Mazzulli, Joe, PhD



Mazzulli, Joe, PhD


Assistant Professor


Office Phone





Ward 12-226


Areas of Research

Cell Biology, Molecular Neuroscience, Neurobiology of Disease

NU Scholar Profile

Recent Publications on PubMed

Current Research

Current Research

We are interested in determining how cell death occurs in age-related neurodegenerative disorders characterized by protein aggregation, such as Parkinson’s and Alzheimer’s disease. Our lab is focused on two related pathways that are critical for understanding the neurodegenerative process: 1) mechanisms that initiate and govern the conformational conversion of soluble proteins into insoluble amyloid fibrils; 2) the downstream neurotoxic effects of aggregated proteins with emphasis on the autophagic / lysosomal degradation system. We use analytic biochemical techniques and neurons generated from patient-derived induced pluripotent stem cells (iPSC) to study disease mechanisms of Parkinson’s disease and other related amyloidoses.

1) It is currently unknown how amyloid forms in the brain. Recent data suggests that dysfunction of the lysosomal degradation system contributes to the formation of Lewy bodies that characterize Parkinson’s disease (Mazzulli et al Cell 2011). To study the mechanism of this process, we generate midbrain dopamine neurons in vitro, from iPSC derived from patients with rare genetic forms of Parkinson’s disease or lysosomal storage diseases. These models are utilized to determine how disruptions in cellular degradation pathways, through rare disease causing genetic mutations, affect aging and amyloid formation in the brain.
2) It is currently unknown how the amyloid fibril forming process leads to cellular dysfunction. Data from our group indicates that a-synuclein disrupts the degradation capacity of cells through impeding the movement of hydrolases through the secretory pathway into the final destination of the lysosomal compartment. This pathogenic process can lead to multiple down stream effects including disrupted mitophagy and increased oxidative stress. We are using iPS midbrain models from Parkinson’s disease patients to understand the molecular detail of this process.

Training opportunities:
a. Culture and differentiate iPSC into midbrain neurons
b. Methods on the biochemical characterization of diseased neurons: measurement of protein solubility, amyloid formation, andsoluble oligomeric intermediates.
c. Assays related to function of the secretory pathway, autophagic delivery process, and lysosomal degradation.

Selected Publications

Selected Publications

1) Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons Chung CY, Khurana V, Auluck PK, Tardiff DF, Mazzulli JR, Soldner F, Baru V, Lou Y, Freyzon Y, Cho S, Mungenast AE, Muffat J, Mitalipova M, Pluth MD, Jui NT, Schul¨e B, Lippard SJ, Tsai L-H, Krainc D, Buchwald SL, Jaenisch R, Lindquist S.
Science. 2013 Jan;342(6161):983-987.doi:10.1126/science.1245296.
PMID: 24158904 ISSN: 00368075

2) Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies
Mazzulli JR, Xu Y-H, Sun Y, Knight AL, McLean PJ, Caldwell GA, Sidransky E, Grabowski GA, Krainc D.
Cell. 2011 Jul 8;146(1):37-52.doi:10.1016/j.cell.2011.06.001.
PMID: 21700325 PMCID: PMC3132082 ISSN: 0092867

3) Distinct region-specific α-synuclein oligomers in A53T transgenic mice: Implications for neurodegeneration
Tsika E, Moysidou M, Guo J, Cushman M, Gannon P, Sandaltzopoulos R, Giasson BI, Krainc D, Ischiropoulos H, Mazzulli JR.
Journal of Neuroscience. 2010 Mar 3;30(9):3409-3418.doi:10.1523/JNEUROSCI.4977-09.2010.
PMID: 20203200 PMCID: PMC2844128 ISSN: 02706474

4) Cytosolic catechols inhibit α-synuclein aggregation and facilitate the formation of intracellular soluble oligomeric intermediates
Mazzulli JR, Mishizen AJ, Giasson BI, Lynch DR, Thomas SA, Nakashima A, Nagatsu T, Ota A, Ischiropoulos H.
Journal of Neuroscience. 2006 Sep 27;26(39):10068-10078.doi:10.1523/JNEUROSCI.0896-06.2006.
PMID: 17005870 ISSN: 02706474