Principal Investigator, Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of  Sciences.

The research of Dr. Yelin Chen focuses on the function of N-methyl-D-aspartate receptor (NMDAR) and how synapses are impaired in brain diseases. In graduate school, Dr. Chen was trained as a neuropharmacologist by Dr. P. Jeffrey Conn at Vanderbilt University Center for Neuroscience Drug Discovery, where he developed and characterized many allosteric modulators of metabotropic glutamate receptors. After graduation, Dr. Chen joined Dr. Morgan Sheng’s laboaratory first at Massachusetts Institute of Technology (Picower Institute for Learning and Memory) and then at Genentech Inc. (Department of Neuroscience) for postdoctoral training. In Dr. Sheng’s lab, Dr. Chen switched to work on another type of glutamate receptor, NMDAR, and identified a NMDAR downstream molecule Nr4a1 as a modulator of excitatory synapse. He also joined the efforts to develop a series of NMDAR positive allosteric modulators.

In 2015, Dr. Chen joined IRCBC to lead the Synapse and Brain Disease Group. Here, Dr. Chen continues working on the function of NMDAR, particularly its role in brain diseases. He made a ground breaking discovery that the activity of neuronal NMDAR could promote the proliferation and activation of glial cells through a Ptgs2-dependent pathway in brain development and injury. Dr. Chen is also working on the circuit function of NMDAR in psychiatric diseases, including depression and schizophrenia. For these purposes, he is developing tools to intervene the circuit function/dysfunction of NMDAR in vivo.

Meanwhile, Dr. Chen works on the molecular and cellular mechanisms underlying Alzheimer’s disease (AD), such as how the misregulation of AD-related molecules impairs synaptic functions and ultimately leads to neurodegeneration. For example, he is amongst the first group of scientists to show that the neurodegeneration-related molecule TDP-43 is essential for maintaining synapses and such an activity is impaired in the disease-associated TDP-43 mutations. This work strongly suggests that loss of TDP-43 function underlies the associated synapse degeneration and it will be important to compensate such a weakened activity in order to reverse the disease progress.

Significant Works

1. Zhou J., Geng Y., Su T., Wang Q., Ren Y., Zhao J., Fu C., Weber M., Lin H., Kaminker., Liu N., Sheng M., Chen Y. (2022) NMDA receptor-dependent Prostaglandin-Endoperoxide Synthase 2 induction in neurons promotes glial proliferation during brain development and injury. Cell Rep. 38(13):110557

 2. Ni J., Ren Y., Su T., Zhou J., Fu C., Lu Y., Li D., Zhao J., Li Y., Zhang Y., Fang Y., Liu N., Geng Y., Chen Y. (2022) Loss of TDP-43 function underlies hippocampal and cortical synaptic deficits in TDP-43 proteinopathies. Mol. Psychiatry (In press)

3. Hackos D.H., Lupardus P.J., Grand T., Chen Y., Wang T.M., Reynen P., Gustafson A., Wallweber H.J., Volgraf M., Sellers B.D., Schwarz J.B., Paoletti P., Sheng M., Zhou Q., Hanson J.E.. (2016) Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function. Neuron. 89:983-99.

4. Chen Y., Wang Y., Ertürk A., Kallop D., Jiang Z., Weimer R.M., Kaminker J., Sheng M. (2014) Activity-induced Nr4a1 regulates spine density and distribution pattern of excitatory synapses in pyramidal neurons. Neuron. 83:431-43. (Recommended by F1000)

5. Ayala, J.E. *, Chen Y.*, Banko J.L., Sheffler D., Williams R., Telk A.N., Watson      N.L., Xiang Z., Zhang Y., Jones P.J., Lindsley C.W., Olive M.F. and Conn P.J. (2009) mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning. Neuropsychopharmacology. 34:2057-71. (* contributed equally)

6. Chen Y., Goudet C., Pin J.P. and Conn P.J. (2008) CPPHA acts through a novel site as a positive allosteric modulator of group 1 metabotropic glutamate receptors.  Mol. Pharmacol. 73:909-18

7. Chen Y., Nong Y., Goudet C., Hemstapat K., de Paulis T., Pin J.P. and Conn J.P. (2007) Interaction of novel positive allosteric modulators of metabotropic glutamate receptor 5 with the negative allosteric antagonist site is required for potentiation of receptor responses. Mol. Pharmacol. 71:1389-98