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.
Altered expression of clock and clock-controlled genes in a hSOD1-linked amyotrophic lateral sclerosis mouse model Killoy KM, Pehar M, Harlan BA, Vargas MR. FASEB J. 2021 Feb;35(2):e21343. doi: 10.1096/fj.202000386RR. See full publication information |
FABP7 upregulation induces a neurotoxic phenotype in astrocytes Killoy KM, Harlan BA, Pehar M, Vargas MR. Glia. 2020 Dec;68(12):2693-2704. doi: 10.1002/glia.23879. Epub 2020 Jul 3. See full publication information |
Evaluation of the NAD(+) biosynthetic pathway in ALS patients and effect of modulating NAD(+) levels in hSOD1-linked ALS mouse models Harlan BA, Killoy KM, Pehar M, Liu L, Auwerx J, Vargas MR. Exp Neurol. 2020 May;327:113219. doi: 10.1016/j.expneurol.2020.113219. Epub 2020 Jan 31. See full publication information |
Effects of RAGE inhibition on the progression of the disease in hSOD1(G93A) ALS mice Liu L, Killoy KM, Vargas MR, Yamamoto Y, Pehar M. Pharmacol Res Perspect. 2020 Aug;8(4):e00636. doi: 10.1002/prp2.636. See full publication information |
Enhanced SIRT6 activity abrogates the neurotoxic phenotype of astrocytes expressing ALS-linked mutant SOD1 Harlan BA, Pehar M, Killoy KM, Vargas MR. FASEB J. 2019 Jun;33(6):7084-7091. doi: 10.1096/fj.201802752R. Epub 2019 Mar 6. See full publication information |
Nicotinamide Adenine Dinucleotide Metabolism and Neurodegeneration Pehar M, Harlan BA, Killoy KM, Vargas MR. Antioxid Redox Signal. 2018 Jun 20;28(18):1652-1668. doi: 10.1089/ars.2017.7145. Epub 2017 Jun 27. See full publication information |
Decreased glutathione levels cause overt motor neuron degeneration in hSOD1(WT) over-expressing mice Killoy KM, Harlan BA, Pehar M, Helke KL, Johnson JA, Vargas MR. Exp Neurol. 2018 Apr;302:129-135. doi: 10.1016/j.expneurol.2018.01.004. Epub 2018 Jan 4. See full publication information |
Redox Biology in Neurological Function, Dysfunction, and Aging Franco R, Vargas MR. Antioxid Redox Signal. 2018 Jun 20;28(18):1583-1586. doi: 10.1089/ars.2018.7509. Epub 2018 Apr 23. See full publication information |
Nitration and Glycation Turn Mature NGF into a Toxic Factor for Motor Neurons: A Role for p75(NTR) and RAGE Signaling in ALS Kim MJ, Vargas MR, Harlan BA, Killoy KM, Ball LE, Comte-Walters S, Gooz M, Yamamoto Y, Beckman JS, Barbeito L, Pehar M. Antioxid Redox Signal. 2018 Jun 20;28(18):1587-1602. doi: 10.1089/ars.2016.6966. Epub 2017 Jun 26. See full publication information |
Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral Sclerosis Pehar M, Harlan BA, Killoy KM, Vargas MR. Curr Pharm Des. 2017;23(33):5010-5021. doi: 10.2174/1381612823666170622095802. See full publication information |
Circadian Timekeeping, Oxidative Stress and Metabolism in ALS Models Sponsor: DHHS, PHS, NATIONAL INSTITUTES OF HEALTH Award: 7R21NS102599-03 PI: VARGAS, MARCELO R 2/15/2020 - 4/30/2022 |
NAD+ metabolism and signaling in ALS models Sponsor: DHHS, PHS, NATIONAL INSTITUTES OF HEALTH Award: 2R01NS089640-07 PI: VARGAS, MARCELO R 9/30/2020 - 8/31/2025 |
Role of FABP7 in ALS models Sponsor: DHHS, PHS, NATIONAL INSTITUTES OF HEALTH Award: 1R01NS122973-01 PI: VARGAS, MARCELO R 7/1/2021 - 4/30/2026 |
Lab Staff
To make a gift to a specific lab or researcher, please click the Make a Gift link
- Select ‘I’m making this gift ‘In Memory’ or ‘In Honor’ of a person or pet’ under Gift Options
- A selection will appear to the right, ‘Tell us about your tribute’ and select ‘In honor of’
- Enter name of lab or researcher in the Tributee Name field