Dr. Melanie Alpaugh

Assistant Professor
Department of Molecular and Cellular Biology
Phone number: 
58059 / 58584
SSC 3463
SSC 3403-4

During my graduate studies, I developed a particular interest in neurodegenerative disorders in general and in Huntington’s disease specifically. My initial project centered around completing preclinical studies of a promising therapeutic, ganglioside GM1, in mouse models of Huntington’s disease. Throughout my post-doctoral training I maintained my focus in this area by studying the huntingtin protein itself and it’s capacity to display prion-like properties. This work eventually led to an interest in the interaction between misfolded forms of huntingtin and the blood brain barrier which is the foundation for my current research.

2010- B.Sc. Honors (Neuroscience), University of Alberta

2016- Ph.D. (Neuroscience), University of Alberta

2016-2017- Postdoctoral Fellow, University of Alberta

2018-2022- Postdoctoral fellow, Université Laval


The overarching goal in the lab is to understand the mechanisms and consequences of protein misfolding in neurodegenerative conditions. To enhance the clinical applicability of findings studies will be completed in models of multiple neurodegenerative conditions to facilitate the discovery of shared mechanisms. Furthermore, a combination of human tissue samples, human cell culture models and mouse models will be used to ensure relevance to human disease.

Theme 1. Understanding interactions between the blood-brain barrier and misfolded proteins in neurodegeneration

Protein accumulation and blood-brain barrier break down are common features of many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. In the Alpaugh lab we aim to understand if these two common disease features are related using a human 3D-cell culture model of the blood-brain barrier to evaluate barrier deficits in multiple degenerative conditions and how they interact with disease-associated misfolded proteins

Theme 2. Determining the contributions of huntingtin seeding and spreading to Huntington’s disease

Numerous studies have now demonstrated that the mutant huntingtin protein displays prion-like properties. However, no study to date has assessed the potential impact of these protein properties on disease progression. We are tackling this question using mouse models of Huntington’s disease and tissue from human patients with Huntington’s disease phenocopies.

Selected publications

  1. Alpaugh M*, Masnata M*, de Rus Jacquet A, Lepinay E, Denis HL, Saint-Pierre M, Davies P, Planel E and Cicchetti C; 2022; Passive immunization against phosphorylated tau improves features of Huntington’s disease pathology; Molecular Therapy; S1525-0016(22)00020-X. doi: 10.1016/j.ymthe.2022.01.020. Online ahead of print. *co-first authors
  2. Alpaugh M, Denis HL and Cicchetti F; 2021; Prion-like properties of the mutant huntingtin protein in living organisms: the evidence and the relevance; Molecular psychiatry; doi: 10.1038/s41380-021-01350-4. Online ahead of print.
  3. Alpaugh M^ and Cicchetti F^; 2021; Huntington’s disease: Lessons from prion disorders; Journal of Neurology; 268(9):3493-3504. doi: 10.1007/s00415-021-10418-8. 

^co-corresponding authors

  1. de Rus Jacquet A, Denis HL, Cicchetti F^ and Alpaugh M^; 2021; Current and future applications of induced pluripotent stem cell-based models to study pathological proteins in neurodegenerative disorders; Molecular Psychiatry; epub ahead of print. doi: 10.1038/s41380-020-00999-7.

^co-corresponding authors

  1. Rieux M*, Alpaugh M*, Sciacca G, Saint-Pierre M, Masnata M, Denis HL, Levesque SA, Hermann F, Bazenet C, Garneau AP, Isenring P, Truant R, Oueslati A, Gould PV, Ast A, Wanker EE, Lacroix S and Cicchetti F; 2020; Shedding a new light on Huntington's disease: how blood can both propagate and ameliorate disease pathology; Molecular Psychiatry; epub ahead of print. doi: 10.1038/s41380-020-0787-4.

*co-first authors

  1. Masnata M*, Sciacca G*, Maxan A*, Lauruol F, David L, Dénis H, Saint-Pierre M, Bousset L, Melki R, Kordower J, Alpaugh M^, Cicchetti F^; 2019; Demonstration of prion-like properties of mutant huntingtin fibrils in both in vitro and in vivo paradigms; Acta Neuropathologica; 137(6):981-1001. doi: 10.1007/s00401-019-01973-6.
  2. Alpaugh M, Galleguillos D, Forero J, Morales LC, Lackey SW, Kar P, Di Pardo A, Holt A, Kerr BJ, Todd KG, Baker GB, Fouad K and Sipione S; 2017; Disease-modifying effects of ganglioside GM1 In Huntington’s Disease models; EMBO Molecular Medicine; 9(11):1537-1557. doi: 10.15252/emmm.201707763.
  3. Di Pardo A, Maglione V, Alpaugh M, Horkey M, Atwal RS, Sassone J, Ciammola A, Steffan JS, Fouad K, Truant R and Sipione S; 2012; Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice; PNAS; 109(9); 3528-33. doi: 10.1073/pnas.1114502109.