曾文文

Professional Experience

1998 - 2002  B.S., Biological Sciences, Tsinghua University, China

2003 - 2009  Ph.D., The University of Texas Southwestern Medical Center, USA (Mentor: Zhijian "James" Chen, Ph.D.)

2009 - 2011  Postdoctoral Research Fellow, Department of Discovery Immunology, Genentech Inc., USA (Mentor: Harinder Singh, Ph.D.)

2011 - 2014  Postdoctoral Fellow, Howard Hughes Medical Institute, Laboratory of Molecular Genetics, The Rockefeller University, USA (Mentor: Jeffrey M. Friedman, Ph.D.)

2014 -  present Principal Investigator, School of Medicine & Institute for Immunology, Tsinghua, University, China

2018 -  present Associate director, Beijing Key Lab for Immunological Research on Chronic Diseases

2020 -  present Associate Professor (Tenured), School of Medicine & Institute for Immunology, Tsinghua, University, China

 

Recognitions and Awards

2018  The National Science Fund for Excellent Young Scholar

2018  Young Investigator Award, Lipid Metabolism and Bioenergetics Subsociety of the Biophysical Society of China

2016  Outstanding Young Scholar Award, Qiu-Shi Science & Technologies Foundation

2015  National Young Investigator Award

 

Academic Activities

2020-present  Editorial board member, Oxford Open Immunology

 

Research Interest

The research interest in the Zeng lab is to explore the molecular mechanisms of energy homeostasis and diseases to better understand fundamental biological processes. Currently, our major direction is energy balance, including metabolic homeostasis and diseases, neural and immune regulation of metabolism and neuro-inflammation. Understanding these processes may provide key insights into the therapeutics of metabolic related diseases, including obesity, diabetes, and immunological disorders.

Topics of Research

Energy balance

 

Efferent signals from the central nervous system represent a key layer of regulation of white adipose tissue (WAT). We exploit the volume fluorescence-imaging technique to visualize the neural arborizations in mouse inguinal WAT at single-fiber resolution. The imaging reveals a dense network of sympathetic arborizations that had been previously undetected by conventional methods, with sympathetic fibers being in close apposition to > 90% of adipocytes. We demonstrate that these sympathetic fibers originate from the celiac ganglia, which are activated by cold challenge. Sympathetic-specific deletion of TrkA receptor or pharmacologic ablation by 6-hydroxydopamine abolishes these intra-adipose arborizations and, as a result, cold-induced beiging of inguinal WAT. Furthermore, we find that local sympathetic arborizations function through beta-adrenergic receptors in this beiging process. These findings uncover an essential link connecting efferent neural signals with metabolism of individual adipocytes.

Jiang H, Ding X, Cao Y, Wang H, Zeng W. Dense Intra-adipose Sympathetic Arborizations Are Essential for Cold-Induced Beiging of Mouse White Adipose Tissue. Cell Metab. 2017 Oct 3;26(4):686-692.e3. doi: 10.1016/j.cmet.2017.08.016.

 

Neuroinflammation

 

Neuroinflammation is a crucial mechanism in many neurological disorders. Injury to the peripheral sensory nerves leads to a neuroinflammatory response in the somatosensory pathway, from dorsal root ganglia (DRG) to the spinal cord, contributing to neuropathic pain. We find that ciliary neurotrophic factor (CNTF), highly expressed in Schwann cells, mediates neuroinflammatory response through the activating signal transducer and activator of transcription 3 (STAT3) and inducing interleukin 6 (IL-6) in sensory neurons. Cntf deficiency attenuates neuroinflammation in DRG and the spinal cord with alleviated pain post-injury. Recombinant CNTF applied to the sensory nerves recapitulates neuroinflammation in the DRG and spinal cord, with consequent pain development. We delineate the CNTF-STAT3-IL-6 axis in mediating the onset and progression of the inflammatory cascade from the periphery to the spinal cord with therapeutic implications for neuropathic pain.

Hu Z, Deng N, Liu K, Zhou N, Sun Y, Zeng W. CNTF-STAT3-IL-6 Axis Mediates Neuroinflammatory Cascade across Schwann Cell-Neuron-Microglia. Cell Rep. 2020 May 19;31(7):107657. doi: 10.1016/j.celrep.2020.107657.

We find that dual leucine zipper kinase (DLK) is required for the neuronal intrinsic immune response to induce cytokines and chemokines such as Ccl2, Ccl7, and Ccl12 upon nerve injury. The DLK-controlled injury response in sensory neurons could regulate CD11b+ immune cell infiltration in the dorsal root ganglia, as well as microgliosis and astrogliosis in the spinal dorsal horn but not the ventral horn. Deficiency of Dlk drastically alleviates the neuropathic pain elicited by chronic constriction injury of the sciatic nerve. Thus, DLK is an essential component that mediates the neuronal intrinsic immune response to nerve injury in sensory neurons and regulates inflammation in the spinal cord.

Hu Z, Deng N, Liu K, Zeng W. DLK mediates the neuronal intrinsic immune response and regulates glial reaction and neuropathic pain. Exp Neurol. 2019 Dec;322:113056. doi: 10.1016/j.expneurol.2019.113056. Epub 2019 Sep 5.

 

Publications

ORCID: 0000-0001-8544-3318

 

ResearcherID: D-7276-2017

 

Selected Publications (#corresponding author and lead author, *equal contribution):

 

Sui, Y., and Zeng, W.# (2020). MS4A4A Regulates Arginase 1 Induction during Macrophage Polarization and Lung Inflammation in Mice. Eur J Immunol 50, 1602-1605.

Meng, X., Zeng, W., Young, S.G.#, and Fong, L.G. (2020). GPIHBP1, a partner protein for lipoprotein lipase, is expressed only in capillary endothelial cells. J Lipid Res 61, 591.

Hu, Z.*, Deng, N.*, Liu, K., Zhou, N., Sun, Y., and Zeng, W.# (2020). CNTF-STAT3-IL-6 Axis Mediates Neuroinflammatory Cascade across Schwann Cell-Neuron-Microglia. Cell Rep 31, 107657.

Hu, Z., Deng, N., Liu, K., and Zeng, W.# (2019). DLK mediates the neuronal intrinsic immune response and regulates glial reaction and neuropathic pain. Exp Neurol 322, 113056.

Hu, Z., and Zeng, W.# (2018). Splenic Leukocytes Get the Nerves up for Myelopoiesis. Immunity 49, 1-3.

Zhang, S., Li, N., Zeng, W., Gao, N.#, and Yang, M.# (2017). Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism. Protein Cell 8, 834-847.

Jiang, H.*, Ding, X.*, Cao, Y., Wang, H., and Zeng, W.# (2017). Dense Intra-adipose Sympathetic Arborizations Are Essential for Cold-Induced Beiging of Mouse White Adipose Tissue. Cell Metab 26, 686-692 e683.

Zeng, W.*, Pirzgalska, R.M.*, Pereira, M.M., Kubasova, N., Barateiro, A., Seixas, E., Lu, Y.H., Kozlova, A., Voss, H., Martins, G.G., Friedman, J.M.#, Domingos, A.I.# (2015). Sympathetic neuro-adipose connections mediate leptin-driven lipolysis. Cell 163, 84-94.

Zeng, W.*, Lu, Y.H.*, Lee, J., and Friedman, J.M.# (2015). Reanalysis of parabiosis of obesity mutants in the age of leptin. Proc Natl Acad Sci U S A 112, E3874-3882.

Peng, Y.*, Zeng, W.*, Ye, H., Han, K.H., Dharmarajan, V., Novick, S., Wilson, I.A., Griffin, P.R., Friedman, J.M., and Lerner, R.A.# (2015). A General Method for Insertion of Functional Proteins within Proteins via Combinatorial Selection of Permissive Junctions. Chem Biol 22, 1134-1143.

Glasmacher, E.*, Agrawal, S.*, Chang, A.B.*, Murphy, T.L.*, Zeng, W.*, Vander Lugt, B., Khan, A.A., Ciofani, M., Spooner, C.J., Rutz, S., Hackney, J., Nurieva, R., Escalante, C.R., Ouyang, W., Littman, D.R., Murphy, K.M.#, Singh, H.# (2012). A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science 338, 975-980.

Rutz, S., Noubade, R., Eidenschenk, C., Ota, N., Zeng, W., Zheng, Y., Hackney, J., Ding, J., Singh, H., and Ouyang, W.# (2011). Transcription factor c-Maf mediates the TGF-beta-dependent suppression of IL-22 production in T(H)17 cells. Nat Immunol 12, 1238-1245.

Zeng, W.*, Sun, L.*, Jiang, X., Chen, X., Hou, F., Adhikari, A., Xu, M., and Chen, Z.J.# (2010). Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell 141, 315-330.

Zeng, W., Xu, M., Liu, S., Sun, L.#, and Chen, Z.J.# (2009). Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3. Mol Cell 36, 315-325.

Xu, M., Skaug, B., Zeng, W., and Chen, Z.J.# (2009). A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNFalpha and IL-1beta. Mol Cell 36, 302-314.

Xia, Z.P., Sun, L., Chen, X., Pineda, G., Jiang, X., Adhikari, A., Zeng, W., and Chen, Z.J.# (2009). Direct activation of protein kinases by unanchored polyubiquitin chains. Nature 461, 114-119.

Zeng, W., and Chen, Z.J.# (2008). MITAgating viral infection. Immunity 29, 513-515.

Yang, M., Xu, G., Li, S., Sun, L., Shi, N., Zeng, W., Pang, H., Zhang, W., and Rao, Z.# (2003). Crystallization and preliminary crystallographic analysis of the extracellular fragment of FcalphaRI/CD89. Acta Crystallogr D Biol Crystallogr 59, 2251-2253.

Sun, Z.H., Lai, Y.L., Zeng, W., Zhao, D., Zuo, H.C., and Xie, Z.P.# (2003). Neural stem/progenitor cells survive and differentiate better in PD rats than in normal rats. Acta Neurochir Suppl 87, 169-174.

 

Sun, Z.H., Lai, Y.L., Zeng, W., Zhao, D., Ye, Z.W., Zuo, H.C., and Xie, Z.P.# (2003). Mesencephalic progenitors can improve rotational behavior and reconstruct nigrostriatal pathway in PD rats. Acta Neurochir Suppl 87, 175-180.