Marcelo Vargas, PhD

Research interest

The long-term goal of my research program is to develop new therapeutic strategies using mechanistic insights drawn from understanding astrocyte-motor neuron interaction in amyotrophic lateral sclerosis (ALS). While the degeneration of motor neurons is the characteristic feature of ALS, astrocytes play a key role determining motor neuron fate in the course of the disease. Astrocytes from diverse ALS models induce motor neuron death in co-culture models and several strategies aimed at reverting astrocyte-mediated toxicity increase motor neuron survival and improve motor performance in ALS mouse models. Our goal is to better understand astrocyte biology and define the therapeutic value of modulating mitochondrial function, antioxidant defenses and astrocyte-neuron metabolic coupling in the context of ALS.

Honors & Awards

2010    NIH Pathway to Independence Award (K99/R00)

2007    The Milton Safenowitz Post-Doctoral Fellowship for ALS research

2003    PhD Fellowship-United Nations Developmental Program

2000    MS Fellowship-United Nations Developmental Program

Selected Publications

• Harlan BA, Killoy KM, Pehar M, Liu L, Auwerx J, Vargas MR. Evaluation of the NAD⁺ biosynthetic pathway in ALS patients and effect of modulating NAD⁺ levels in hSOD1-linked ALS mouse models. Exp. Neurol. 2020 Jan 31;327:113219. [Epub ahead of print] PubMed PMID: 32014438.
• Harlan BA, Pehar M, Killoy KM, Vargas MR. Enhanced SIRT6 activity abrogates the neurotoxic phenotype of astrocytes expressing ALS-linked mutant SOD1. FASEB J. 2019; 33(6):7084-7091. PubMed Central PMCID: PMC6529338.
• Killoy KM, Harlan BA, Pehar M, Helke KL, Johnson JA, Vargas MR. Decreased glutathione levels cause overt motor neuron degeneration in hSOD1^WT over-expressing mice. Exp. Neurol. 2018; 302:129-135; PubMed Central PMCID: PMC5849514.
• Harlan BA, Pehar M, Sharma DR, Beeson G, Beeson CC, Vargas MR. Enhancing NAD+ Salvage Pathway Reverts the Toxicity of Primary Astrocytes Expressing Amyotrophic Lateral Sclerosis-linked Mutant Superoxide Dismutase 1 (SOD1). J Biol. Chem. 2016; 291(20):10836-46. PubMed Central PMCID: PMC4865928.
• Pehar M, Ball LE, Sharma DR, Harlan BA, Comte-Walters S, Neely BA, Vargas MR. Changes in Protein Expression and Lysine Acetylation Induced by Decreased Glutathione Levels in Astrocytes. Mol. Cell Proteomics. 2016; 15(2):493-505. PubMed Central PMCID: PMC4739669.

Complete list of publications: https://www.ncbi.nlm.nih.gov/sites/myncbi/marcelo.vargas.1/bibliography/44046903/public/?sort=date&direction=descending