Leonardo Parra-Rivas – Research Investigator
Leonardo Parra-Rivas, PhD
Name of Institution:
University of California San Diego, San Diego, CA
Evaluating α-synuclein pathophysiology in human neurons
Dr. Parra received his B.S. and M.S. Degree in Biochemistry from the Catholic University of Valparaiso, Chile. He conducted research in the laboratory of Dr. Gonzalo Torres at the University of Pittsburgh, where he focused on the regulation of dopamine and the physiological role of brain specific transporters. Dr. Parra obtained his M.S. in Clinical Investigation and PhD in Neuroscience under the direction of Dr. Erik Jorgensen at the University of Utah (a laboratory of the Howard Hughes Medical Institute), where he studied the molecular basis of synaptic transmission, the crosstalk between neurons. Currently, he continues his post-doctoral training with Dr. Subhojit Roy at the University of California San Diego. In the Roy lab his research focuses on the molecular mechanisms underlying the functions of synaptic proteins in neurodegenerative disorders.
The overall goal of this project is to clarify the pathophysiologic roles of α-synuclein in human neurons.
There is significant evidence supporting the involvement of α-synuclein in Parkinson’s disease (PD). Aggregation of α-synuclein in nerve cells, or neurons, is the neuropathologic hallmark of PD. Moreover, α-synuclein mutations can be seen in familial disease, where the severity of PD seems to be dependent on how many mutated copies of α-synuclein are present. Given this, there has been a significant effort to understand the normal function of α-synuclein, but despite research spanning almost two decades, there is still no clear answer. Another major caveat to our understanding of α-synuclein function is that essentially all experiments have been done in mouse models or mouse neurons, and α-synuclein function in human neurons is therefore poorly understood. This project will agnostically evaluate α-synuclein pathophysiology in human neurons.
To evaluate α-synuclein function I will combine contemporary genome-editing technologies to deplete or activate α-synuclein, along with optical and electrophysiologic assays to study neuronal function in human iPSCs-derived neurons. In parallel, using new methods to model α-synuclein aggregation in human neurons, I will determine if the aggregates are harmful or protective to neurons.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
α-synuclein is a key protein involved in pathology of Parkinson’s disease. Understanding the normal function of α-synuclein and its role during disease progression is essential for the development of new therapies. I anticipate that my findings and the genetic tools developed in this project will contribute directly to future gene therapy treatments for Parkinson’s disease.