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CHANTELLE SEPHTON

Professeure adjointe sous octroi
Faculté de médecine
Département de psychiatrie et de neurosciences


Coordonnées
Centre de recherche : Centre de recherche CERVO

Intérêts de recherche
Dr. Sephton’s research interests are focused on the mechanism of action of post-transcriptional regulation by RNA binding proteins. Several RNA binding proteins including TDP-43 and FUS are mutated in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Mutations in these proteins result in their cytoplasmic mislocalization and aggregation which are thought to contribute to neurodegeneration in these diseases. Stemming from her work with Gang Yu and the discovery of the biological function and RNA targets of TDP-43, her current work now focuses on understanding the mechanisms by which disease-associated mutations of TDP-43 and FUS influence RNA metabolism at the synapse and how this may lead to neurodegeneration.

Techniques
Transgenic mice, acute tissue slices, primary neuron cultures, immortalized cell-lines.

Projets
Effects of Amyotrophic Lateral Sclerosis (ALS)-linked FUS Mutations on Synaptic Function.

Mechanisms of Synaptic Dysfunction in Amyotrophic Lateral Sclerosis.

Régulation post-transcriptionnelles de l'ARN par l'ARN des protéines de liaison dans la sclérose latérale amyotrophique (SLA).

Principales publications
Ward ME, Taubes A, Chen R, Miller BL, Sephton CF, Gelfand JM, Minami S, Boscardin J, Martens LH, Seeley WW, Yu G, Herz J, Filiano AJ, Arrant AE, Roberson ED, Kraft TW, Farese RV Jr, Green A, Gan L. Early retinal neurodegeneration and impaired Ran-mediated nuclear import of TDP-43 in progranulin-deficient FTLD. J Exp Med. 2014; 211(10):1937-45. Full text

Sephton CF, Tang AA, Kulkarni A, West J, Brooks M, Stubblefield JJ, Liu Y, Zhang MQ, Green CB, Huber KM, Huang EJ, Herz J, Yu G. Activity-dependent FUS dysregulation disrupts synaptic homeostasis. Proc Natl Acad Sci U S A. 2014; 111(44):E4769-78. Full text

Dewey CM, Cenik B, Sephton CF, Johnson BA, Herz J, Yu G. TDP-43 aggregation in neurodegeneration: are stress granules the key?. Brain Res. 2012; Full text

Sephton CF, Cenik B, Cenik BK, Herz J, Yu G. TDP-43 in central nervous system development and function: clues to TDP-43-associated neurodegeneration. Biol Chem. 2012; 393(7):589-94. Full text

Sephton CF, Cenik C, Kucukural A, Dammer EB, Cenik B, Han Y, Dewey CM, Roth FP, Herz J, Peng J, Moore MJ, Yu G. Identification of neuronal RNA targets of TDP-43-containing ribonucleoprotein complexes. J Biol Chem. 2011; 286(2):1204-15. Full text

Équipe
Camille Latapy, research assistant