Haining Zhong, Ph.D.

Haining Zhong, PhD

Senior Scientist, Vollum Institute

Biography

Haining Zhong earned his B.A. in Biological Science and Biotechnology, and B.Eng. in Electronics and Computer Science from Tsinghua University in Beijing, China in 1996. He received his Ph.D. in Neuroscience from the Johns Hopkins University School of Medicine in 2002. Zhong did postdoctoral training at the Cold Spring Harbor Laboratory and then at the Janelia Farm Research Campus of the Howard Hughes Medical Institute. In 2010 he was appointed as an assistant scientist at the Vollum Institute and was promoted to scientist in 2015.

Summary of current research

We study how the brain is regulated and changed to allow the animal to adapt to and excel in the ever-changing world. Our focus is on two types of regulations — neuromodulation and experience-dependent plasticity — using rodents as the experimental model. We harness the advantages of both in vitro and in vivo experiments depending on the specific question using a variety of approaches, including advanced microscopy, electrophysiology, optogenetics, mouse genetics, CRISPR-based gene editing, and computation. Because novel technology enables us to ask long standing questions in new ways, we also actively adapt and develop the relevant technologies, such as endogenous protein labeling, biosensors for subcellular signaling pathways and microscopy.

We have openings for highly motivated students and postdocs who are interested in these directions. Please contact Haining Zhong directly at zhong@ohsu.edu for more information.

Neuromodulation

Neuromodulation impinges powerful control over brain function and mediates the switch between different biological states: fight/flight, sleep/awake, attention, reward, stress, locomotion, etc. Defective neuromodulation has been linked to many neurological disorders and neurodegenerative diseases, such as schizophrenia, bipolar disorder and Parkinson’s disease.

Current projects

  • Dissect neuromodulatory function during animal behavior using advanced microscopy combined with novel genetically-encoded sensors we developed to monitor events downstream of neuromodulation
  • Expand development of microscopic techniques that allow faster imaging and which are easier to use and compatible with free-moving animal behaviors
  • Develop novel fluorescence sensors for imaging intracellular processes in response to diverse neurotransmitters

Experience-dependent plasticity

Experience-dependent plasticity of brain circuits underlies learning and memory.

Current projects

  • Generate genetically modified mice to visualize protein organization and dynamics in vivo as readout for neuronal properties, connectivity and plasticity
  • Explore how animal behaviors alter synaptic connectivity and strength

Selected publications

Ceballos CC, Ma L, Qin M, Zhong H. (2024) Widespread co-release of glutamate and GABA throughout the mouse brain. Commun Biol. 7(1):1502. doi: 10.1038/s42003-024-07198-y. PMID: 39537846.

 Xiong W, Qin M, Zhong H. (2024) PKA regulation of neuronal function requires the dissociation of catalytic subunits from regulatory subunits. Elife. 13:RP93766. doi: 10.7554/eLife.93766. PMID: 39508822.

Xiong W.H., Qin M., Zhong H. (2023) PKA regulation of neuronal function requires the dissociation of catalytic subunits from regulatory subunits. bioRxiv. doi: 10.1101/2023.09.05.556437. (Reviewed Preprint at eLife).

Alexei M Bygrave, Ayesha Sengupta, Ella P Jackert, Mehroz Ahmed, Beloved Adenuga, Erik Nelson, Hana L Goldschmidt, Richard C Johnson, Haining Zhong, Felix L Yeh, Morgan Sheng, Richard L Huganir. (2023) Btbd11 is an inhibitory interneuron specific synaptic scaffolding protein that supports excitatory synapse structure and function. Cell Reports. 42(6):112591.

Lei Ma, Julian Day-Cooney, Omar Jaidar Benavides, Michael A. Muniak, Maozhen Qin, Jun B. Ding, Tianyi Mao, and Haining Zhong. (2022) Locomotion activates PKA through dopamine and adenosine in striatal neurons. Nature. 611(7937):762-768 (2022).

Crystian I Massengill, Landon Bayless-Edwards, Cesar C Ceballos, Elizabeth R Cebul, James Cahill, Arpita Bharadwaj, Evan Wilson, Maozhen Qin, Matthew R Whorton, Isabelle Baconguis, Bing Ye, Tianyi Mao*, and Haining Zhong*. Sensitive genetically encoded sensors for population and subcellular imaging of cAMP in vivo. Nature Methods 2022 Nov;19(11):1461-1471. (2022). PMCID: PMC10171401 (*: co-senior authors)

Liang Wang, Chunling Wu, Wanling Peng, Ziliang Zhou, Jianzhi Zeng, Xuelin Li, Yini Yang, Shuguang Yu, Ye Zou, Mian Huang, Chang Liu, Yefei Chen, Yi Li, Panpan Ti, Wenfeng Liu, Yufeng Gao, Wei Zheng, Haining Zhong, Shangbang Gao, Zhonghua Lu, Pei-Gen Ren, Ho Leung Ng, Jie He, Shoudeng Chen, Min Xu, Yulong Li, and Jun Chu. (2022) A high-performance genetically encoded fluorescent indicator for in vivo cAMP imaging. Nature Communications. 13(1):5363.

Melander, J.B., Nayebi, A., Jongbloets, B.C., Fortin, D.A., Qin, M., Ganguli, S.*, Mao, T.*, and Zhong, H.* (2021) Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and parvalbumin-positive inhibitory interneurons. Cell Reports. 37(6):109972. (*: co-senior authors)

Zhong, H.*, Ceballos, C.C., Massengill, C.I., Muniak, M.A., Ma, L., Qin, M., Petrie, S.K., and Mao, T.  (2021) High-fidelity, efficient, and reversible labeling of endogenous proteins using CRISPR-based designer exon insertion. eLife . 10:e64911. (*: senior author)

Xiong, W.-H., Qin, M., and Zhong, H. (2021) Myristoylation alone is sufficient for PKA catalytic subunits to associate with the plasma membrane to regulate neuronal functions. PNAS. 118(15): e2021658118.

Hao Jiang, Thomas J. Esparza, Terrance T. Kummer, Haining Zhong, Jens Rettig, and David L. Brody. (2020) Live Neuron High-Content Screening Reveals Synaptotoxic Activity in Alzheimer Mouse Model Homogenates. Scientific Reports. 10(1):3412.

Haruhisa Okawa, Wan-Qing Yu, Ulf Matti, Karin Schwarz, Benjamin Odermatt, Haining Zhong, Yoshihiko Tsukamoto, Leon Lagnado, Fred Rieke, Frank Schmitz and Rachel O.L. Wong. (2019) Dynamic assembly of ribbon synapses and circuit maintenance in a vertebrate sensory system. Nature Communications 10(1):2167.

Xiong W.H., Qin M., Zhong H. (2023) PKA regulation of neuronal function requires the dissociation of catalytic subunits from regulatory subunits. bioRxiv doi: 10.1101/2023.09.05.556437. (Reviewed Preprint at eLife).

Lei Ma, Julian Day-Cooney, Omar Jaidar Benavides, Michael A. Muniak, Maozhen Qin, Jun B. Ding, Tianyi Mao, and Haining Zhong. (2022) Locomotion activates PKA through dopamine and adenosine in striatal neurons. Nature. 611(7937):762-768.

Crystian I Massengill, Landon Bayless-Edwards, Cesar C Ceballos, Elizabeth R Cebul, James Cahill, Arpita Bharadwaj, Evan Wilson, Maozhen Qin, Matthew R Whorton, Isabelle Baconguis, Bing Ye, Tianyi Mao*, and Haining Zhong*. (2022) Sensitive genetically encoded sensors for population and subcellular imaging of cAMP in vivo. Nature Methods. 19(11):1461-1471. (*: co-senior authors)

Melander, J.B., Nayebi, A., Jongbloets, B.C., Fortin, D.A., Qin, M., Ganguli, S.*, Mao, T.*, and Zhong, H.* (2021) Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and parvalbumin-positive inhibitory interneurons. Cell Reports. 37(6):109972. (*: co-senior authors)

Zhong, H.*, Ceballos, C.C., Massengill, C.I., Muniak, M.A., Ma, L., Qin, M., Petrie, S.K., and Mao, T. (2021) High-fidelity, efficient, and reversible labeling of endogenous proteins using CRISPR-based designer exon insertion. eLife. 10:e64911. (*: senior author)

Xiong, W.-H., Qin, M., and Zhong, H. (2021) Myristoylation alone is sufficient for PKA catalytic subunits to associate with the plasma membrane to regulate neuronal functions. PNAS. 118(15): e2021658118.

Ma L, Jongbloets BC, Xiong WH, Melander JB, Qin M, Lameyer TJ, Harrison MF, Zemelman BV, Mao T*, Zhong H*. (2018) A Highly Sensitive A-Kinase Activity Reporter for Imaging Neuromodulatory Events in Awake Mice. Neuron. 99(4):665-679. (Featured in a Video Abstract of Neuron). (*: co-senior authors)

Tillo, S.E., Xiong, W.-H., Takahashi, M., Miao, S., Andrade, A.L., Fortin, D.A., Yang, G., Qin, M., Smoody, B.F., Stork, P.J.S. & Zhong, H. (2017) Liberated PKA Catalytic Subunits Associate with the Membrane via Myristoylation to Preferentially Phosphorylate Membrane Substrates. Cell Reports. 19(3):617-629. doi: 10.1016/j.celrep.2017.03.070.

Fortin, D.A., Tillo, S.E., Yang, G., Rah, J.-C., Melander, J.B., Bai, S., Soler-Cedeño, O., Qin, M., Zemelman, B.V., Guo, C., Mao, T.* & Zhong, H.* (2014) Live Imaging of Endogenous PSD-95 Using ENABLED: A Conditional Strategy to Fluorescently Label Endogenous Proteins. Journal of Neuroscience. 34(50):16698-712. (*: co-senior authors. Selected as OHSU School of Medicine Paper of the Month)

Hunnicutt, B.J., Long, B.R., Kusefoglu, D., Gertz, K.J., Zhong, H.* & Mao, T.* (2014) A comprehensive thalamocortical projection map at the mesoscopic level. Nature Neuroscience. 17(9):1276-85. (*: co-senior authors)