Cognitive Neuroepigenetics, Extinction, Memory, Anxiety Disorders
1. Society of Biological Psychiatry A.E. Bennett Research Award (2013)
2. University of Queensland Foundation Research Excellence Award (2011)
3. Australian Research Council (ARC) Australian Research Fellowship (2010-2014)
4. Keystone Symposia Travel Scholarship (2009)
5. American College of Neuropsychopharmacology (ACNP) Travel Award (2008)
6. Molecular and Cellular Cognition Society Europe (MCCS-Europe) Poster Award (2008)
7. Friends of the Semel Institute Travel Award (2008)
8. Michael Smith Foundation for Health Research (MSFHR) Fellowship (2008)
9. Canadian Institutes of Health Research (CIHR) Fellowship (2007)
10. Natural Sciences and Engineering Research Council of Canada (NSERC) Fellowship (2006)
11. Brain Research Institute/Semel Institute Travel Award (2006)
12. Society of Biological Psychiatry Travel Award (2006)
13. Fonds de la Recherche en Santé du Québec (FRSQ) Fellowship (2005)
14 Human Frontier Science Program (HFSP) Fellowship (2005)
15. Canadian Institutes of Health Research (CIHR) INMHA Brain Star Award (2004)
16. International Society for Developmental Psychobiology (ISDP) NIH Travel Award (2004)
17. International Society for Developmental Psychobiology (ISDP) Research Award (2003)
My work in cognitive neuroepigenetics has been driven by a strong interest in understanding and elucidating the molecular mechanisms of how environmental stimuli and experience translate into long-term memories. Epigenetics, broadly defined, refers to all genetic information not encoded in the DNA sequence, with the best-understood consequence of epigenetic modifications being the regulation of gene expression. Although gene transcription and protein synthesis is required for the formation of memory, the full repertoire of epigenetic mechanisms underpinning this crucial biological adaptation remain equivocal. Post-translational modification of histone proteins (i.e. acetylation, methylation etc.) and the covalent modification of DNA (i.e. methylation, hydroxymethylation and other recently discovered marks) can influence the function of the genome in a myriad of ways including the regulation of alternative splicing and transposable elements, the development of bivalent chromatin marks that render genes “poised” for transcriptional activity, and by directing nucleosome repositioning to “bookmark” recently activated genes. In addition, the majority of the genome is pervasively transcribed such that upwards of 90% of transcriptional activity is related to the production of various long non-coding RNAs (lncRNA), which possess no protein-coding capacity. The expansion of these transcriptionally active non-coding sequences in the mammalian genome appears to have occurred primarily in species with higher-order cognitive function and brain-enriched lncRNAs are expressed in both a spatiotemporal- and cell-type-specific manner. Furthermore, emerging evidence indicates that these enigmatic non-coding RNAs can function as decoys for transcription-related factors, as modular scaffolds, or as guides to direct chromatin-modifying complexes to their genomic sites of action. Thus, lncRNAs represent attractive candidates for achieving context- and stimulus-specific epigenetic regulation of gene expression; however, their role in cognition and memory remains unexplored.
JOURNAL PUBLICATIONS (Since 2011)
45. Fenton G.E., Halliday D.M., Mason R., Bredy T.W. and Stevenson C.W. (2016). Sex differences in learned fear expression and extinction involve altered gamma oscillations in medial prefrontal cortex. Neurobiology of Learning and Memory, pii: S1074-7427(16)30093-4.
44. Viola T.W., Wearick-Silva L.E., de Azeredo L.A., Centeno A., Murphy C., Marshall P., Li X., Singewald N., Garcia F., Bredy T.W. and Grassi-Oliveira R. (2016). Increased cocaine-induced conditioned place preference during periadolescence in maternally separated male BALB/c mice: the role of cortical BDNF, microRNA-212, and MeCP2. Psychopharmacology (in press)
43. Widagdo J., Zhao Q.Y., Kempen M.J., Chau Y.Q., Spadaro P.A., Ratnu V.S., Edson J., Anggono V. and Bredy T.W. (2016). Experience-dependent accumulation of N6-methyladenosine in the prefrontal cortex is associated with memory processes in mice. Journal of Neuroscience, 36(25), 6771-7.
42. Pang T., Short A., Fennell K., Perreau V.M., Fox A., O'Bryan M., Kim J.H., Bredy T.W., Hannan A.J. (2016). Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring. Translational Psychiatry, 6(6):e837.
41. Bjørge M.D., Hildrestrand G.A., Scheffler K., Suganthan R., Rolseth V., Kusnierczyk A., Rowe A.D., Vågbø C.B., Vetlesen S., Eide L., Slupphaug G., Nakabeppu Y., Bredy T.W., Klungland A. and Bjørås M. (2015). Synergistic actions of Ogg1 and Mutyh DNA glycosylases modulate anxiety-like behavior in mice. Cell Reports, 13(12), 2671-8.
40. Baker-Andresen D., Zhao Q.Y., Li X., Jupp B., Chesworth R., Lawrence A.J. and Bredy T.W. (2015). Persistent variations in neuron-specific DNA methylation following cocaine self-administration and protracted abstinence in mice. Neuroepigenetics, doi:10.1016/j.nepig.2015. 10.001
39. Spadaro P.A., Flavell C.R., Widagdo J., Ratnu V.S., Troup M., Ragan C., Mattick J.S. and Bredy T.W. (2015). Long noncoding RNA-directed epigenetic regulation of gene expression is associated with anxiety-like behavior in mice. Biological Psychiatry, doi.j.biopsych.2015.02.004
38. Ratnu V., Wei W. and Bredy T.W. (2014). Activation-induced cytidine deaminase regulates activity-dependent BDNF expression in post-mitotic cortical neurons. European Journal of Neuroscience, 40, 3032-9.
37. Li X., Baker-Andresen D., Zhao Q., Marshall V. and Bredy T.W. (2014). MBD ultra-sequencing: a novel method for identifying inter-individual and cell-type-specific variation in DNA methylation. Genes, Brain and Behaviour, 13, 721-31.
36. Li X., Wei W., Zhao Q., Widagdo J., Baker-Andresen D., Flavell C.R., D’Alessio A., Zhang Y. and Bredy T.W. (2014). Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Proceedings of the National Academy of Sciences, 111, 7120-5. (*Faculty of 1000 recommended*)
35. Fenton G.E., Pollard A.K., Halliday D.M., Mason R., Bredy T.W. and Stevenson C.W. (2014). Persistent prelimbic cortex activity contributes to enhanced learned fear expression in females. Learning and Memory, 21, 55-60.
34. Barry G., Briggs J.A., Vanichkina D.P., Poth E.M., Beveridge N.J., Ratnu V.S., Nayler S.P., Nones K., Hu J., Bredy T.W., Nakagawa S., Rigo F., Taft R.J., Cairns M.J., Blackshaw S., Wolvetang E.J. and Mattick J.S. (2014). The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Molecular Psychiatry, 19, 486-94.
33. Ploense K.L., Kerstetter K.A., Wade M.A., Woodward N.C., Maliniak D., Reyes M., Uchizono R.S., Bredy T.W. and Kippin T.E. (2013). Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior. Behavioural Pharmacology, 24, 164-71.
32. Baker-Andresen D., Flavell C., Li X. and Bredy T.W. (2013). Activation of BDNF signaling prevents the return of fear in female mice. Learning and Memory, 20, 237-40.
31. Wei W., Coelho C.M., Marek R., Yan S., Li X., Dudley K.J., Sah P., Kobor M.S. and Bredy T.W. (2012). p300/CBP-associated factor (PCAF) selectively regulates the extinction of conditioned fear. Journal of Neuroscience, 32, 11930-41.
30. Lin Q., Wei W., Coelho C.M., Boskovic Z., Ratnu V.S., Li X, Dudley K., Kobor M.S., Sun Y.E. and Bredy T.W. (2011). The brain-specific microRNA, miR-128b, regulates the formation of fear extinction memory. Nature Neuroscience, 14, 1115-7. (*Faculty of 1000 recommended*)
29. Marek R., Coelho C.M., Sullivan R.W., Ratnu, V., Dudley, K., Meyers D., Mukherjee C., Cole P.A., Sah P. and Bredy T.W. (2011). Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300. Journal of Neuroscience, 31, 7486-91.
REVIEWS AND BOOK CHAPTERS (Since 2011)
18. Nainar S., Marshall P.R., Tyler C.R., Spitale R.C. and Bredy T.W. (2016). Evolving insights into RNA modifications and their functional diversity in the brain, Nature Neuroscience (in press)
17. Ratnu V.S., Emami M. and Bredy T.W. (2016). Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain. Journal of Neuroscience Research (in press)
16. Marshall P. and Bredy T.W. (2016). Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory? Science of Learning (in press)
15. Marshall P. and Bredy T.W. (2016). What does the future hold for the study of nucleic acid modifications in the brain? In: DNA modifications in the brain” (Elsevier) (in press)
14. Bredy T.W. (2016). DNA modifications in the brain. Editor (Elsevier) (in press)
13. Alaghband Y., Bredy T.W. and Wood M.A. (2016). The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action. Neuroscience Letters. pii: S0304-3940(16)30022-2. doi: 10.1016/j.neulet.2016.01.023.
12. Flavell C.R., Lambert E.A., Winters B.D. and Bredy T.W. (2014). Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction. Frontiers in Behavioural Neuroscience, 7, 214.
11. Li X., Wei W., Ratnu V.S. and Bredy T.W. (2013). On the potential role of active DNA demethylation in establishing epigenetic states associated with neural plasticity and memory. Neurobiology of Learning and Memory, 105,125-32.
10. Marek R., Strobel C., Bredy T.W. and Sah P. (2013). The amygdala and medial prefrontal cortex: partners in the fear circuit. Journal of Physiology, 591, 2381-91.
9. Baker-Andresen D., Ratnu V.S. and Bredy, T.W. (2013). Dynamic DNA methylation: a prime candidate for genomic metaplasticity and behavioral adaptation. Trends in Neurosciences, 36, 3-13.
8. Spadaro P.A. and Bredy T.W. (2012). Emerging role of non-coding RNA in neural plasticity, cognitive function, and neuropsychiatric disorders. Frontiers in Genetics, 3, 132-16.
7. Bredy T.W., Lin Q., Wei W., Baker-Andresen D. and Mattick J.S. (2011). MicroRNA regulation of neural plasticity and memory. Neurobiology of Learning and Memory, 96, 89-94.
6. Dudley K., Li X., Kobor M.S., Kippin T.E. and Bredy T.W. (2011). Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders. Neuroscience and Biobehavioural Reviews, 35, 1544-51.
Molecular and Cellular Cognition Society (MCCS)
Society for Neuroscience
Society for Biological Psychiatry
Center for the Neurobiology of Learning and Memory