Xuanmao Chen

ASSISTANT PROFESSOR
Phone: (603) 862-4542
Office: Molecular, Cellular, & Biomedical Sciences, Rudman Hall Rm 389, Durham, NH 03824
Xuanmao Chen

Our laboratory has two major research interests: hippocampus-dependent 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 many cognitive dysfunction-related disorders, including dementia, amnesia, post-traumatic stress disorder (PTSD), intellectual disability, autism spectrum disorder (ASD), and major depressive disorder (MDD). Unraveling the mechanisms underlying learning and hippocampus-dependent memory formation is needed not only to understand how we acquire and retain experiences, skills, and knowledge, but also to develop mechanism-based therapies to combat these cognitive dysfunction-related disorders.

Primary cilia are centriole-derived “cellular antennae” that function to detect numerous signals ranging from photons and odorants to neurotransmitters, hormones, and morphogens, and thus regulate a variety of physiological functions including sensation, cognition, and development. Human diseases caused by malfunctions in primary cilia include developmental disorders, polycystic kidney disease, obesity, neurodegeneration, and cognitive impairment. In the central nervous system, both neurons and astrocytes possess a single primary cilium. We have recently proposed that neuronal and astrocytic primary cilia exhibit a dichotomy, as distinguished by their morphological dynamics, signaling pathways, key molecular components (i.e., marker proteins), nanoscale structure, and functionality, as well as disease associations. In general, primary cilia in the brain are under-studied, and it remains to be elucidated how primary cilia modulate neuronal function and affect learning and declarative memory formation.

The first goal of my research is to determine how neuronal signal, particularly ciliary signaling, affects neuronal excitability and gene expression, and thereby modulates hippocampus-dependent memory formation. The second goal is to understand how neuronal and astrocytic primary cilia sense changes in the brain and modulate neural function in health and disease conditions. My long-term vision is to build bridges between fundamental research in neuroscience and translational research, facilitating the development of novel therapies to treat cognitive dysfunction-related disorders. My vision also includes increasing efforts to train the next generation of neuroscientists and bio-technologists, and foster the growth of pre-health sciences majors.

Key Words: Primary Cilia, Adenylyl Cyclases, Hippocampus-Dependent Memory Formation, Neural Synchronization, Cognitive Dysfunction-Related Disorders

Research Approaches: molecular biology, biochemical analysis, cellular imaging, behavioral analysis, patch-clamp electrophysiology, EEG/EMG recording, multi-channel unitary recording, in vivo deep-brain fiber-optic calcium imaging in freely behaving mice, optogenetics, pharmacological tools, viral vector delivery, and transgenic animal models

Lab Members: Yuxin Zhou, Matthew Strobel, Ashley Sterpka, Juan Yang, Liyan Qiu, Victoria Denovellis, Kelsey MacCallum, Kostandina (Dina) Bicja, Brendon Lewis, and Holly Farrell

Funding: Our research is funded by National Institutes of Health Grants R21MH105746, K01AG054729, and P20GM113131, R15MH126317, Cole Neuroscience and Behavioral Faculty Research Awards, a CoRE PRP award, UNH teaching assistantships and Summer TA Fellowships, and awards from the Hamel Center for Undergraduate Research.

Research Highlight: UNH Researchers Find Burst Synchronization of Memory Cells Critical For Learning and Forming Memories.
https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201902274R
https://neurosciencenews.com/memory-learning-cell-synchronization-15649/
https://directorsblog.nih.gov/2021/03/25/the-synchronicity-of-memory/ - Featured on NIH Director's Blog

"Impact, Not Impact Factor" (by Inder M. Verma)

Education

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

Courses Taught

  • BCHM 860: Pharmacology
  • BCHM 999: Doctoral Research
  • BCHM/BMCB 860/760: Pharmacology
  • BIOL 411: Intro Biol: Mol/Cellular/Hon
  • BIOL 411H: Hon/Principles of Biol I Lab
  • BMCB 760: Pharmacology
  • BMS 799H: Senior Honors Thesis
  • GEN 999: Doctoral Research
  • INCO 590: Rsrch Exp/MCBS
  • INCO 790: Rsrch Exp/MCBS
  • MCBS 901: Intro to Research in Life Sci
  • MCBS 999: Doctoral Thesis

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 J, 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.. Biol 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.. Curr Biol, 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.. J Neurosci, 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.. Learn Mem, 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 γ-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.. J Neurosci, 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), e21970. doi:10.1371/journal.pone.0021970

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.. Mol Brain, 3, 38. doi:10.1186/1756-6606-3-38

Chen, X., Qiu, L., Li, M., Dürrnagel, 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

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.. J Biol Chem, 284(12), 8054-8063. doi:10.1074/jbc.M805384200

Paukert, M., Chen, X., Polleichtner, G., Schindelin, H., & Gründer, S. (2008). Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a.. J Biol Chem, 283(1), 572-581. doi:10.1074/jbc.M706811200

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

Chen, X., & Gründer, S. (2007). Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a.. J Physiol, 579(Pt 3), 657-670. doi:10.1113/jphysiol.2006.120733

Chen, X., Paukert, M., Kadurin, I., Pusch, M., & Gründer, S. (2006). Strong modulation by RFamide neuropeptides of the ASIC1b/3 heteromer in competition with extracellular calcium.. Neuropharmacology, 50(8), 964-974. doi:10.1016/j.neuropharm.2006.01.007

Chen, X., Kalbacher, H., & Gründer, S. (2006). Interaction of acid-sensing ion channel (ASIC) 1 with the tarantula toxin psalmotoxin 1 is state dependent.. J Gen Physiol, 127(3), 267-276. doi:10.1085/jgp.200509409

Chen, X., Kalbacher, H., & Gründer, S. (2005). The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity.. J Gen Physiol, 126(1), 71-79. doi:10.1085/jgp.200509303