Xuanmao Chen

Xuanmao Chen

Associate Professor
Phone: (603) 862-4542
Office: Molecular, Cellular, & Biomedical Sciences, Rudman Hall Rm 389, Durham, NH 03824
Websites:

Our laboratory has two major research interests: hippocampal memory formation and primary cilia. “Memory is the glue that holds our mental life together” (Kandel et al., 2014). Aberrant “glue” affects our cognitive capacities and causes numerous cognitive dysfunction-related disorders, including dementia, amnesia, post-traumatic stress disorder (PTSD), intellectual disability, depression, schizophrenia, and autism spectrum disorder (ASD). Unraveling the mechanisms underlying learning and memory formation is needed not only to understand how we acquire and retain experiences and knowledge, but also to develop mechanism-based therapies to treat these disorders. Primary cilia are centriole-derived “cellular antennae” that detect many extracellular signals including hormones and morphogens and regulate a variety of physiological functions including sensation, cognition, and development. Human diseases caused by malfunctions in primary cilia encompass developmental disorders, obesity, neurodegeneration, psychiatric disorders, and cognitive impairments. To date, little is known about how neuronal primary cilia affect postnatal development, neural function in the adult brain, and memory formation.

The first goal of our research is to understand how a fraction of neurons in the cerebral cortex are recruited and interact with each other to encode and store associative memory. The second goal is to determine how ciliary signaling affects postnatal neurodevelopment and neuronal function in the adult brain, and thereby modulates memory formation. Our long-term vision is to build bridges connecting fundamental neuroscience research with translational medicine, facilitating the development of novel therapies to treat cognitive dysfunction-related disorders. Our vision also includes increasing efforts to train the next-generation of deep thinkers for science, while also supporting the growth of individuals pursuing careers in biotech and health professions.

Our passion and dedication to sciences have led us to make multiple fundamental discoveries. We have revealed that burst synchronization of primed hippocampal neurons is crucial (probably essential) for learning and forming trace fear memory (Zhou et al., FASEB J. 2000). We have developed the first method to quantitatively measure real-time hippocampal neuronal activity hierarchy. We initially reported that the non-linear NMDAR-mediated synaptic conductance controls the development and maintenance of neural activity hierarchy and loss of control in hierarchy leads to dissociation and psychosis (Zhou et al., bioRxiv, 523038v4). Guided by neuronal cilia directionality, we have discovered that principal neurons in the cerebral cortex, including the hippocampal CA1, subiculum, and neocortex, undergo a previously unnoticed, slow but substantial "reverse movement" for postnatal cell positioning and cortical lamination (Yang et al., bioRxiv, 473383v6).

Research Approaches: molecular biology, confocal molecular imaging, behavioral analysis, patch-clamp electrophysiology, EEG/EMG deep-electrode recording, in vivo deep-brain calcium imaging on freely behaving mice, pharmacological tools, viral vector delivery, and transgenic animal models

Lab Members: Qin An, Sumaya Akter, Soheila Mirhosseiniardakani, Sierra Walsh, Jenn Wang, Liyan Qiu, Kevin Jiang, Jemma Glenn Wilxon, Elliot Meine, Jacob Dumais, and Christopher Boujaoude.

Funding: Our research is supported by NIH Grants K01AG054729, P20GM113131, R15MH126317, and R15MH125305, COLE Research Awards, CoRE PRP awards, UNH Teaching Assistantships, Summer TA Fellowships and Dissertation Year Fellowships, and awards from the Hamel Center for Undergraduate Research.

Courses Taught

  • BCHM 860: Pharmacology
  • BCHM/BMCB 860/760: Pharmacology
  • BIOL 411: Honor/Intro Biol: Mol/Cellular
  • BIOL 411H: Hon/Intro Biol: Molec/Cell Lab
  • BMCB 760: Pharmacology
  • BMCB 795W: Invest in Molecular & Cell Bio
  • BMCB 799H: Honors Senior Thesis
  • BMS 799H: Senior Honors Thesis
  • INCO 590: Rsrch Exp/MCBS
  • INCO 790: Advanced Research Experience
  • MCBS 901: Intro to Research in Life Sci
  • MCBS 999: Doctoral Research
  • NSB 799H: Honors Senior Thesis

Education

  • Ph.D., Physiology, University of Tuebingen
  • M.S., Genetics, Fudan University
  • B.S., Biology, Nanchang University

Selected Publications

  • Yang, J., Qiu, L., Strobel, M., Kabel, A., Zha, X. -M., & Chen, X. (2020). Acid-Sensing Ion Channels Contribute to Type III Adenylyl Cyclase-Independent Acid Sensing of Mouse Olfactory Sensory Neurons. MOLECULAR NEUROBIOLOGY, 57(7), 3042-3056. doi:10.1007/s12035-020-01943-0

  • Sterpka, A., Yang, J., Strobel, M., Zhou, Y., Pauplis, C., & Chen, X. (2020). Diverged morphology changes of astrocytic and neuronal primary cilia under reactive insults. MOLECULAR BRAIN, 13(1). doi:10.1186/s13041-020-00571-y

  • Zhou, Y., Qiu, L., Wang, H., & Chen, X. (2020). Induction of activity synchronization among primed hippocampal neurons out of random dynamics is key for trace memory formation and retrieval. FASEB JOURNAL, 34(3), 3658-3676. doi:10.1096/fj.201902274R

  • Zhou, Y., Qiu, L., Sterpka, A., Wang, H., Chu, F., & Chen, X. (2019). Comparative Phosphoproteomic Profiling of Type III Adenylyl Cyclase Knockout and Control, Male, and Female Mice. FRONTIERS IN CELLULAR NEUROSCIENCE, 13. doi:10.3389/fncel.2019.00034

  • Chen, X., Luo, J., Leng, Y., Yang, Y., Zweifel, L. S., Palmiter, R. D., & Storm, D. R. (2016). Ablation of Type III Adenylyl Cyclase in Mice Causes Reduced Neuronal Activity, Altered Sleep Pattern, and Depression-like Phenotypes. BIOLOGICAL PSYCHIATRY, 80(11), 836-848. doi:10.1016/j.biopsych.2015.12.012

  • Challis, R. C., Tian, H., Wang, J., He, J., Jiang, J., Chen, X., . . . Ma, M. (2015). An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors. CURRENT BIOLOGY, 25(19), 2503-2512. doi:10.1016/j.cub.2015.07.065

  • Chen, X., Cao, H., Saraf, A., Zweifel, L. S., & Storm, D. R. (2015). Overexpression of the Type 1 Adenylyl Cyclase in the Forebrain Leads to Deficits of Behavioral Inhibition. JOURNAL OF NEUROSCIENCE, 35(1), 339-351. doi:10.1523/JNEUROSCI.2478-14.2015

  • Wardlaw, S. M., Phan, T. X., Saraf, A., Chen, X., & Storm, D. R. (2014). Genetic disruption of the core circadian clock impairs hippocampus-dependent memory. LEARNING & MEMORY, 21(8), 417-423. doi:10.1101/lm.035451.114

  • Xiang, Y. -Y., Chen, X., Li, J., Wang, S., Faclier, G., MacDonald, J. F., . . . Lu, W. -Y. (2013). Isoflurane Regulates Atypical Type-A gamma-Aminobutyric Acid Receptors in Alveolar Type II Epithelial Cells. ANESTHESIOLOGY, 118(5), 1065-1075. doi:10.1097/ALN.0b013e31828e180e

  • Chen, X., Xia, Z., & Storm, D. R. (2012). Stimulation of Electro-Olfactogram Responses in the Main Olfactory Epithelia by Airflow Depends on the Type 3 Adenylyl Cyclase. JOURNAL OF NEUROSCIENCE, 32(45), 15769-15778. doi:10.1523/JNEUROSCI.2180-12.2012

  • Chen, X., Whissell, P., Orser, B. A., & MacDonald, J. F. (2011). Functional Modifications of Acid-Sensing Ion Channels by Ligand-Gated Chloride Channels. PLOS ONE, 6(7). doi:10.1371/journal.pone.0021970

  • Chen, X., Qiu, L., Li, M., Duerrnagel, S., Orser, B. A., Xiong, Z. -G., & MacDonald, J. F. (2010). Diarylamidines: High potency inhibitors of acid-sensing ion channels. NEUROPHARMACOLOGY, 58(7), 1045-1053. doi:10.1016/j.neuropharm.2010.01.011

  • Chen, X., Numata, T., Li, M., Mori, Y., Orser, B. A., Jackson, M. F., . . . MacDonald, J. F. (2010). The modulation of TRPM7 currents by nafamostat mesilate depends directly upon extracellular concentrations of divalent cations. MOLECULAR BRAIN, 3. doi:10.1186/1756-6606-3-38

  • Beazely, M. A., Lim, A., Li, H., Trepanier, C., Chen, X., Sidhu, B., & MacDonald, J. F. (2009). Platelet-derived Growth Factor Selectively Inhibits NR2B-containing N-Methyl-D-aspartate Receptors in CA1 Hippocampal Neurons. JOURNAL OF BIOLOGICAL CHEMISTRY, 284(12), 8054-8063. doi:10.1074/jbc.M805384200

  • Paukert, M., Chen, X., Polleichtner, G., Schindelin, H., & Gruender, S. (2008). Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a. JOURNAL OF BIOLOGICAL CHEMISTRY, 283(1), 572-581. doi:10.1074/jbc.M706811200

  • Chen, X., Polleichtner, G., Kadurin, I., & Gruender, S. (2007). Zebrafish acid-sensing ion channel (ASIC) 4, characterization of homo- and heteromeric channels, and identification of regions important for activation by H+. JOURNAL OF BIOLOGICAL CHEMISTRY, 282(42), 30406-30413. doi:10.1074/jbc.M702229200

  • Chen, X., & Gruender, S. (2007). Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a. JOURNAL OF PHYSIOLOGY-LONDON, 579(3), 657-670. doi:10.1113/jphysiol.2006.120733

  • Chen, X., Paukert, M., Kadurin, I., Pusch, M., & Gruender, S. (2006). Strong modulation by RFamide neuropeptides of the ASIClb/3 heteromer in competition with extracellular calcium. NEUROPHARMACOLOGY, 50(8), 964-974. doi:10.1016/j.neuropharm.2006.01.007

  • Chen, X. M., Kalbacher, H., & Grunder, S. (2006). Interaction of acid-sensing ion channel (ASIC) 1 with the tarantula toxin psalmotoxin 1 is state dependent. JOURNAL OF GENERAL PHYSIOLOGY, 127(3), 267-276. doi:10.1085/jgp.200509409

  • Chen, X. M., Kalbacher, H., & Grunder, S. (2005). The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity. JOURNAL OF GENERAL PHYSIOLOGY, 126(1), 71-79. doi:10.1085/jgp.200509303

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