Parra Rivas, Leonardo | University of Maryland School of Medicine

Academic Title:

Assistant Professor

Primary Appointment:

Neurology

Email:

lparra-rivas@som.umaryland.edu

Location:

670 W Baltimore St, Baltimore, MD 21201 HSFIII Rm 6104

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Education and Training

Pontifical Catholic University of Valparaiso, BS, Biochemistry 2006
Pontifical Catholic University of Valparaiso, MS, Biochemistry 2008
University of Utah, MS, Clinical Investigation 2018
University of Utah, PhD, Neuroscience 2018
Postdoctoral Fellow, University of California San Diego, Pathology, 2024
Project Scientist, University of California San Diego, Pathology, 2025

Biosketch

Dr. Parra-Rivas is an Assistant Professor of Neurology and a member of the University of Maryland Institute for Neuroscience Discovery (UM-MIND) at the University of Maryland School of Medicine. He is a molecular and cellular neuroscientist with a longstanding interest in the mechanisms of neurotransmission. His work spans studies of neurotransmitter transporters and dopamine homeostasis to mechanistic analyses of synaptic vesicle exocytosis, endocytosis, and recycling. Using multidisciplinary approaches in both mouse and human models, his laboratory seeks to define how synapses function under physiological conditions and how their disruption contributes to neurodegenerative disease.

Dr. Parra-Rivas was among the first to identify a previously unrecognized physiological role for serine-129 phosphorylation of α-synuclein, a modification long considered exclusively as a pathological hallmark of Parkinson’s disease. His work demonstrated that this phosphorylation is essential for normal α-synuclein synaptic function by enabling interactions with vesicle-associated proteins and regulating synaptic vesicle clustering, recycling, and neurotransmission. Ongoing studies in his laboratory focus on defining the context-dependent and pathophysiological roles of α-synuclein at synapses, with direct relevance to Parkinson’s disease and related neurodegenerative disorders.

Neurodegenerative diseases pose a growing challenge due to their progressive nature and the lack of disease-modifying therapies. Guided by fundamental insights into synaptic biology, a central goal of the Parra-Rivas laboratory is to identify early, targetable synaptic mechanisms and to leverage clinically relevant CRISPR-based technologies to halt or reverse disease progression in disorders such as Parkinson’s and Alzheimer’s disease.

Learn more about the Parra-Rivas lab and research at https://parra-rivaslab.com/

Research/Clinical Keywords

Neuronal cell biology, Synapse, Synaptic transmission, Exocytosis, Endocytosis, neurodegeneration, Synucleinopathies, Parkinson’s disease, Alzheimer’s disease, Gene therapy, CRISPRs

Highlighted Publications

Parra-Rivas LA, Sharma R, Rust TE, Bazick HO, Carlson-Stevermer J, Zylka MJ, Ogawa Y, Roy S. Protocol for CRISPR-based manipulation and visualization of endogenous α-synuclein in cultured mouse hippocampal neurons. STAR Protoc. 2025 Sep 19;6(3):103945. doi: 10.1016/j.xpro.2025.103945.

Aulston BD, Gimse K, Bazick HO, Kramar EA, Pizzo DP, Parra-Rivas LA, Sun J, Branes-Guerrero K, Checka N, Bagheri N, Satyadev N, Carlson-Stevermer J, Saito T, Saido TC, Audhya A, Wood MA, Zylka MJ, Saha K, Roy S. Long term rescue of Alzheimer's deficits in vivo by one-time gene-editing of App C-terminus. bioRxiv. 2025 Jan 7;. doi: 10.1101/2024.06.08.598099.

Stavsky A*, Parra-Rivas LA*, Tal S, Riba J, Madhivanan K, Roy S, Gitler D. Synapsin E-domain is essential for α-synuclein function. Elife. 2024 May 7;12. doi: 10.7554/eLife.89687.

Parra-Rivas LA, Madhivanan K, Aulston BD, Wang L, Prakashchand DD, Boyer NP, Saia-Cereda VM, Branes-Guerrero K, Pizzo DP, Bagchi P, Sundar VS, Tang Y, Das U, Scott DA, Rangamani P, Ogawa Y, Subhojit Roy. Serine-129 phosphorylation of α-synuclein is an activity-dependent trigger for physiologic protein-protein interactions and synaptic function. Neuron. 2023 Dec 20;111(24):4006-4023.e10. doi: 10.1016/j.neuron.2023.11.020.

Additional Publication Citations

Complete list of publications: https://www.ncbi.nlm.nih.gov/myncbi/leonardo.parra%20rivas.1/bibliography/public/

Boyer NP, Sharma R, Wiesner T, Parperis C, Delamare A, Pelletier F, Jullien N, Bhatt AM, Parra-Rivas LA, Kearney PJ, Shavarebi F, Leterrier C, Roy S. Spectrin condensates provide a nidus for assembling the axonal membrane-associated periodic skeleton. iScience. 2026 Jan 16;29(1):114454. doi: 10.1016/j.isci.2025.114454.

Parra-Rivas LA, Sharma R, Rust TE, Bazick HO, Carlson-Stevermer J, Zylka MJ, Ogawa Y, Roy S. Protocol for CRISPR-based manipulation and visualization of endogenous α-synuclein in cultured mouse hippocampal neurons. STAR Protoc. 2025 Sep 19;6(3):103945. doi: 10.1016/j.xpro.2025.103945.

Stavsky A*, Parra-Rivas LA*, Tal S, Riba J, Madhivanan K, Roy S, Gitler D. Synapsin E-domain is essential for α-synuclein function. Elife. 2024 May 7;12. doi: 10.7554/eLife.89687.

Parra-Rivas LA, Palfreyman MT, Vu TN, Jorgensen EM. Interspecies complementation identifies a pathway to assemble SNAREs. iScience. 2022 Jul 15;25(7):104506. doi: 10.1016/j.isci.2022.104506.

Ganguly A, Sharma R, Boyer NP, Wernert F, Phan S, Boassa D, Parra LA, Das U, Caillol G, Han X, Yates JR 3rd, Ellisman MH, Leterrier C, Roy S. Clathrin packets move in slow axonal transport and deliver functional payloads to synapses. Neuron. 2021 Sep 15;109(18):2884-2901.e7. doi: 10.1016/j.neuron.2021.08.016.

Schober ME, Requena DF, Maschek JA, Cox J, Parra LA, Lolofie A. Effects of controlled cortical impact and docosahexaenoic acid on rat pup fatty acid profiles. Behav Brain Res. 2020 Jan 27;378:112295. doi: 10.1016/j.bbr.2019.112295.

Parra LA. In Vivo Analysis of a Gain-of-Function Mutation Confirms Unc18/Munc18's Role in Priming. J Neurosci. 2018 Jan 31;38(5):1055-1057. doi: 10.1523/JNEUROSCI.3068-17.2017. Review.

Parra LA, Baust TB, Smith AD, Jaumotte JD, Zigmond MJ, Torres S, Leak RK, Pino JA, Torres GE. The Molecular Chaperone Hsc70 Interacts with Tyrosine Hydroxylase to Regulate Enzyme Activity and Synaptic Vesicle Localization. J Biol Chem. 2016 Aug 19;291(34):17510-22. doi: 10.1074/jbc.M116.728782.

Cartier EA, Parra LA, Baust TB, Quiroz M, Salazar G, Faundez V, Egaña L, Torres GE. A biochemical and functional protein complex involving dopamine synthesis and transport into synaptic vesicles. J Biol Chem. 2010 Jan 15;285(3):1957-66. doi: 10.1074/jbc.M109.054510.

Requena DF*, Parra LA*, Baust TB, Quiroz M, Leak RK, Garcia-Olivares J, Torres GE. The molecular chaperone Hsc70 interacts with the vesicular monoamine transporter-2. J Neurochem. 2009 Jul;110(2):581-94. doi: 10.1111/j.1471-4159.2009.06135.x.

Egaña LA, Cuevas RA, Baust TB, Parra LA, Leak RK, Hochendoner S, Peña K, Quiroz M, Hong WC, Dorostkar MM, Janz R, Sitte HH, Torres GE. Physical and functional interaction between the dopamine transporter and the synaptic vesicle protein synaptogyrin-3. J Neurosci. 2009 Apr 8;29(14):4592-604. doi: 10.1523/JNEUROSCI.4559-08.2009.

Parra LA, Baust T, El Mestikawy S, Quiroz M, Hoffman B, Haflett JM, Yao JK, Torres GE. The orphan transporter Rxt1/NTT4 (SLC6A17) functions as a synaptic vesicle amino acid transporter selective for proline, glycine, leucine, and alanine. Mol Pharmacol. 2008 Dec;74(6):1521-32. doi: 10.1124/mol.108.050005.

Research Interests

The Parra-Rivas laboratory investigates the molecular mechanisms of neuronal communication, with a particular focus on how presynaptic proteins regulate neurotransmitter release, synaptic vesicle organization, and recycling, and how disruption of these processes initiates and drives neurodegenerative disease. To address these questions, the laboratory integrates CRISPR/Cas9–based gene-editing strategies—including acute gene knockout, knock-in, and phospho-state manipulation—across mouse models, human iPSC-derived neurons, and brain organoids, combined with live-cell and super-resolution imaging of synaptic vesicle dynamics, ultrastructural analyses by electron microscopy, electrophysiology, and biochemical and proteomic approaches to directly link molecular mechanisms to synaptic function. The lab also employs in vivo AAV-based gene delivery and gene-editing approaches to interrogate synaptic mechanisms within intact neural circuits and to advance next-generation, disease-modifying neurotherapeutic strategies for Parkinson’s disease, Alzheimer’s disease, and related neurodegenerative disorders.