|Phone:||613-520-2600 x 7044|
|Office:||5313 Health Science Building|
Areas of Specialization / Field Affiliations
Molecular neuroscience, neurodevelopment, autism spectrum disorders, mood disorders, anti-depressants, neuroinflammation, behavioral neuroscience.
Eligible to supervise at the undergraduate and graduate level.
The Aguilar-Valles lab is looking for undergraduate students and graduate students at both the Master’s and Ph.D. level. For more information, please email a brief description of your interests and CV.
The Aguilar-Valles lab is interested in the molecular mechanisms that underlie psychiatric and neurodevelopmental disorders. We use a combination of biochemistry, molecular biology, neuronal culture and animal models to understand how genetic risk factors contribute to mental illness. Specific projects are the following:
- Autism spectrum disorders (ASD) are caused by impaired neurodevelopment that can lead to an imbalance in the ratio of excitatory to inhibitory (E/I) cortical neurotransmission. Several de novo mutations have been identified in genes controlling RNA processing and stability, including components of the macromolecular complex CCR4-NOT. CCR4-NOT controls gene expression at many different levels, including mRNA stability. We seek to investigate the effect of these mutations on brain development and ASD pathophysiology.
- Major depressive disorder (MDD) is one of the leading causes of disability worldwide, with a lifetime prevalence of 16.6 %. Current treatments are ineffective in about one third of patients, indicating the urgent need to better understand MDD pathophysiology and identify novel therapeutic targets. Specifically, we seek to understand:
- The role of IKK/NF-κB signaling pathway in the generation and treatment of depressive phenotypes: This signaling pathway is central for inflammatory response, which is dysregulated in MDD. We seek to understand the brain circuits and molecular mechanisms susceptible to the activation of this pathway and their contribution for the development of depressive-like behaviours and anti-depressant therapies.
- The contribution of the mTORC1 pathway in anti-depressant treatment. Several novel antidepressant treatments (i.e. NMDA receptor antagonists) have been shown to activate the mTORC1 pathway, which control a myriad of cellular functions, including mRNA translation initiation. We seek to understand how mRNA translation (a.k.a. protein synthesis) initiation underlies the antidepressant properties of NMDA antagonists.
- Aguilar-Valles A, Haji N, De Gregorio D, Matta-Camacho E, Eslamizade MJ, Popic J, Sharma V, Cao R, Rummel C, Tanti A, Wiebe S, Nunez N, Comai S, Nadon R, Luheshi G, Mechawar N, Turecki G, Lacaille JC, Gobbi G, Sonenberg N. Translational control of depression via phosphorylation of eukaryotic translation initiation factor 4E. In revision for Nature Communications.
- Gantois I*, Khoutorsky A*, Popic J*, Aguilar-Valles A, Freemantle E, Cao R, Sharma V, Nagpal A, Gamache K, Chapat C, Pooters T, Nader K, Lacaille J-C, Gkogkas G, Sonenberg N. Chronic metformin treatment corrects behavioral, morphological and synaptic symptoms in a Fragile X Syndrome mouse model. Nature Medicine. 23(6):674-677 *Equal contribution
- Aguilar-Valles A, Matta-Camacho E, Khoutorsky A, Nader K, Gkogkas C, Lacaille J-C, Sonenberg N (2015) Inhibition of group I metabotropic glutamate receptors reverses autistic-like phenotypes caused by deficiency of the translation repressor eIF4E Binding Protein 2. The Journal of Neuroscience. 35(31):11125-32
- Aguilar-Valles A, Inoue W, Rummel C, Luheshi GN (2015) Obesity, adipokines and neuroinflammation. Neuropharmacology. 96(Pt A): 124-34
- Aguilar-Valles A, Kim J, Jung S, Woodside B, Luheshi GN (2014) Role of brain transmigrating neutrophils in depression-like behavior during systemic infection. Molecular Psychiatry. 19(5): 599-606 (Featured in the cover)
- Aguilar-Valles A*, Vaissiere T*, Griggs E, Mikaelsson M, Takács IF, Young EJ, Rumbaugh G, Miller CA (2014) Regulating Methamphetamine-Associated Memory through an Epigenetic Writer and Eraser of Permissive Histone Methylation. Biological Psychiatry. 76(1): 57-65 *Equal contribution
- Aguilar-Valles A, Jung S, Poole S, Flores C, Luheshi GN (2012) Leptin and interleukin-6 alter the function of mesolimbic dopamine neurons in a rodent model of prenatal inflammation. Psychoneuroendocrinology. 37 (7): 956-69
- Aguilar-Valles A, Flores C, Luheshi GN (2010) Prenatal Inflammation-Induced Hypoferremia Alters Dopamine Function in the Adult Offspring in Rat: relevance for Schizophrenia. PLoS ONE 5(6): e10967
- Aguilar-Valles A, Poole S, Mistry Y, Williams S, Luheshi GN (2007) Attenuated fever in rats during late pregnancy is linked to suppressed IL-6 production after localised inflammation with turpentine. The Journal of Physiology-London. 583(1):391-403