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Brady J. Maher
Brady J. Maher
Department of Psychiatry and Behavioral Sciences
855 N. Wolfe Street
Baltimore, MD 21205
Molecular and physiological basis of psychiatric disorders
My lab is focused on understanding fundamental mechanisms involved in brain development and brain function with an emphasis on how dysfunction in these mechanisms can result in neurodevelopmental and psychiatric disorders. By focusing on key developmental genes that are associated with psychiatric risk, my research group is both improving our primary understanding of brain development while also making significant inroads into identifying pathophysiological mechanisms underlying psychiatric disorders.
A current focus of my lab is to understand the function of Transcription Factor 4 (TCF4) gene. TCF4 is a clinically pleiotropic gene having association with schizophrenia and autism spectrum disorder (ASD). Autosomal dominant mutations in TCF4 result in Pitt Hopkins syndrome, a rare neurodevelopmental disorder with a variety of symptoms including developmental delays, intellectual disability, absent speech, and breathing abnormalities. My group has shown that TCF4 is an activity-dependent transcription factor that is a critical regulator of cortical development. We have shown that TCF4 regulates several developmental steps including cell fate specification, neuronal migration, cortical column formation, and neuronal excitability.
Recently, my group demonstrated that TCF4 directly regulates oligodendrocyte development and myelination. This work has led to the hypothesis that defects in myelination are a common pathophysiology across the autism spectrum. We are now working on genetic and pharmacological approaches to rescue myelination in PTHS models, with the ultimate goal of applying these therapeutic approaches more broadly to ASD.
Phan BN, Bohlen JF, Davis BA, Ye Z, Chen HY, Mayfield B, Sripathy SR, Cerceo Page S, Campbell MN, Smith HL, Gallop D, Kim H, Thaxton CL, Simon JM, Burke EE, Shin JH, Kennedy AJ, Sweatt JD, Philpot BD, Jaffe AE, Maher BJ. Nat Neurosci. 2020 Mar;23(3):375-385. doi: 10.1038/s41593-019-0578-x. Epub 2020 Feb 3. PMID: 32015540
Rannals MD, Hamersky GR, Page SC, Campbell MN, Briley A, Gallo RA, Phan BN, Hyde TM, Kleinman JE, Shin JH, Jaffe AE, Weinberger DR, Maher BJ. Neuron. 2016 Apr 6;90(1):43-55. doi: 10.1016/j.neuron.2016.02.021. Epub 2016 Mar 10. PMID: 26971948
Page SC, Hamersky GR, Gallo RA, Rannals MD, Calcaterra NE, Campbell MN, Mayfield B, Briley A, Phan BN, Jaffe AE, Maher BJ. Mol Psychiatry. 2018 Feb;23(2):304-315. doi: 10.1038/mp.2017.37. Epub 2017 Mar 14. PMID: 28289282
Li H, Zhu Y, Morozov YM, Chen X, Page SC, Rannals MD, Maher BJ, Rakic P. Disruption of TCF4 regulatory networks leads to abnormal cortical development and mental disabilities. Mol Psychiatry. 2019 Aug;24(8):1235-1246. doi: 10.1038/s41380-019-0353-0. Epub 2019 Jan 31. PubMed PMID: 30705426.
Li H, Zhu Y, Morozov YM, Chen X, Page SC, Rannals MD, Maher BJ, Rakic P. Mol Psychiatry. 2019 Aug;24(8):1235-1246. doi: 10.1038/s41380-019-0353-0. Epub 2019 Jan 31. PMID: 30705426
Sepp M, Vihma H, Nurm K, Urb M, Page SC, Roots K, Hark A, Maher BJ, Pruunsild P, Timmusk T. J Neurosci. 2017 Oct 25;37(43):10516-10527. doi: 10.1523/JNEUROSCI.1151-17.2017. Epub 2017 Sep 26. PMID: 28951451
Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C, Yao B, Hamersky GR, Jacob F, Zhong C, Yoon KJ, Jeang W, Lin L, Li Y, Thakor J, Berg DA, Zhang C, Kang E, Chickering M, Nauen D, Ho CY, Wen Z, Christian KM, Shi PY, Maher BJ, Wu H, Jin P, Tang H, Song H, Ming GL. Cell. 2016 May 19;165(5):1238-1254. doi: 10.1016/j.cell.2016.04.032. Epub 2016 Apr 22. PMID: 27118425