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 |
Education/Academic qualification
PhD, University of Pennsylvania
… → 2008
Research interests
- Aging
- Dementia
- Frontotemporal Dementia
- Lipid Disorders
- Metabolism
- Neuroscience
- Parkinson’s Disease
- Proteins / Macromolecules
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Grants
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Mechanisms of gene regulation and RNA processing in synucleinopathies
National Institute of Neurological Disorders and Stroke
7/1/20 → 6/30/25
Project: Research project
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Generation and characterization of patient-derived iPSC-neurons expressing CLN7 mutations
Mila's Miracle Foundation, Inc.
6/1/19 → 5/31/21
Project: Research project
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Northwestern University Interdepartmental Neuroscience Postbaccalaureate Research Education Program
Parrish, T. B., Mesulam, M., Weintraub, S., Mussa-Ivaldi, F., Segraves, M., Ferreira, A. B., Miller, L. E., Heckman, C., Opal, P., Larson, C., Disterhoft, J. F., Siddique, T., Dewald, J. P. A., Paller, K., Redei, E. E., Wright, B. A., Solla, S. A., Woolley, C. S., Surmeier Jr, D. J., Reber, P. J., Raman, I. M., Kohtz, J., Allada, R., Kessler, J., Apkarian, A., Miller, R. J., Vassar, R. J., DeVries, S. H., Garcia-Anoveros, J., Acosta, A., Maccaferri, G., Beeman, M., Li, L., Martina, M., Hartmann, M. J. Z., Bevan, M. D., MacIver, M. A., Contractor, A., Radulovic, J., Dhar, S., Prakriya, M., Tresch, M. C., Shepherd, G. M. G., Hespos, S. J., Swanson, G. T., Awatramani, R., Bozza, T., Geula, C., Wang, L., McLean, D., Ozdinler, P. H., Gordon, K. E., Losh, M. C., Jayaraman, A., Nusslock, R., Dombeck, D. A., Sanchez, J. T., Gallio, M., Lee, S. S. M., Grafman, J. H., Kahnt, T., Krainc, D., Schwartz, G. W., Mazzulli, J., George Jr., A. L., Corcos, D. M., Kozorovitskiy, Y., Kearney, J. A., Wainwright, D. A., Savas, J. N., Kiskinis, E., Rogalski, E., Voss, J. L., Tysseling, V. M., Sanz-Clemente, A. & Schmidt, T. M.
National Institute of General Medical Sciences
5/1/17 → 4/30/22
Project: Research project
Research Output
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Dysregulation of the autophagic-lysosomal pathway in Gaucher and Parkinson's disease
Pitcairn, C., Wani, W. Y. & Mazzulli, J. R., Feb 2019, In: Neurobiology of Disease. 122, p. 72-82 11 p.Research output: Contribution to journal › Review article › peer-review
22 Scopus citations -
Increased Lysosomal Exocytosis Induced by Lysosomal Ca2+ Channel Agonists Protects Human Dopaminergic Neurons from α-Synuclein Toxicity
Tsunemi, T., Perez-Rosello, T., Ishiguro, Y., Yoroisaka, A., Jeon, S., Hamada, K., Rammonhan, M., Wong, Y. C., Xie, Z., Akamatsu, W., Mazzulli, J., Surmeier Jr, D. J., Hattori, N. & Krainc, D., Jul 17 2019, In: The Journal of neuroscience : the official journal of the Society for Neuroscience. 39, 29, p. 5760-5772 13 p.Research output: Contribution to journal › Article › peer-review
26 Scopus citations -
Modeling neuronopathic storage diseases with patient-derived culture systems
Zunke, F. & Mazzulli, J. R., Jul 2019, In: Neurobiology of Disease. 127, p. 147-162 16 p.Research output: Contribution to journal › Review article › peer-review
3 Scopus citations -
Patient-customized oligonucleotide therapy for a rare genetic disease
Kim, J., Hu, C., El Achkar, C. M., Black, L. E., Douville, J., Larson, A., Pendergast, M. K., Goldkind, S. F., Lee, E. A., Kuniholm, A., Soucy, A., Vaze, J., Belur, N. R., Fredriksen, K., Stojkovska, I., Tsytsykova, A., Armant, M., DiDonato, R. L., Choi, J., Cornelissen, L. & 28 others, , Oct 24 2019, In: New England Journal of Medicine. 381, 17, p. 1644-1652 9 p.Research output: Contribution to journal › Article › peer-review
92 Scopus citations -
Stress-Induced Cellular Clearance Is Mediated by the SNARE Protein ykt6 and Disrupted by α-Synuclein
Cuddy, L. K., Wani, W. Y., Morella, M. L., Pitcairn, C., Tsutsumi, K., Fredriksen, K., Justman, C. J., Grammatopoulos, T. N., Belur, N. R., Zunke, F., Subramanian, A., Affaneh, A., Lansbury, P. T. & Mazzulli, J. R., Dec 4 2019, In: Neuron. 104, 5, p. 869-884.e11Research output: Contribution to journal › Article › peer-review
10 Scopus citations