Dijun Du    Assistant Professor, PI
InstituteSchool of Life Science and Technology
Research AreaStructural Biology of membrane transporters
Contact Info.dudj@@shanghaitech.edu.cn


Biography
1986-1991 B.S.at Tongji Medical  University
1991-1996 Resident physician at Department of Rheumatology,  China-Japan Friendship Hospital
1996-1999 M.S. at Beijing Institute of  Geriatrics of Ministry of Health
1999-2002 Attending physician at Department  of Pulmonary Disease, Beijing Hospital
2002-2007 Ph.D. at School of  Biological and Biomedical Science, University of Durham
2007-2008 Research  Associate at Structural Genomics Consortium, University of Oxford
2008-2018  Research Associate at Department of Biochemistry, University of  Cambridge
2018.9- Assistant Professor, PI at School of Life Science and  Technology, ShanghaiTech University

Research  Interests
Chronic pain is a rising health problem  that afflicts ~10% of the population. There are several different classes of  chronic pain, including inflammatory pain following tissue injury, neuropathic  pain following nerve, spinal cord and brain injury, cancer pain and pain induced  by drug treatment. Chronic pain is typically characterized by hyperalgesia and  allodynia, which results from altered neuronal activity. The development of  neuroinflammation is responsible for generating and sustaining the sensitization  of nociceptive neurons that leads to chronic pain. Neuroinflammation occurs in  the peripheral and central nervous system, and is characterized by infiltration  of leukocytes and increased production of inflammatory mediators at these sites.  In the peripheral neuroinflammation, inflammatory mediators activate several  kinases, which cause peripheral sensitization through the modulation of key  transduction molecules such as transient receptor potential (TRP) cation  channels TRPA1, TRPV1 and TRPM8, as well as key conduction molecules such as the  voltage-gated sodium channels Nav1.7, Nav1.8 and Nav1.9. Currently, the  treatment of intractable neuropathic pain still relies on classical analgesics,  including morphine or antiepileptic drugs, which have limited efficacy and  numerous side effects. Targeting the processes and molecules that are involved  in neuroinflammation could lead to better treatments for chronic  pain.

Antibiotic resistance of pathogenic bacteria is a growing clinical  problem, exacerbated by insufficient development of new antibiotics. Drug efflux  pumps in the bacterial cell envelope play important roles in intrinsic or  acquired drug resistance to a wide variety of currently available antimicrobial  agents, which is one of the major causes of multidrug resistance. The lack of  structural and mechanistic information has hindered the development of drugs to  block these pumps.

Our group is interested in the elucidation of the  structure and mechanism of chronic pain related ion channels, as well as  tripartite multidrug efflux pumps of Gram-negative pathogenic bacteria, using  cryo-electron microscopy and X-ray crystallography, as well as other biophysics  and biochemistry methods. This information will guide structure-based drug  design.


Selected  Publications

1. Du D, Wang-Kan X, Neuberger A, van Veen HW, Pos KM,  Piddock LJV, Luisi BF. Multidrug efflux pumps: structure, function and  regulation. Nat Rev Microbiol. 2018, 16(9):523-539.


2. Neuberger A, Du D, Luisi BF. Structure and  mechanism of bacterial tripartite efflux pumps. Res Microbiol.  2018, pii: S0923-2508(18)30075-5.


3. Du D, Wang Z, Chiu W, Luisi BF. Purification  of AcrAB-TolC Multidrug Efflux Pump for Cryo-EM Analysis. Methods  Mol Biol. 2018, 1700:71-81.


4. Bruce HA, Du D, Matak-Vinkovic D, Bandyra KJ,  Broadhurst RW, Martin E, Sobott F, Shkumatov AV, Luisi BF. Analysis of  the natively unstructured RNA/protein-recognition core in the Escherichia coli  RNA degradosome and its interactions with regulatory RNA/Hfq  complexes. Nucleic Acids Res. 2018, 46(1):387-402.


5. Fitzpatrick AWP, Llabrés S, Neuberger A, Blaza JN, Bai XC, Okada U,  Murakami S, van Veen HW, Zachariae U, Scheres SHW*, Luisi BF*, Du  D*.  Structure of the MacAB-TolC ABC-type tripartite multidrug  efflux pump. Nat Microbiol. 2017, 2:17070 (*Corresponding  authors).


6. Wang Z, Fan G, Hryc CF, Blaza JN, Serysheva II, Schmid MF, Chiu W*,  Luisi BF*, Du D*.  An allosteric transport mechanism  for the AcrAB-TolC multidrug efflux pump. Elife. 2017, 6. pii:  e24905. doi: 10.7554/eLife.24905 (*Corresponding authors).


7. Du D, van Veen HW, Murakami S, Pos KM, Luisi BF.  Structure, mechanism and cooperation of bacterial multidrug  transporters.Curr Opin Struct Biol. 2015,  33:76-91. doi: 10.1016/j.sbi.2015.07.015.


8. Du D, Voss J, Wang Z, Chiu W, Luisi BF. The  pseudo-atomic structure of an RND-type tripartite multidrug efflux  pump Biol Chem. 2015, 396:1073-82.   


9. Du D, van Veen HW, Luisi BF. Assembly and  operation of bacterial tripartite multidrug efflux pumps. Trends  Microbiol. 2015, 23(5): 311-9.


10. Du D*, Wang Z, James NR, Voss JE, Klimont E,  Ohene-Agyei T, Venter H, Chiu W, Luisi BF*. Structure of the AcrAB-TolC  multidrug efflux pump. Nature. 2014, 509 (7501): 512-5  (*Corresponding authors). 


11. Grüning NM, Du D, Keller MA, Luisi BF, Ralser M.  Inhibition of triosephosphate isomerase by phosphoenolpyruvate in the  feedback-regulation of glycolysis. Open Biol. 2014, 4:130232.  


12. Du D, Venter, H, Pos, K.M. and Luisi, BF.  The Machinery and Mechanism of Multidrug Efflux in Gram-negative  Bacteria. Microbial Efflux Pumps: Current Research. 2013.  Chapter 3.


13. Tsai YC, Du D, Domínguez-Malfavón L,  Dimastrogiovanni D, Cross J, Callaghan AJ, García-Mena J, Luisi BF.  Recognition of the 70S ribosome and polysome by the RNA degradosome in  Escherichia coli. Nucleic Acids Res. 2012, 40(20):10417-31  


14. Nurmohamed S, Vincent HA, Titman CM, Chandran V, Pears MR, Du  D, Griffin JL, Callaghan AJ, Luisi BF. Polynucleotide  phosphorylase activity may be modulated by metabolites in Escherichia  coli. J Biol Chem. 2011, 286(16):14315-23.


15. Federici L+, Du D+, Walas F,  Matsumura H, Fernandez-Recio J, McKeegan KS, Borges-Walmsley MI, Luisi BF,  Walmsley AR: The crystal structure of the outer membrane protein VceC  from the bacterial pathogen Vibrio cholerae at 1.8 Å resolution. J  Biol Chem. 2005, 280: 15307-15314 (+Equal contributions).


16. Borges-Walmsley MI, Du D, McKeegan KS, Sharples GJ,  Walmsley AR: VceR regulates the vceCAB drug efflux pump operon of Vibrio  cholerae by alternating between mutually exclusive conformations that bind  either drugs or promoter DNA. Journal of Molecular Biology,  2005, 349:387-400.


17. Miao J, Du D: The effect of therapeutic  intervention with corticosteroids on outcome and prognosis of  sarcoidosis. Chinese Journal of Tuberculosis and Respiratory  Diseases, 2003, 26:14-17.


18. Du D, Miao J, Zhang X: Construction and  application of Escherichia coli strains used as internal control for competitive  PCR. Chinese Journal of Microbiology and Immunology, 2000,  20:442-446.


19. Hu Y, Du D, Zhang X: Escherichia coli of  ESBL in urinary tract infection resistance and typing by Pulsed-filed Gel  electrophoresis. Chinese Journal of Nosocomiology, 2000,  10:154-155. 


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