Principal Investigator
Principal Investigator
Name:Tianyu Zhang
Professional:Principal Investigator
Email:zhang_tianyu@gibh.ac.cn
Address:No.190 Kaiyuan Road, Guangzhou Science Park, Luogang District, Guangzhou 510530
Study/Work Experience


2012.02now

Tuberculosis Lab,State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health , Chinese Academy of Sciences /Direction Leader

2010.09now

Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences / Principal Investigator

2005.102010.08

Johns Hopkins University/Post-doctoral fellow

2002.092005.07

The Chinese Academy of Medical Sciences &The Peking Union Medical College/Ph.D

1999.092002.07

Capital Normal University/M.S

1995.091999.07

Capital Normal University/B.S


Research Areas

Dr. Zhang’s research areas are: 1) Discovery and development of antibacterial agents by special models developed by his group, especially for antimycobacterial drugs.2)Mycobacterial (and other bacterial) genetic manipulations and the mechanisms of action and resistance of antibiotics. 3) Diagnosis of live mycobacteria in clinical samples and test the drug susceptibility efficiently using clinical isolates. 4) Therapeutic tuberculosis vaccine (s).5)Functional Genomics of mycobacteria. 6) Pharmacogenomics of antibiotics.

Academic Performance

 

    Since 2002, DrZhang's research has focused on microbiology, especially on actinomyces which includes streptomyces, mycobacteria etc. During his study in Johns Hopkins University Tuberculosis Research Center from 2005 to 2010, his research focused on the development and use of in vitro and animal models of mycobacterial infections for drug development under the supervision of Drs Nuermberger and Grosset, the late tuberculosis research Chairman in WHO. He also learned genetic approaches from Dr. Bishai during the same time. He constructed autolummescent Mtb and M. ulcerans strains respectively, and found that use of these reporter strains have the potential to drastically reduce the time, effort, animals and resources in the evaluation of drug activity in vitro and  in vivo in live mice. He also refined a mouse model of latent tuberculosis (TB) to increase its predictive value and using it to demonstrate the promise of daily rifapentine-containing regimens for ultra-short treatment of latent TB infection and later TMC207(bedaquiline) -containing regimens for potential treatment of latent MDR-TB infection. National Institute of Allergy and Infectious Diseases (NIAID) released a piece of breaking news on March 5th, 2018 to show that “One-Month Tuberculosis Prophylaxis as Effective as Nine-Month Regimen for People Living with HIV”. This clinical phase III study was based on his animal work.

    He was recruited to GIBH after completing his fellowship at Johns Hopkins University in September, 2010.His research focuses on physiology of Mtb with a focus on developing new drugs against TB. Tens of chemistry groups all over the world come to collaborate with his lab. They also created a selectable marker-free M. abscess using a new system.They have had very good collaboration with all of them. One good example is that they have co-developed an antituberculosis drug candidate, TB47, and sold it to a company in Dec 2015. His lab was responsible for the biological part including the in vitro activity testing against drug-resistant clinical isolates and the in vivo study using virulent Mtb infected mouse model in ABSL-3 lab. They also had cooperative project about antimycobacterial drug discovery with CSIRO (Australia) supported by CAS and CSIRO. A compound showed super powerful activity against M. ulcerans infection, which might shorten the duration from more than two months to about 2-3 weeks. At least four series of compounds from four of their long-term partners showed antituberculosis activity in vivo very recently.

    They verified the Cysl54Arg mutation in the ribosomal protein L3 can cause resistance to oxazolidinone. They found a potential new target of the first-line anti-TB drug pyrazinainide and explained from a new way about the persistence in 2017. They also found mutation ethAW21R Confers Co-resistance to Protionamide and Ethionamide in both M. bovis BCG and M. tuberculosis H37Rv. They have identified several gene mutations which can confer resistance to two new antituberculosis compounds discovered by them very recently using genome sequencing and genetic verification (unpublished)* .

    They also sequenced many clinical drug-resistant M. tuberculosis isolates and found many new mutations related to drug resistance and some clinical drug-resistant isolates show no any known mutations. Recently, they also invented a very efficient tool to detect live mycobacteria in clinical samples and to detect phenotypic susceptibility of mycobacteria to many drugs very quickly.

Representative Papers

1.Yang Liu, Yamin Gao,……, Tianyu Zhang*.The compound TB47 is highly bactericidal against Mycobacterium ulcerans in a Buruli ulcer mouse model. Nature Communications.(Accepted)

2.Mahmudul.M. Islam, Yaoju Tan,……, Tianyu Zhang*. Detection of Novel Mutations Associated with Independent and Cross-resistance to Isoniazid and Protionamide in Mycobacterium tuberculosis Clinical Isolates. Clinical Microbiology and Infection. (Online)

3. Moses Njire, Na Wang,……, Tianyu Zhang*. Pyrazinoic acid inhibits a bifunctional enzyme in Mycobacterium tuberculosis. Antimicrobial Agents and Chmotherapy. 2017 Apr; 61(7): e00070-17

4. Julius Mugweru, Gaelle Makafe, ……, Tianyu Zhang*. A cassette containing thiostrepton, gentamicin resistance genes, and dif sequences is effective in construction of recombinant mycobacteria. Frontiers in Microbiology. 2017 Mar; 8: 468

5. Tianyu Zhang, Siyang Li, ……, Eric L. Nuermberger*. Short-course chemotherapy with TMC207 and rifapentine in a murine model of latent tuberculosis infection. American Journal of Respiratory and Critical Care Medicine. 2011 May; 184: 732-737