Rocha Laboratory

Idiopathic Parkinson’s disease is characterized by a loss of dopamine neurons in the substantia nigra. These dopamine neurons are highly vulnerable to oxidant stress, in part due to DA itself, which can auto-oxidize and lead to accumulation of highly toxic free radicals. Therefore, nigral dopamine neurons rely heavily on autophagic and endocytic pathways to maintain homeostasis. Deficits in autophagy and endolysosomal function are known to occur with age and in neurodegenerative diseases, like Parkinson’s disease. Using a variety of in vitro and in vivo approaches Dr. Rocha aims to understand how lysosomal dysfunction can impact protein aggregation and DA neuron vulnerability in Parkinson’s disease. Dr. Rocha’s uses a translational approach to identify and validate new therapeutic strategies to slow or halt any ongoing neurodegenerative processes in Parkinson’s disease. To achieve these goals, Dr. Rocha’s uses a multidisciplinary approach incorporating: genetic, molecular, and cellular-based techniques in cell lines, primary neurons, and rodents to understand 1. The mechanism(s) responsible for age-related endolysosomal dysfunction and 2. The molecular mechanisms that result in lysosomal dysfunction and contribute to neuronal dysfunction and eventual neurodegeneration in preclinical models of Parkinson’s disease and 3. Test and validate new neuroprotective strategies to treat Parkinson’s disease.

Specialized Areas of Research
Autophagy – lysosomal pathway in Neurodegeneration; Parkinson’s disease; Protein accumulation; Endosomal trafficking; mitochondrial dysfunction; oxidative stress.

Rocha EM, Smith GA, Park E, Cao H, Brown E, Beagan J, Schneider-Lynch ZE, Ahmadi D, Hallett PJ, and Isacson O. (2015) Progressive decline of glucocerebrosidase in aging and Parkinson’s disease Annals of Clinical and Translational Neurology.; 2(4): 433-8.

Rocha, EM, Smith, GA, Park E, Cao H, Graham A, Brown H, Hayes, MA, Beagan, JA, McLean JR, Izen, SC, Perez-Torres, EJ, Hallett, PJ, Isacson, O. (2015) Chronic pharmacological glucocerebrosidase inhibition induces alpha-synuclein aggregation, microglial and complement activation and synaptic protein changes in mice. Antioxidant Redox Signaling.; 20;23(6):550-64.

Rocha EM, Smith GA, Park E, Cao H, Brown E, Hayes MA, Beagan J, McLean JR, Izen SC, Perez-Torres E, Hallett PJ, and Isacson O. (2015) Glucocerebrosidase gene therapy prevents alpha-synucleinopathy of midbrain dopamine neurons. Neurobiology of Disease.; 82:495-503.

Di Maio, R., Hoffman,E.K., Rocha, E.M., Keeney, M.T., Sanders, L.H., De Miranda, B.R., Zharikov, A., Van Laar, A., McCoy, J. Stepan, A.F., Lanz, T.A., Kofler, J.K., Burton, E.A., Alessi, D.R., Hastings, T.G., Greenamyre, J.T. (2018) LRRK2 activation in idiopathic Parkinson Disease. Science Translational Medicine.; 10(451).

Rocha EM, De Miranda B, Sanders LH. (2018) Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease. Neurobiology of Disease.; 109(Pt B):249-257.

Rocha EM, De Miranda BR, Castro S, Drolet R, Hatcher NG, Yao L, Smith SM, Keeney MT, Di Maio R, Kofler J, Hastings TG, Greenamyre JT. (2020) LRRK2 inhibition prevents endolysosomal deficits seen in human Parkinson's disease. Neurobiology of Disease. Feb;134:104626. doi: 10.1016/j.nbd.2019.104626., 2020

Rocha EM, Keeney MT, Di Maio R, De Miranda BR, Greenamyre JT. LRRK2 and idiopathic Parkinson’s disease. Trends in Neuroscience. In Press.