Grants per year
Personal profile
Research Interests
We are investigating cellular self-renewal mechanisms, amyloid formation in the brain, and the relationship of these processes to neurodegeneration and aging. We primarily use human neurons made from induced pluripotent stem cells as well as in vitro protein aggregation models to delineate the pathogenic mechanisms of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Our group is largely focused on utilizing neurons from rare lysosomal diseases to study how alterations in biomolecule degradation pathways influence the accumulation and conformation of disease-linked proteins such as alpha-synuclein, abeta, and tau. Mechanistic insights gained from studies of rare lysosomal diseases are used as a way to view and elucidate the pathological mechanisms of common neurodegenerative diseases. Another major effort of the lab is to determine how amyloid formation influences cellular self-renewal mechanisms in neurons, such as lysosomal clearance of damaged macromolecules, and the effect on the aging process. We use the following techniques and model systems: - Differentiation of induced pluripotent stem cells into midbrain dopamine neurons to model both rare and common neurodegenerative diseases. - Analytic biochemical techniques, such as HPLC and size exclusion chromatography, to study protein accumulation and misfolding in neurons. - Analysis of protein and lipid degradation pathways in neurons with a focus on the autophagic-lysosomal clearance system by a variety of biochemical and cell biological techniques - Primary neuronal cultures and transgenic mice to study the effect of metabolic pathways on protein accumulation and aging. - Recombinant protein purification of disease-related proteins to study conformational changes in cell-free in vitro systems.
Training Experience
2012 | Postdoctoral Fellowship, Massachusetts General Hospital, Harvard Medical School |
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
PhD, Neuroscience, University of Pennsylvania
… → 2008
Research interests
- Aging
- Dementia
- Frontotemporal Dementia
- Lipid Disorders
- Metabolism
- Neuroscience
- Parkinson’s Disease
- Proteins / Macromolecules
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- 1 Similar Profiles
Network
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The role of a-synuclein accumulation in lysosomal hydrolase trafficking and function
National Institute of Neurological Disorders and Stroke
7/15/22 → 4/30/27
Project: Research project
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Predoctoral and Postdoctoral Training Program in Aging and Dementia
Vassar, R. J., Weintraub, S., Allada, R., Bevan, M. D., Caraveo Piso, G., Carvill, G. L., Chan, S., Contractor, A., Disterhoft, J. F., Dombeck, D. A., Dong, H., Ferreira, A. B., Flanagan, M. E., Gefen, T. D., Geula, C., Gratton, C., He, C., Kahnt, T., Kalb, R. G., Kennedy, A., Kessler, J., Kiskinis, E., Klein, W. L., Kozorovitskiy, Y., Krainc, D., Li, L., Mazzulli, J., Mesulam, M., Miller, R. J., Morimoto, R. I., Opal, P., Ozdinler, H., Paller, K., Parisiadou, L., Penzes, P., Pinto, L., Prakriya, M., Reber, P. J., Roberts, A. L., Rogalski, E., Savas, J. N., Surmeier Jr, D. J., Swanson, G. T., Voss, J. L., Zee, P. C. & Zelano, C.
5/1/22 → 4/30/27
Project: Research project
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Development of novel therapeutics for CLN7 Batten's disease
Mila's Miracle Foundation, Inc.
3/1/22 → 2/29/24
Project: Research project
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AAV9/MFSD8 gene therapy is effective in preclinical models of neuronal ceroid lipofuscinosis type 7 disease
Chen, X., Dong, T., Hu, Y., Shaffo, F. C., Belur, N. R., Mazzulli, J. R. & Gray, S. J., Mar 1 2022, In: Journal of Clinical Investigation. 132, 5, e146286.Research output: Contribution to journal › Article › peer-review
Open Access5 Scopus citations -
CLN7/MFSD8 may be an important factor for SARS-CoV-2 cell entry
Heinl, E. S., Lorenz, S., Schmidt, B., Nasser M Laqtom, N., Mazzulli, J. R., Francelle, L., Yu, T. W., Greenberg, B., Storch, S., Tegtmeier, I., Othmen, H., Maurer, K., Steinfurth, M., Witzgall, R., Milenkovic, V., Wetzel, C. H. & Reichold, M., Oct 21 2022, In: iScience. 25, 10, 105082.Research output: Contribution to journal › Article › peer-review
Open Access -
Farnesyltransferase inhibitor LNK-754 attenuates axonal dystrophy and reduces amyloid pathology in mice
Cuddy, L. K., Alia, A. O., Salvo, M. A., Chandra, S., Grammatopoulos, T. N., Justman, C. J., Lansbury, P. T., Mazzulli, J. R. & Vassar, R., Dec 2022, In: Molecular neurodegeneration. 17, 1, 54.Research output: Contribution to journal › Article › peer-review
Open Access1 Scopus citations -
Neuroinflammation in Gaucher disease, neuronal ceroid lipofuscinosis, and commonalities with Parkinson's disease
Francelle, L. & Mazzulli, J. R., Apr 1 2022, In: Brain research. 1780, 147798.Research output: Contribution to journal › Review article › peer-review
2 Scopus citations -
Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models
Prieto Huarcaya, S., Drobny, A., Marques, A. R. A., Di Spiezio, A., Dobert, J. P., Balta, D., Werner, C., Rizo, T., Gallwitz, L., Bub, S., Stojkovska, I., Belur, N. R., Fogh, J., Mazzulli, J. R., Xiang, W., Fulzele, A., Dejung, M., Sauer, M., Winner, B., Rose-John, S., & 3 others , 2022, In: Autophagy. 18, 5, p. 1127-1151 25 p.Research output: Contribution to journal › Article › peer-review
Open Access4 Scopus citations
Datasets
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Additional file 1 of Farnesyltransferase inhibitor LNK-754 attenuates axonal dystrophy and reduces amyloid pathology in mice
Cuddy, L. K. (Creator), Alia, A. O. (Creator), Salvo, M. A. (Creator), Chandra, S. (Creator), Grammatopoulos, T. N. (Creator), Justman, C. J. (Creator), Lansbury, P. T. (Creator), Mazzulli, J. (Creator) & Vassar, R. J. (Creator), figshare, 2022
DOI: 10.6084/m9.figshare.20522612.v1, https://springernature.figshare.com/articles/figure/Additional_file_1_of_Farnesyltransferase_inhibitor_LNK-754_attenuates_axonal_dystrophy_and_reduces_amyloid_pathology_in_mice/20522612/1
Dataset
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Additional file 2 of Farnesyltransferase inhibitor LNK-754 attenuates axonal dystrophy and reduces amyloid pathology in mice
Cuddy, L. K. (Creator), Alia, A. O. (Creator), Salvo, M. A. (Creator), Chandra, S. (Creator), Grammatopoulos, T. N. (Creator), Justman, C. J. (Creator), Lansbury, P. T. (Creator), Mazzulli, J. (Creator) & Vassar, R. J. (Creator), figshare, 2022
DOI: 10.6084/m9.figshare.20522615.v1, https://springernature.figshare.com/articles/figure/Additional_file_2_of_Farnesyltransferase_inhibitor_LNK-754_attenuates_axonal_dystrophy_and_reduces_amyloid_pathology_in_mice/20522615/1
Dataset
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Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models
Prieto Huarcaya, S. (Contributor), Drobny, A. (Creator), Marques, A. R. A. (Creator), Di Spiezio, A. (Creator), Dobert, J. P. (Creator), Balta, D. (Creator), Werner, C. (Creator), Rizo, T. (Creator), Gallwitz, L. (Creator), Bub, S. (Creator), Stojkovska, I. (Creator), Belur, N. R. (Creator), Fogh, J. (Creator), Mazzulli, J. (Creator), Xiang, W. (Creator), Fulzele, A. (Creator), Dejung, M. (Creator), Sauer, M. (Creator), Winner, B. (Creator), Rose-John, S. (Creator), Arnold, P. (Creator), Saftig, P. (Creator) & Zunke, F. (Creator), Taylor & Francis, 2022
DOI: 10.6084/m9.figshare.19360996.v3, https://tandf.figshare.com/articles/dataset/Recombinant_pro-CTSD_cathepsin_D_enhances_SNCA_-Synuclein_degradation_in_-Synucleinopathy_models/19360996/3
Dataset
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Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models
Marques, A. R. A. (Creator), Di Spiezio, A. (Creator), Dobert, J. P. (Creator), Balta, D. (Creator), Werner, C. (Creator), Rizo, T. (Creator), Gallwitz, L. (Creator), Bub, S. (Creator), Stojkovska, I. (Creator), Belur, N. R. (Creator), Fogh, J. (Creator), Mazzulli, J. (Creator), Xiang, W. (Creator), Fulzele, A. (Creator), Dejung, M. (Creator), Sauer, M. (Creator), Winner, B. (Creator), Rose-John, S. (Creator), Arnold, P. (Creator), Saftig, P. (Creator) & Zunke, F. (Creator), Taylor & Francis, 2022
DOI: 10.6084/m9.figshare.19360996.v2, https://tandf.figshare.com/articles/dataset/Recombinant_pro-CTSD_cathepsin_D_enhances_SNCA_-Synuclein_degradation_in_-Synucleinopathy_models/19360996/2
Dataset
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Additional file 4 of Farnesyltransferase inhibitor LNK-754 attenuates axonal dystrophy and reduces amyloid pathology in mice
Cuddy, L. K. (Creator), Alia, A. O. (Creator), Salvo, M. A. (Creator), Chandra, S. (Creator), Grammatopoulos, T. N. (Creator), Justman, C. J. (Creator), Lansbury, P. T. (Creator), Mazzulli, J. (Creator) & Vassar, R. J. (Creator), figshare, 2022
DOI: 10.6084/m9.figshare.20522621.v1, https://springernature.figshare.com/articles/figure/Additional_file_4_of_Farnesyltransferase_inhibitor_LNK-754_attenuates_axonal_dystrophy_and_reduces_amyloid_pathology_in_mice/20522621/1
Dataset