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Tianyu Zhang, Ph.D.
Principal Investigator, Doctoral Advisor

Dr. Zhang Tianyu received his B Sc. in Biology from Capital Normal University, Beijing, China and was recommended for admission to be a postgraduate without exams in 1999. He received his M. Sc. in plant gene engineering in the same university in 2002 and Ph. D from Institute of Medicinal Biotechnology, The Chinese Academy of Medical Sciences &The Peking Union Medical College (PUMC & CAMS). Dr Zhang went to the Johns Hopkins University School of Medicine in USA in 2005.9 as a postdoctoral fellow and then came to Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS) in 2010.09 and then joined the State Key Laboratory of Respiratory Disease in 2011.01.

One third people are infected with tuberculosis (TB) and TB kills 1.7 million in 2009 alone. TB's deadly synergy with HIV/AIDS and a surge in drug-resistant strains are threatening to TB control. At least 1% TB cases (up to 28% in some area) are MDR. The costs of curing MDR-TB can be as much as 1400 times that of regular treatment. The current treatment: combined 4 medicines from 1960s, works only for drug-susceptible TB in 6-9 months. It takes up to 2 years to treat MDR TB patients with second-line drugs often with severe side effects and failure. Some resistant strains are untreatable with any existing antibiotics! BCG, the more than 100-year old vaccine, has questionable effect on TB control.

So there is an urgent need for anti-TB drug/vaccine research and development. Drug-screening and evaluation are highly hampered by the slow-growing of M.TB (3-6 weeks on plates). Tianyu Zhang engineered auto-luminescent M.TB strain and used it to test drugs in vitro and test the drug /vaccine activity noninvasively in vivo. The amazing finding was: the drug effect could be evaluated in 1 to 3 days both in vitro and in vivo. The BCG vaccination effect could be seen in about 3 weeks by monitoring the same batch of mice daily. By enabling serial imaging of the same animal, the use of this reporter strain can also reduce the numbers of animals consumed and improve statistical power. Lower compound requirements, reduced need for BSL-3 animal housing space, and improved laboratory safety through fewer opportunities for handling infected tissues and bacterial aerosolization are additional benefits.




Latent tuberculosis infection murine model of chemotherapy was established successfully by Tianyu Zhang before and short-course LTBI regimens including the first regimen for MDR-LTBI were developed using it. So now we are highly qualified for screening, testing and evaluating drug/vaccine activities.



Personnel: 


Research:
Research Areas
Postgenomics of Mycobacterium tuberculosis; Immunology and the research & development of vaccine of tuberculosis; The research & development of anti-tuberculosis drugs and the study of mechanism of the drug action and drug resistance; Postgenomics of Helicobacter pylori and the research & development of anti-Helicobacter pylori drugs.

Publications: 

1.  Wang J, Lin X, Qin C, Liao S, Wan T, Zhang T, Liu J, Fredimoses M, Chen H, Yang B, Zhou X, Yang X, Tu Z, Liu Y. J Antibiot (accepted)

 

2.  Yang Z, Li R, Zhang T. Evolution of Influenza A H7N9 Virus: More Attention to Gene Constellation. J Genet genomics (accepted)

 

3.  Zhang T, Li SY, Converse PJ, Grosset JH, Nuermberger EL. Rapid, Serial, Non-invasive Assessment of Drug Efficacy in Mice with Autoluminescent Mycobacterium ulcerans Infection. PLoS NTD (accepted)

 

4.  Tan Y, Hu Z, Zhang T*, Cai X, Kuang H, Liu Y, Chen J, Yang F, Zhang K, Tan S*, Zhao Y. Role of pncA and rpsA Gene Sequencing in Diagnosis of Pyrazinamide Resistance in Mycobacterium tuberculosis Isolates from Southern China. J Clin Microbiol , 2013 Oct 16. [Epub ahead of print]

 

5. Liang Z, Zhang K, Tan Y, Tan S, Zhang T*. Rapidly testing the activities of antituberculosis drugs in macrophage using the unmarked autoluminescent Mycobacterium tuberculosis. J Pract Med. (2013), 29(23): 209-212.

 

6. Chen C, Lu M, Liu Z, Wan J, Tu Z, Zhang T*, Ming Yan*. Synthesis and Evaluation of 2-Amino-4H-pyran-3-carbonitrile Derivatives as Antitubercular Agents. O J MED CHEM (2013), 4(3): 128-135

 

7.  Gong Y, Long Q, Xie H, Zhang T, Peng T. Cloning and characterization of human Golgi phosphoprotein 2 gene (GOLPH2/GP73/GOLM1) promoter. Biochem Biophys Res Commun. (2012),421(4):713-720

 

8. Zhang T, Li SY, Nuermberger EL. Autoluminescent Mycobacterium tuberculosis for Rapid, Real-Time, Non-Invasive Assessment of Drug and Vaccine Efficacy. PLoS ONE. (2012), 7(1): e29774.

 

9. Nuermberger EL, Zhang T, Li SY, Williams K, Minkowski A, Andries K, Grosset JH. Efficacy of TMC207 in a Murine Model of Latent Tuberculosis Infection (LTBI). The 2011 Meeting of the American Thoracic Society (ATS ). Am J Respir Crit Care Med.  (2011),183: A4037.

 

10. Zhang T, Li SY, Converse PJAlmeida DV, Grosset JH, Nuermberger EL. Using Bioluminescence to Monitor Treatment Response in Real-time in Mice with Mycobacterium ulcerans Infection. Antimicrob Agents Chemother. (2011), 55(1):56-61.

 

11. Zhang T, Bishai WR, Grosset JH, Nuermberger EL. Rapid assessment of antibacterial activity against Mycobacterium ulcerans by using recombinant luminescent strains. Antimicrob Agents Chemother. (2010),54(7): 2806-2813.

 

12. Zhang T, Zhang M, Rosenthal IM, Grosset JH, Nuermberger EL. Short-course therapy with daily rifapentine in a murine model of latent tuberculosis infection. Am J Respir Crit Care Med. (2009), 180 (11): 1151-1157.

 

13. Nuermberger EL, Zhang T, Zhang M, Grosset JH. Rifapentine-based Regimens Cure Latent Tuberculosis infection (LTBI) in 2 Months or Less in a Mouse Model. The 2009 Meeting of the American Thoracic Society (ATS ). Am J Respir Crit Care Med. (2009), 179: A1017.

 

14. Zhang T, Wang L, Xu G, Chen Y, Zhang Y, Li Y. Disruption of ste23 gene affects composition profile and bioactivity of exopolysaccharide produced by Streptomyces sp. 139. Lett Appl Microbiol. (2006) 42(2) : 132-137.

 

15. Zhang T, Wang L, Xu G, Chen Y, Zhang Y, Li Y. Disruption of the ste22 gene encoding a glycosyltransferase and its function in biosynthesis of Ebosin in Streptomyces sp. 139. Curr Microbiol. (2006) 52(1): 55-59.

 

16. Zhang TY, Wang LY, Jiang R, Li Y. Cloning and expression of UDP-glucose-4-epimerase gene from Streptomyces and characteristics of the enzyme. Wei Sheng Wu Xue Bao. (2005) 45(6): 881-884.

 

专利(Patents)

Eric Nuermberger, Tianyu Zhang, Jacques Grosset: Autoluminescent mycobacterial reporter strains  (2011) (61/367,475).

 

Tianyu Zhang, Feng Yang, Jia Liu. The integrative plasmid pOPHI and unmarked autoluminescent mycobacteria. Patent Number: ZL 201210183007.2 (authorized).

 

Tianyu Zhang, Feng Yang, Wenying Zou. A versatile, resistance expressing cassette for construction of unmarked recombinant mycobacteria high efficiently. Patent Number: 201310386264.0.

 

Qiang Zhu, Tianyu Zhang, Lanying Liu, Minghui Lu, Tingting Mao, Jinbo Huang. Synthesis and preparation methods and application of Indole[3,2-c]-Quinolinols and their acceptable –ate(s) in pharmacy. Patent Number: 201310385431.X.

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