Faculty Profile

Dr. Bryen A. Jordan, Ph.D.

Bryen A. Jordan, Ph.D.

Associate Professor, Dominick P. Purpura Department of Neuroscience

Associate Professor, Department of Psychiatry and Behavioral Sciences

Areas of Research: Molecular mechanisms underlying Neurodevelopmental disorders. Local translation in neurons. Synapse to nucleus signaling. Long-term changes in neuronal function. NMDA receptors functions. ANKS1B haploinsufficiency syndrome.

Professional Interests

Exploring synaptic function and the role of synaptic dysfunction in brain diseases

How does experience alter neuronal connectivity, and what are the mechanisms that lead to these changes? These are essential questions in neuroscience, because long-lasting changes in the way neurons communicate underlie proper brain function. Many psychiatric and neurodegenerative disorders result from abnormal cellular pathways that affect how neurons communicate and how they adapt to incoming information. Even neurodevelopmental disorders such as autism, ADHD and communication disorders, are thought to arise from impaired neuronal communication arising early during development. 

Our lab uses cell and molecular biology, proteomics, imaging, rodent models, and human-derived and rodent primary neuronal cultures, to understand synaptic function and dysfunction in brain disorders. Through quantitative proteomic analyses of synaptic junctions, we identified a number of synaptic components that can shuttle to the neuronal nucleus in response to synaptic activity, and that this transport enables long-lasting changes in synaptic function. These include PRR7 and AIDA-1, which binds to NMDA receptors (NMDAR) and links synaptic activity to nuclear functions. We recently identified patients around the world harboring heterozygous and monogenic deletions of the ANKS1Bgene, which encodes for protein AIDA-1. Clinical analyses reveal that affected individuals present with a spectrum of neurodevelopmental phenotypes, including ASD, ADHD, and speech and motor deficits. These findings formalize a link between ANKS1Bhaploinsufficiency and a previously undefined syndrome. Because the mechanisms linking AIDA-1 to essential synaptic functions dysregulated in ANKS1Bhaploinsufficiency are unknown, elucidating AIDA-1 function represents a key opportunity to understand molecular mechanisms contributing to neurodevelopmental disorders and normal brain function.

In further proteomic analyses of synaptic dynamics,we also found that RNA binding proteins (RNABPs) shuttle back into synapses from the neuronal nucleus in response to neuronal activity. We found that one of these proteins, Sam68, regulates the synaptic and dendritic expression of beta-actin and is crucial for proper spine morphology and synaptic function. Sam68 has been recently implicated in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), which is a neurodegenerative disorder caused by mutations upstream of the FMR1 gene. More recently, we found that Sam68 regulates the transport and translation of Arc mRNA, and regulates specific forms of synaptic plasticity along the synaptodendritic axis. These findings suggest that Sam68 plays a role in the generation and refining of neuronal networks. With our methods and findings, we seek to understand how neurons enact long-term changes in function, how they regulate specific connections amongst their many thousand inputs, and how these processes contribute to brain disorders.

Selected Publications

Klein ME, Younts TJ, Freire Cobo C, Buxbaum AR, Aow J, Erdjument-Bromage H, Richard S, Malinow R, Neubert TA, Singer RH, Castillo PE, Jordan BA. Sam68 enables metabotropic glutamate receptor-dependent long-term depression in distal dendritic regions of CA1 hippocampal neuronsCell Reports. 2019 Nov 12;29(7):1789-1799.

Carbonell AU, Cho CH, Tindi JO, Counts PA, Bates JC, Erdjument-Bromage H, Cvejic S, Iaboni A, Kvint I, Rosensaft J, Banne E, Anagnostou E, Neubert TA, Scherer SW, Molholm S, Jordan BA. Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome. Nature Communications. 2019 Aug 6;10(1):3529. doi: 10.1038/s41467-019-11437-w.

Younts TJ, Monday HR, Dudok B, Klein ME, Jordan BA, Katona I, Castillo PE. Presynaptic protein synthesis is required for long-term plasticity of GABA release. Neuron. 2016 Oct 19; 92(2):479-492

Kravchick DO, Karpova A, Hrdinka M, Lopez-Rojas J, Iacobas S, Carbonell AU, Iacobas DA, Kreutz MR, Jordan BA. Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates NMDA mediated excitotoxicity. The EMBO Journal. 2016 Sep 1;35(17):1923-34

Tindi JO, Chávez AE, Cvejic S, Calvo-Ochoa E, Castillo PE, Jordan BA. ANKS1B Gene Product AIDA-1 Controls Hippocampal Synaptic Transmission by Regulating GluN2B Subunit Localization. Journal of Neuroscience. 2015 Jun 17;35 (24), 8986-8996

Kravchick DO, Jordan BA. Presynapses go nuclear! The EMBO Journal. 2015 Apr 15;34(8):984-6.

KleinME, Castillo PE, Jordan BA. Coordination between Translation and Degradation Regulates Inducibility of mGluR-LTD. Cell Reports. 2015 Mar 10;(10):1459-1466 

Klein ME, Younts TJ, Castillo PE, Jordan BA. RNA-binding protein Sam68 controls synapse number and local β-actin mRNA metabolism in dendrites. PNAS. 2013 Feb 19;110(8):3125-30

Mulholland PJ, Jordan BA, Chandler LJ. Chronic ethanol up-regulates the synaptic expression of the nuclear translational regulatory protein AIDA-1 in primary hippocampal neurons. Alcohol. 2012 Sep;46(6):569-76.

Zhang G, Neubert TA, Jordan BA.  RNA binding proteins accumulate at the postsynaptic density with synaptic activity. Journal of Neuroscience. 2012 Jan 11:32(2): 599-609.

Jacob AL, Jordan BA, Weinberg RJ. Organization of amyloid-beta protein precursor intracellular domain-associated protein-1 in the rat brain.  J Comp Neurol. 2010 Aug 15;518(16):3221-36.

Jordan BA, Kreutz MR.  Nucleocytoplasmic protein shuttling: the direct route in synapse-to-nucleus signaling. Trends in Neuroscience (TINS). 2009 Jul;32(7):392-401.

Jordan BA, Ziff EB.  To the Nucleus with Proteomics. In Regulation of Transcription by Neuronal Activity. Edited by: Dudek SM. Springer Science;November 2007.

Jordan BA, Fernholz BD, Khatri L, Ziff EB. Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons. Nature Neuroscience. 2007 Apr; 10(4):427-35.

Jordan BA, Fernholz BD, Neubert TA, Ziff EB: New Tricks for an Old Dog: Proteomics of the PSD. In The Dynamic Synapse: Molecular Methods in Ionotropic Receptor Biology. Volume 29. Edited by: Kittler JT, Moss SJ. Boca Raton: CRC/Taylor & Francis; 2006:37-55.

Jordan BA, Ziff EB. Getting to synaptic complexes through systems biology. Genome Biology, 2006 7:214. doi:10.1186/gb-2006-7-4-214.

Monea S, Jordan BA, Srivastava S, DeSouza S, and Ziff EB.  Membrane localization of membrane type 5 matrix metalloproteinase by AMPA receptor binding protein and cleavage of cadherins.  J. Neurosci. 2006 26: 2300-2312.

Jordan BA, Fernholz BD, Boussac M, Xu C, Grigorean G, Ziff EB, Neubert TA. Identification and verification of novel rodent postsynaptic density proteins. Mol Cell Proteomics. 2004 Sep; 3(9): 857-71.

Jordan BA, Gomes I, Rios CD, Filipovska J, Devi L.  Functional interactions between mu opioid and alpha 2A-adrenergic receptors.  Mol Pharm 2003; Dec; 64(6): 1317-24.

Gomes I, Filipovska J, Jordan BA, Devi LA.  Oligomerization of opioid receptors. Methods 27 (4): 358-365 Aug 2002.

Rios CD, Jordan BA, Gomes I, and Devi LA.  G-protein-coupled receptor dimerization: modulation of receptor function. Pharmacol Therapeut 92 (2-3): 71-87 Nov-Dec 2001.

Gomes I, Jordan BA, Gupta A, Rios C, Trapaidze N, Devi LA.  G protein coupled receptor dimerization: implications in modulating receptor function. Journal of Mol Med 79 (5-6): 226-242 Jun 2001.

Jordan BA, Trapaidze N, Gomes I, Nivarthi R, and Devi LA. Oligomerization of opioid receptors with beta 2-adrenergic receptors: a role in trafficking and mitogen-activated protein kinase activation. PNAS 2001;98(1): 343-348.

Gomes I, Jordan BA, Gupta A, Trapaidze N, Nagy V, and Devi LA. (2000) Heterodimerization of mu and delta opioid receptors: A role in opiate synergy. J Neurosci 20: RC110.

Jordan BA, Cvejic S, and Devi LA. (2000). Kappa opioid receptor endocytosis by dynorphin peptides. DNA Cell Biol 19, 19-27.

Jordan BA, Cvejic S, and Devi LA. (2000). Opioids and their complicated receptor complexes.  Neuropsychopharmacology 19, 19-27.

Jordan BA, and Devi LA. (1999). G-protein-coupled receptor heterodimerization modulates receptor function. Nature 399, 697-700.

Jordan B, and Devi LA. (1998). Molecular mechanisms of opioid receptor signal transduction. Br J Anaesth 81, 12-19.

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