Jun Zhao Laboratory

Research

Overview

Cellular metabolism provides energy and biomass for all biological activities. Cells coordinate metabolic changes to adapt to distinct physiological and pathological conditions such as innate immune activation, viral infection, or tumorigenesis. Meanwhile, emerging evidence indicates that metabolic states can modulate cell signaling, partly through the non-canonical functions of certain metabolic enzymes. We believe that such crosstalk are the inherent bi-directional linkages between cellular metabolism and fundamental biological processes. Evidence has shown that such linkages could be manipulated by viruses and cancers to promote infection and tumorigenesis. As such, dissecting the molecular mechanisms of these interactions will advance basic science and enable the development of novel antiviral/antitumor strategies.

Our current research directions include:

(1)   Protein deamidation-mediated metabolic reprogramming. 

We have identified a cellular nucleotide biosynthetic enzyme that reprograms inflammation and metabolism to support cell proliferation, and are investigating the role of it in cancers and KSHV-associated malignancies.

(2)   Metabolic reprogramming by herpesviruses.

Our work will delineate the molecular mechanism by which viral proteins manipulate host metabolism to support viral persistent infection and viral oncogenesis.

(3)   Interactions between innate immune signaling and metabolic enzymes. 

We are exploring metabolic enzymes that possess moonlighting activities to regulate innate immune signaling molecules such as RIG-I, cGAS, and NF-κB transcription factors. Meanwhile, we are interested in studying how these enzymes are regulated upon innate immune activation.

Selected Publications

View publications for Jun Zhao, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)

Huang H, Zhao J, Wang TY, Zhang S, Zhou Y, Rao Y, Qin C, Liu Y, Chen Y, Xia Z, Feng P. (2021) Species-specific deamidation of RIG-I reveals collaborative action between viral and cellular deamidases in HSV-1 lytic replication. mBio 2021 Mar 30;12(2):e00115-21.

Zhao J, Tian M, Zhang S, Delfarah A, Gao R, Rao Y, Savas A.C., Lu A, Bubb L, Lei X, Moshirian R, Zhu W, Peng C, Jiang T, Chen L, Graham N.A., Feng P. (2020) Deamidation shunts RelA from mediating inflammation to aerobic glycolysis. Cell Metabolism 2020 May 5;31(5):937-955.e7.

Sun X*, Liu T*, Zhao J*, Xia H, Xie J, Guo Y, Zhong L, et al. (2020) DNA-PK deficiency potentiates cGAS-mediated antiviral innate immunity. Nature Communications 2020 Dec 3;11(1):6182. * co-first author

Zhang J, Zhao J, Li J, Xu S, He S, Zeng Y, Xie L, Xie N, Liu T, Lee K, Seo G-J, Chen L, Stabell, A.C, Xia Z, Sawyer S.L, Jung JU, Huang C, and Feng P. (2018) Species-specific deamidation of cGAS facilitates herpes simplex virus 1 lytic replication. Cell Host & Microbe 2018 Aug 8;24(2):234-248.e5.

Zhao J, Zeng Y, Xu SM, Chen J, Shen G, Yu C, Peng J, Knipe DM, Yuan WM, Xu WQ, Zhang C, Xia Z, and Feng P. (2016) A viral deamidase targets RIG-I to block RNA-induced activation. Cell Host & Microbe 2016 Dec 14;20(6):770-784.

Li J, Zhao J, Xu S, Zhang S, Zhang J, Xiao J, Gao R, Tian M, Zeng Y, Lee K, et al. (2019) Antiviral activity of a purine synthesis enzyme reveals a key role of deamidation in regulating protein nuclear import. Science Advances 2019 Oct 9;5(10):eaaw7373. 

He S., Zhao J, He X, Minassian A, Zandi E, Liang C, Jung JU, Zhang X, and Feng P. (2015) Viral pseudo enzymes activate RIG-I via deamidation to evade cytokine production. Molecular Cell 2015 Apr 2;58(1):134-46. 

Zhao J, He S, Minassian A, Li J, Feng P. (2015) Recent advances on viral manipulation of NF-κB signaling pathway. Current Opinion in Virology 2015 Dec;15:103-11.