Senior Scientist, Vollum Institute
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 firstname.lastname@example.org for more information.
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.
- 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 of brain circuits underlies learning and memory.
- 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
Day-Cooney J, Dalangin R, Zhong H#, Mao T#. (2023) Genetically encoded fluorescent sensors for imaging neuronal dynamics in vivo. #Co-senior Authorships. J Neurochem. Feb;164(3):284-308. doi: 10.1111/jnc.15608. Epub 2022 Apr 9. PMID: 35285522.
Ma L, Day-Cooney J, Benavides OJ, Muniak MA, Qin M, Ding JB, Mao T, Zhong H. (2022) Locomotion activates PKA through dopamine and adenosine in striatal neurons. Nature. Nov;611(7937):762-768. doi: 10.1038/s41586-022-05407-4. Epub 2022 Nov 9. PMID: 36352228.
Massengill CI*, Bayless-Edwards L*, Ceballos CC, Cebul ER, Cahill J, Bharadwaj A, Wilson E, Qin M, Whorton MR, Baconguis I, Ye B, Mao T#, Zhong H#. (2022) Sensitive genetically encoded sensors for population and subcellular imaging of cAMP in vivo. *Co-first Authorships. #Co-senior Authorships. Nat Methods. Nov;19(11):1461-1471. doi: 10.1038/s41592-022-01646-5. Epub 2022 Oct 27. PMID: 36303019.
Wang L, Wu C, Peng W, Zhou Z, Zeng J, Li X, Yang Y, Yu S, Zou Y, Huang M, Liu C, Chen Y, Li Y, Ti P, Liu W, Gao Y, Zheng W, Zhong H, Gao S, Lu Z, Ren PG, Ng HL, He J, Chen S, Xu M, Li Y, Chu (2022) A high-performance genetically encoded fluorescent indicator for in vivo cAMP imaging. J. Nat Commun. Sep 12;13(1):5363. doi: 10.1038/s41467-022-32994-7. PMID: 36097007
Wilson EA, Mao T, Zhong H. (2022) Labeling Endogenous Proteins Using CRISPR-mediated Insertion of Exon (CRISPIE). Bio Protoc. Mar 5;12(5):e4343. doi: 10.21769/BioProtoc.4343. eCollection 2022 Mar 5. PMID: 35592602.
Melander JB*, Nayebi A*, Jongbloets BC, Fortin DA, Maozhen Q, Ganguli S#, Mao T#, Zhong H#. (2021) Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and parvalbumin-positive interneurons. *Contributed equally. #Co-correspondence. Cell Reports. 2021 Nov 9;37(6):109972. doi: 10.1016/j.celrep.2021.109972. PMID: 34758304
Massengill CI, Day-Cooney J, Mao T#, Zhong H#. (2021) Genetically encoded sensors towards imaging cAMP and PKA activity in vivo. #Co-senior Authorships. J. Neurosci. Methods 362:109298.
Zhong H, Ceballos CC, Massengill CI, Muniak MA, Ma L, Qin M, Petrie SK, Mao T. (2021) High-fidelity, efficient, and reversible labeling of endogenous proteins using CRISPR-based designer exon insertion. eLife Jun 8; 10:e64911.
Xiong W-H, Qin M, Zhong H. (2021) Myristoylation alone is sufficient for PKA catalytic subunits to associate with the plasma membrane to regulate neuronal functions. Proc. Natl. Acad. Sci. USA 118(15) e2021658118.
Jiang H, Esparza TJ, Kummer TT, Zhong H, Rettig J, Brody DL. (2020) Live neuron high-content screening reveals synaptotoxic activity in Alzheimer mouse model homogenates. Scientific Reports 10:3412.
Jongbloets BC, Ma L, Mao T, Zhong H. (2019) Visualizing Protein Kinase A activity in head-fixed behaving mice using in vivo two-photon fluorescence lifetime imaging microscopy. J. Vis. Exp. Jun 7; (148) doi: 10.3791/59526. Watch the video article at JoVE
Okawa H, Yu WQ, Matti U, Schwarz K, Odermatt B, Zhong H, Tsukamoto Y, Lagnado L, Rieke F, Schmitz F, Wong ROL. (2019) Dynamic assembly of ribbon synapses and circuit maintenance in a vertebrate sensory system. Nature Commun. 10:2167.
Patriarchi T, Cho JR, Merten K, Howe MW, Marley A, Xiong WH, Folk RW, Broussard GJ, Liang R, Jang MJ, Zhong H, Dombeck D, von Zastrow M, Nimmerjahn A, Gradinaru V, Williams JT, Tian L. (2018) Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. Science 360:eaat4422.
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 99:665-679.e5. *Co-senior authorship
Tillo SE, Xiong WH, Takahashi M, Miao S, Andrade AL, Fortin DA, Yang G, Qin M, Smoody BF, Stork PJS, Zhong H. (2017) Liberated PKA catalytic subunits associate with the membrane via myristoylation to preferentially phosphorylate membrane substrates. Cell Reports 19:617-629.
Shi W, Xianyu A, Han Z, Tang X, Li Z, Zhong H, Mao T, Huang K, Shi SH. (2017) Ontogenetic establishment of order-specific nuclear organization in the mammalian thalamus. Nature Neurosci. 20:516-528.
Hunnicutt BJ, Jongbloets BC, Birdsong WT, Gertz KJ, Zhong H, Mao T. (2016) A comprehensive excitatory input map of the striatum reveals novel functional organization. Elife 5:e19103.
Zhong H. (2015) Applying superresolution localization-based microscopy to neurons. Synapse 69:283-294.
Fortin DA, Tillo SE, Yang G, Rah JC, Melander JB, Bai S, Soler-Cedeño O, Qin M, Zemelman BV, Guo C, Mao T*, Zhong H*. (2014) Live imaging of endogenous PSD-95 using ENABLED: a conditional strategy to fluorescently label endogenous proteins. J. Neurosci. 34:16698-16712. *Co-senior authorship
Hunnicutt BJ, Long BR, Kusefoglu D, Gertz KJ, Zhong H*, Mao T*. (2014) A comprehensive thalamocortical projection map at the mesoscopic level. Nature Neurosci. 17:1276-1285. *Co-senior authorship
Zhong H. (2010) Photoactivated localization microscopy (PALM): an optical technique for achieving ~10-nm resolution. Cold Spring Harb. Protoc. 2010(12):pdb.top91.
Zhong H, Sia GM, Sato TR, Gray NW, Mao T, Khuchua Z, Huganir RL, Svoboda K. (2009) Subcellular dynamics of type II PKA in neurons. Neuron 62:363-374.
Zhong H, Lai J, Yau KW. (2003) Selective heteromeric assembly of cyclic nucleotide-gated channels. Proc. Natl. Acad. Sci. USA 100:5509-5513.
Zhong H, Molday LL, Molday RS, Yau KW. (2002) The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry. Nature 420:193-198.