Mariana Mandi Gandelman

Mariana Mandi Gandelman, MSci, PhD

Languages spoken: English, Portuguese, Spanish

Academic Information

Departments Primary - Neurology

My research focuses on identifying cellular and molecular mechanisms that drive neurodegeneration and translating these mechanisms
into therapeutic targets. My work spans amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson’s disease
(PD), and spinocerebellar ataxias, with an emphasis on shared pathways that determine neuronal vulnerability and survival. I have
investigated mechanisms including neuron–glia signaling through the P2X7 receptor, protein aggregation and proteostasis, autophagy,
stress granules, ER stress, mitochondrial dysfunction, DNA-damage responses, and p53-mediated neuronal death.


More recently, my research has focused on mechanisms of neurodegeneration in spinocerebellar ataxias using all-human models,
including iPSC-derived neurons and cerebellar organoids, to define disease-associated molecular pathways and highly translational
therapeutic readouts. My long-term goal is to identify convergent mechanisms of neurodegeneration and leverage them to develop
targeted therapies that preserve neuronal function and survival.

https://medicine.utah.edu/neurology/research/pulst-scoles-lab

Education History

Postdoctoral Training University of Utah
 Postdoctoral Training
Doctoral Training Universidad de la Republica
 PHD
Post Graduate Training Universidad de la Republica
 MSci
Undergraduate Universidad de la Republica
 SB

Selected Publications

Journal Article

  1. Levy MA, Tian J, Gandelman M, Cheng H, Tsapekos M, Crego SR, Maddela R, Sinnott R (2023). A Multivitamin Mixture Protects against Oxidative Stress-Mediated Telomere Shortening. J Diet Suppl, 21(1), 53-70.
  2. Figueroa KP, Anderson CJ, Paul S, Dansithong W, Gandelman M, Scoles DR, Pulst SM (2022). Slc9a6 mutation causes Purkinje cell loss and ataxia in the shaker rat. Hum Mol Genet, 32(10), 1647-1659.
  3. Paul S, Dansithong W, Gandelman M, Figueroa KP, Zu T, Ranum LPW, Scoles DR, Pulst SM (2022). Staufen Impairs Autophagy in Neurodegeneration. Ann Neurol, 93(2), 398-416.
  4. Scoles DR, Gandelman M, Paul S, Dexheimer T, Dansithong W, Figueroa KP, Pflieger LT, Redlin S, Kales SC, Sun H, Maloney D, Damoiseaux R, Henderson MJ, Simeonov A, Jadhav A, Pulst SM (2022). A quantitative high-throughput screen identifies compounds that lower expression of the SCA2-and ALS-associated gene ATXN2. J Biol Chem, 298(8), 102228.
  5. Cendelin J, Cvetanovic M, Gandelman M, Hirai H, Orr HT, Pulst SM, Strupp M, Tichanek F, Tuma J, Manto M (2021). Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications. Cerebellum, 21(3), 452-481.
  6. Gandelman M, Dansithong W, Kales SC, Paul S, Maag G, Aoyama E, Zakharov A, Rai G, Dexheimer T, Whitehill BM, Sun H, Jadhav A, Simeonov A, Henderson MJ, Huynh DP, Pulst SM, Scoles DR (2021). The AKT modulator A-443654 reduces α-synuclein expression and normalizes ER stress and autophagy. J Biol Chem, 297(4), 101191.
  7. Paul S, Dansithong W, Figueroa KP, Gandelman M, Scoles DR, Pulst SM (2021). Staufen1 in Human Neurodegeneration. Ann Neurol, 89(6), 1114-1128.
  8. Gandelman M, Dansithong W, Figueroa KP, Paul S, Scoles DR, Pulst SM (2020). Staufen 1 amplifies proapoptotic activation of the unfolded protein response. Cell Death Differ, 27(10), 2942-2951.
  9. Scoles DR, Dansithong W, Pflieger LT, Paul S, Gandelman M, Figueroa KP, Rigo F, Bennett CF, Pulst SM (2020). ALS-associated genes in SCA2 mouse spinal cord transcriptomes. Hum Mol Genet, 29(10), 1658-1672.
  10. Gandelman M, Levy M, Cassina P, Barbeito L, Beckman JS (2013). P2X7 receptor-induced death of motor neurons by a peroxynitrite/FAS-dependent pathway. J Neurochem, 126(3), 382-8.
  11. Miquel E, Cassina A, Martnez-Palma L, Bolatto C, Tras E, Gandelman M, Radi R, Barbeito L, Cassina P (2012). Modulation of astrocytic mitochondrial function by dichloroacetate improves survival and motor performance in inherited amyotrophic lateral sclerosis. PLoS One, 7(4), e34776.
  12. Gandelman M, Peluffo H, Beckman JS, Cassina P, Barbeito L (2010). Extracellular ATP and the P2X7 receptor in astrocyte-mediated motor neuron death: implications for amyotrophic lateral sclerosis. J Neuroinflammation, 7, 33.
  13. Cassina P, Cassina A, Pehar M, Castellanos R, Gandelman M, de Len A, Robinson KM, Mason RP, Beckman JS, Barbeito L, Radi R (2008). Mitochondrial dysfunction in SOD1G93A-bearing astrocytes promotes motor neuron degeneration: prevention by mitochondrial-targeted antioxidants. J Neurosci, 28(16), 4115-22.
  14. Dupuis L, Pehar M, Cassina P, Rene F, Castellanos R, Rouaux C, Gandelman M, Dimou L, Schwab ME, Loeffler JP, Barbeito L, Gonzalez de Aguilar JL (2008). Nogo receptor antagonizes p75NTR-dependent motor neuron death. Proc Natl Acad Sci U S A, 105(2), 740-5.

Other

  1. Gandelman M, Dansithong W, Figueroa KP, Paul S, Scoles DR, Pulst SM (2021). Correction: Staufen 1 amplifies proapoptotic activation of the unfolded protein response. Cell Death Differ (28(12), p. 3374). England.