Dekai Zhang, MD

Biography

Education and Training

Dekai Zhang earned his M.S. and M.D. in Internal Medicine at Harbin Medical University and his Ph.D. in Cancer and Cell Biology at the University of Hong Kong. He undertook postdoctoral studies for Cancer Research and Immunobiology at Yale University School of Medicine, the Howard Hughes Medical Institute. Before he joined the IBT in September 2005, he was a Research Associate Scientist in the Department of Immunobiology at Yale University. Currently, he is an Associate Professor in the Center for Infectious and Inflammatory Diseases at the Institute of Biosciences & Technology, Texas A&M University Health Science Center.

Research Interests

Our laboratory has been studying innate immunity by identifying novel pattern-recognized receptors (PRRs) and determining their functional mechanism in different diseases. We have developed comprehensive approaches to study how innate receptors recognize their ligands to activate specific signaling pathways and trigger unique, innate immune responses in different infectious diseases and cancers. We are particularly interested in one family of PRRs, the Toll-like receptors (TLRs), which are critical in initiating innate immune responses. We wish to understand the mechanisms by which TLRs recognize different pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).  We have been working on determining the specific regulatory mechanisms of TLR signal pathways that lead to NF-kB and IFN activation in different diseases. Recently our lab has been focusing on some translation research: 1) to discover a new strategy by modulating immune response against infectious diseases; 2) to develop a novel strategy to treat and prevent cancer by studying the important links between infection, inflammation, and cancer.

Ten Most Significant Publications

1.  Zhang D., Zhang GL, Hayden MS, Greenblatt M, Bussey C., Flavell R., and Ghosh S. A novel Toll-like receptor that prevents infection by uropathogenic bacteria. Science. 2004 Mar 5; 303(5663):1522-6. 

   1. (Highly cited) esi-topics.com/nhp/2005/may-05-Ghosh_Hayden_Zhang.html

2. Yarovinsky F., Zhang D., Andersen J., Bannenberg GL., Serhan C., Hieny S., Flavell RA., Ghosh S., Sher A. TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 2005 Jun 10; 308(5728):1626-9.

3. Rao P, Hayden M, Long M, Scott M, West P, Zhang D, Lynch C, Hoffman A, Baltimore D, Oeckinghaus A, Ghosh S. IκBβ acts to both inhibit and activate gene expression at different stages of the inflammatory response. Nature 2010 466(7310):1115-9. PMID: 20740013

4. Cai Z, Sanchez A, Shi Z, Zhang T, Zhang D.* Activation of Toll-Like Receptor 5 on Breast Cancer Cells by Flagellin Suppresses Cell Proliferation and Tumor Growth. Cancer Res. 2011 Apr 1;71(7):2466-75. PMID: 21427357

5. Mathur R, Oh H, Zhang D, Park SG, Seo J, Koblansky A, Hayden MS, Ghosh S. A mouse model of salmonella typhi infection. Cell. 2012 Oct 26;151(3):590-602. PMID: 23101627

6. Song W, Wang J, Han Z, Zhang Y, Zhang H, Wang W, Chang J, Xia B, Fan S, Zhang D, Wang J, Wang HW, Chai J. Structural basis for specific recognition of single-stranded RNA by Toll-like receptor 13. Nat Struct Mol Biol. 2015 Oct;22(10):782-7. PMID: 26323037.

7. Shi M, Zhang Y, Liu L, Zhang T, Han F, Cleveland J, Wang F, McKeehan WL, Li Y, Zhang D*. MAP1S Protein Regulates the Phagocytosis of Bacteria and Toll-like Receptor (TLR) Signaling. J Biol Chem. 2016 Jan 15;291(3):1243-50. PMID: 26565030.

8. Khan A, Bakhru P, Saikolappan S, Das K, Soudani E, Singh CR, Estrella JL, Zhang D, Pasare C, Ma Y, Sun J, Wang J, Hunter RL, Tony Eissa N, Dhandayuthapani S, Jagannath C. An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice. NPJ Vaccines. 2019;4:34. PMID: 31396406.

9. Fan Y, Li Y, Chu Y, Liu J, Cui L, Zhang D*. Toll-Like Receptors Recognize Intestinal Microbes in Liver Cirrhosis. Front Immunol. 2021 Feb 23;12:608498. PMID: 33708204

10. Hoden B, DeRubeis D, Martinez-Moczygemba M, Ramos KS, Zhang D*. Understanding the role of Toll-like receptors in lung cancer immunity and immunotherapy. Front Immunol. 2022 Oct 31;13:1033483. doi: 10.3389/fimmu.2022.1033483. PMID: 36389785

Selected Publications

Additional Selected Publications

1. Fan Y, Li Y, Chu Y, Liu J, Cui L, Zhang D*. Toll-Like Receptors Recognize Intestinal Microbes in Liver Cirrhosis. Front Immunol. 2021 Feb 23;12:608498. PMID: 33708204

2. Liu J, Wang Y, Chu Y, Xu R, Zhang D*, Wang X*. Identification of a TLR-Induced Four-lncRNA Signature as a Novel Prognostic Biomarker in Esophageal Carcinoma. Front Cell Dev Biol. 2020;8:649.  PMID: 32850794.

3. Chu Y, Liu Z, Liu J, Yu L, Zhang D*, Pei F*. Characterization of lncRNA-Perturbed TLR-Signaling Network Identifies Novel lncRNA Prognostic Biomarkers in Colorectal Cancer. Front Cell Dev Biol. 2020;8:503.  PMID: 32626715.

4. Lu Y, Li X, Liu S, Zhang Y, Zhang D*. Toll-like Receptors and Inflammatory Bowel Disease. Front Immunol. 2018;9:72.  PMID: 29441063.

5. Sun L, Li Y, Jia X, Wang Q, Li Y, Hu M, Tian L, Yang J, Xing W, Zhang W, Wang J, Xu H, Wang L, Zhang D*, Ren H*. Neuroprotection by IFN-γ via astrocyte-secreted IL-6 in acute neuroinflammation. Oncotarget. 2017 Jun 20;8(25):40065-40078.  PMID: 28454116.

6. Jing Y, Liang H, Zhang Y, Cleveland J, Yan J, Zhang D*. Up-regulation of Toll-like Receptor 9 in Osteosarcoma. Anticancer Res. 2015 Nov;35(11):5839-43. PubMed PMID: 26504005.

7. Zhao S, Zhang Y, Zhang Q, Wang F, Zhang D*. Toll-like receptors and prostate cancer. Front Immunol. 2014;5:352. PMID: 25101092.

8. Fan Y, Mao R, Yu Y, Liu S, Shi Z, Cheng J, Zhang H, An L, Zhao Y, Xu X, Chen Z, Kogiso M, Zhang D, Zhang H, Zhang P, Jung JU, Li X, Xu G, Yang J. USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase. J Exp Med. 2014 Feb 10;211(2):313-28. doi: 10.1084/jem.20122844.

9. Du B, Luo W, Li R, Tan B, Han H, Lu X, Li D, Qian M, Zhang D, Zhao Y, Liu M. Lgr4/Gpr48 negatively regulates TLR2/4-associated pattern recognition and innate immunity by targeting CD14 expression. J Biol Chem. 2013 May 24;288(21):15131-41. doi: 10.1074/jbc.M113.455535. PMID: 23589304

10. Shi Z, Cai Z, Zhang T, Zhao S, Smeds E, Zhang Q, Wang F, Fu S, Ghosh S, Zhang D*.  TLR11 Prevents Salmonella’s penetration into the murine Peyer’s Patches, J Biol Chem 2012. Dec 21;287(52):43417-23. doi: 10.1074/jbc.M112.411009. PMID: 23135279

11. Gorjestani S., Yu M., Tang B., Zhang, D., Wang D, Lin X. Phospholipase C-gamma 2 (PLCg2) is a key component in Dectin-2 signaling pathway, mediating anti-fungal innate immune responses. J Biol Chem. 2011 Dec 23; 286:43651-9.

12. Shi Z, Cai Z, Sanchez A, Zhang T, Wen S, Wang J, Yang J, Fu S, Zhang D.* A novel toll-like receptor that recognizes vesicular stomatitis virus. J Biol Chem. 2010 Dec 3.

13. Sengupta, D., Koblansky, A., Gaines J., Brown T., West PA, Zhang D., Nishikawa T., Park., Roop MR., Ghosh S. Subversion of innate immune responses by Brucella through the targeted degradation of the TLR signaling adapter, MAL. J Immunol 2010 Jan 15;184(2):956-64. PMID: 20018612

14. Cai Z, Shi Z, Sanchez A, Zhang T, Liu M, Yang J, Wang F, Zhang D.* Transcriptional regulation of TLR11 gene expression in epithelial cells. J Biol Chem. 2009 Nov 27; 284(48): 33088-96. [Epub ahead of print]. PMID: 19801549

15. Shi Z, Cai Z, Wen S, Chen C, Gendron C, Sanchez A, Patterson K, Fu S, Yang J, Wildman DE, Finnell RH, Zhang D* Transcription regulation of the novel Toll-like receptor TLR13.  J Biol Chem. 2009 Jul 31; 284(31): 20540-7. PMID: 19487701

16. Fan Y, Mao R, Zhao Y, Yu Y, Sun W, Song P, Shi Z, Zhang D, Yvon E, Zhang H, Fu S, Yang J. Tumor necrosis factor-[alpha] induces RelA degradation via ubiquitination at LYS-195 to prevent excessive nuclear factor-[kappa]B activation. J Biol Chem. 2009 Oct 23; 284(43): 29270-7. PMID: 19706600

17. Sun W, Yu Y, Dotti G, Shen T, Tan X, Savoldo B, Pass AK, Chu M, Zhang D, Lu X, Fu S, Lin X, Yang J. PPM1A and PPM1B Act as IKKbeta Phosphatases to terminate TNFalpha-induced NF-kappaB activation. Cell Signal. 2009 Jan;21(1):95-102. Epub 2008 Oct 1.

18. Yu Y,  Ge N, Xie M, Sun W, Burlingame S, Pass AK, Nuchtern JG, Zhang D, Fu S, Schneider MD, Fan J, and Yang Y, Phosphorylation of Thr-178 and Thr-184 in TAK1 T-loop is required for interleukin (IL)-1-mediated optimal NF-kB and AP-1 activations as well as IL-6 gene expression. J Biol Chem. 2008 Sep 5; 283(36):24497-505. PMID: 18617512

19. Cao D., Russell R., Zhang D., Leffert J., and Pizzorno G. Uridine phosphorylase (-/-) murine embryonic stem cells clarify the key role of this enzyme in the regulation of the pyrimidine salvage pathway and in the activation of fluoropyrimidines. Cancer Res. 2002; 62(8):2313-7.

20. Pizzorno G, Cao D, Leffert JJ, Russell RL, Zhang D., Handschumacher RE Homeostatic control of uridine and the role of uridine phosphorylase: a biological and clinical update. Biochim Biophys Acta. 2002, 1587(2-3):133-44.

21. Zhang D., Cao D., Russell R., and Pizzorno G. p53-dependent Suppression of Uridine Phosphorylase Gene Expression through Direct Promoter Interaction. Cancer Res 2001 61: 6899-6905.

22. Russell RL, Cao D, Zhang D., Handschumacher RE, Pizzorno G. Uridine phosphorylase association with vimentin. Intracellular distribution and localization. J Biol Chem 2001; 276(16):13302-7.

23. Yang X, Sham JS, Ng MH, Tsao SW, Zhang D., Lowe SW, Cao L. LMP1 of Epstein-Barr virus induces proliferation of primary mouse embryonic fibroblasts and cooperatively transforms the cells with a p16-insensitive CDK4 oncogene. J Virol. 2000; 74(2):883-91.

24. Cao DL, Immakayalu MA, Wang FY, Zhang D., Handschumacher RE, Bray-Ward P, Pizzorno G., Genomic structure, chromosomal mapping, and promoter region analysis of murine uridine phosphorylase gene. Cancer Res. 1999, 59:4997-5001.

25. Zhang D., Ngan H.Y.S., Cheng R.Y.S., Cheung A.N.Y., Liu S.S., and Tsao S.W., Clinical significance of telomerase activity and telomeric restriction fragment (TRF) in cervical cancer. Eur J Cancer. 1999; 35(1):154-60.

26. Pizzorno G, Cao D, Leffert JJ, Russell RL, Zhang D., Handschumacher RE Homeostatic control of uridine and the role of uridine phosphorylase: a biological and clinical update. Biochim Biophys Acta. 2002, 1587(2-3):133-44.

27. Zhang D., Cao D., Russell R., and Pizzorno G. p53-dependent Suppression of Uridine Phosphorylase Gene Expression through Direct Promoter Interaction. Cancer Res 2001 61: 6899-6905.

28. Russell RL, Cao D, Zhang D., Handschumacher RE, Pizzorno G. Uridine phosphorylase association with vimentin. Intracellular distribution and localization. J Biol Chem 2001; 276(16):13302-7.

29. Yang X, Sham JS, Ng MH, Tsao SW, Zhang D., Lowe SW, Cao L. LMP1 of Epstein-Barr virus induces proliferation of primary mouse embryonic fibroblasts and cooperatively transforms the cells with a p16-insensitive CDK4 oncogene. J Virol. 2000; 74(2):883-91.

30. Cao DL, Immakayalu MA, Wang FY, Zhang D., Handschumacher RE, Bray-Ward P, Pizzorno G., Genomic structure, chromosomal mapping, and promoter region analysis of murine uridine phosphorylase gene. Cancer Res. 1999, 59:4997-5001.

31. Zhang D., Ngan H.Y.S., Cheng R.Y.S., Cheung A.N.Y., Liu S.S., and Tsao S.W., Clinical significance of telomerase activity and telomeric restriction fragment (TRF) in cervical cancer. Eur J Cancer. 1999; 35(1):154-60.