LiLian Yuan, Ph.D.

My laboratory is interested in understanding mechanisms of neuronal connectivity and plasticity, how these processes are modulated by environmental and genetic factors, and how they are altered in human diseases and under drug conditions.  We will continue to employ a combination of behavioral, physiological, pharmacological, and genomic approaches for the following projects. 

Discovering fast-acting antidepressants.  Depression is a prevalent, heterogeneous mood disorder, affecting ~16% of population worldwide.  Currently available antidepressant agents have significant therapeutic limitations including slow on-sets, treatment resistance, and a high incidence of relapse, highlighting the critical need to develop new therapies.   We seek to evaluate potential pharmacological interventions targeting glutamatergic transmission mechanisms, such as ketamine. The downside of ketamine treatment is its abuse potential and the dissociative and psychotomimetic side effects.  We are currently testing candidate drugs targeting NMDA receptors with the goal of discovering fast-acting and long-lasting antidepressants.

Gut microbiota in mood regulation.  Emerging evidence supports a bidirectional communication axis between the brain, the gastrointestinal tract, and the microbiota colonizing the gut (commonly referred to as the “brain-gut-microbiota axis”).  Using shotgun sequencing and metagenomic analysis, we investigate the role played by the gut microbiome in mood (dys) regulation resulted from chronic stress or the affective component of chronic pain.  Results on how gut microbiome help regulate the host stress response may shed light on potential targeted therapies at the microbiome for disease conditions.

Publications

Kennedy BC, JG Dimova,  S Dakoji, LL Yuan, P Tran, JC Gewirtz (2016).  Requirement of Novel Factor TMEM35 for Hippocampal Long-Term Potentiation and Memory.  Am. J. Phys. Under revision.

Duric V, S Clayton, ML Leong, LL Yuan (2016).  Comorbidity Factors and Brain Mechanisms Linking Chronic Stress and Systemic Illness,” Neural Plasticity, vol. 2016, Article ID 5460732. doi:10.1155/2016/5460732

Parent MA, DA Hottman, S Cheng, W Zhang, LL McMahon, LL Yuan*, L Li* (* corresponding authors) (2014). Simvastatin treatment enhances NMDAR-mediated synaptic transmission by upregulating the surface distribution of the GluN2B subunit. Cell. Mol. Neurobiol.  34(5): 693-705

Cheng S, D Cao, DA Hottman, LL Yuan, M Bergo, L Li (2013). Farnesyl transferase haplodeficiency reduces neuropathology and rescues cognitive function in a mouse model of Alzheimer’s Disease. J. Bio. Chem. 288(50): 35952-60, 2013

Pisansky MT, RJ Wickham, J Su, S Fretham, JC Gewirtz, LL Yuan, M Sun, M Georgieff (2013). Iron deficiency impairs pre-pulse inhibition of the startle reflex. Hippocampus. 23:952–962, 2013

Lockridge A, Newland B, Printen S, Romero GE, Yuan LL. Head movement: a novel serotonin-sensitive behavioral endpoint for tail suspension test analysis. Behav Brain Res 246:168-178., 2013

Lockridge A, Romero G, Harrington J, Newland B, Gong Z, Cameron A, Yuan LL . Timing-dependent reduction in ethanol sedation and drinking preference by NMDA receptor co-agonist d-serine. Alcohol 46:389-400., 2012

Meehan AL, Yang X, Yuan LL, Rothman SM. Levetiracetam has an activity-dependent effect on inhibitory transmission. Epilepsia 53:469-476., 2012

Parent M, Yuan LL. Automated detection and analysis of neuronal persistent activity. J Neurosci Methods 201:361-367., 2011

Meehan AL, Yang X, McAdams BD, Yuan L, Rothman SM. A new mechanism for antiepileptic drug action: vesicular entry may mediate the effects of levetiracetam. J Neurophysiol 106:1227-1239., 2011

Lockridge A, Yuan LL. Spatial learning deficits in mice lacking A-type K(+) channel subunits. Hippocampus 21:1152-1156., 2011

Zhao C, Wang L, Netoff T, Yuan LL. Dendritic mechanisms controlling the threshold and timing requirement of synaptic plasticity. Hippocampus 21:288-297., 2011

Kong F, J Zhu, J Wu, J Peng, Y Wang, Q Wang, S Fu, LL Yuan, T Li. dbCRID: A Database of Chromosomal Rearrangements in Human Diseases. Nucleic Acids Res 39: D895-900, 2011

Hoover BR, Reed MN, Su J, Penrod RD, Kotilinek LA, Grant MK, Pitstick R, Carlson GA, Lanier LM, Yuan LL, Ashe KH, Liao D. Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 68:1067-1081., 2010

Lockridge A, Su J, Yuan LL. Abnormal 5-HT modulation of stress behaviors in the Kv4.2 knockout mouse. Neuroscience 170:1086-1097., 2010

Parent MA, Wang L, Su J, Netoff T, Yuan LL. Identification of the hippocampal input to medial prefrontal cortex in vitro. Cereb Cortex 20:393-403., 2010

Wang L, Yuan LL. Activation of M2 muscarinic receptors leads to sustained suppression of hippocampal transmission in the medial prefrontal cortex. J Physiol 587:5139-5147., 2009

Chen X*, LL Yuan*, C Zhao, S Birnbaum, A Frick, WE Jung, TL Schwarz, JD Sweatt, D Johnston. ( * Co-first authors) Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons. J. Neurosci. 26: 12143-12151. , 2006

Lauver A, LL Yuan, A Jeromin, BM Nadin, J Rodriguez-Arellano, H Davies, M Steward, G-Y Wu, P Pfaffinger. Manipulating Kv4.2 expression identifies a specific component of hippocampal pyramidal neuron A current that depends upon Kv4.2 expression. J. Neurochem. 99: 1207-1223., 2006

Yuan LL, X Chen. Diversity of potassium channels in neuronal dendrites. Prog. Neurobiol. 8: 374-89., 2006

Yuan LL, X Chen, K Kunjil, P Pfaffinger, and D Johnston. Increase in the rate of inactivation of expressed and native A-type K+ channels by a MEK inhibitor. Am. J. Physiol. (Cell Physiol.) 290:C165-71., 2006

Varga AW*, LL Yuan*, AE Anderson, L Schrader, G-Y Wu, D. Johnston, JD Sweatt. (* Co-first authors) CaMKII modulates Kv4.2 channel expression and upregulates neuronal A-type potassium current. J. Neurosci. 24: 3643-3654. , 2004

Birnbaum S, A Varga, LL Yuan, A Anderson, D Sweatt, L Schrader. Functions and regulation of Kv4-family A-type potassium channels. Physiol. Rev. 84: 803-833., 2004

Johnston D, BR Christie, A Frick, R Gray, DA Hoffman, JC Magee, LK. Schexnayder, S Watanabe, LL Yuan. Active dendrites, K+ channels, and synaptic plasticity. Phil. Trans. R. Soc. Lond. B 358: 667-674, 2003

Jeromin A, LL Yuan, A Frick, P Pfaffinger, and D Johnston (2003). A modified Sindbis virus for long-term gene expression in neurons. J. Neurophys. 90:2741-2745, 2003

Liang Y, LL Yuan, R Gray and D Johnston. Calcium signaling at single mossy fiber presynaptic terminals in the rat hippocampus. J. Neurophys. 87: 1132-1137., 2002

Yuan LL, JP Adams, M Swank, JD Sweatt and D Johnston. Protein kinase modulation of dendritic transient K+ channels in hippocampus involves a MAPK pathway. J. Neurosci. 22: 4860-4868., 2002

Yuan LL and BS Ganetzky. Searching for molecules mediating glial-neuronal communication. Molecular Psychiatry 4: 408-409., 1999

Yuan LL and BS Ganetzky. A glial-neuronal signaling pathway revealed by mutations in a Neurexin-related protein. Science 283: 1343-1345., 1999

Yuan LL and XL Yang. Selective suppression of rod signal transmission by cobalt ions of low levels in carp retina. Science in China, Ser. C 402: 128-136. , 1997