an endolysosomal reactive state in microglia. Our findings suggest that selective vulnerability of extratelencephalic neurons is partly connected to their intrinsic molecular properties sensitizing them to genetics and mechanisms of degeneration., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
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