Babak Javid, MB, PhD

Assoc Professor In Residence
Medicine
Research Overview: 

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is the world's most deadly infectious disease, even now. Despite being curable, progress in the fight against tuberculosis (TB) has been slow: treatment takes at least 6 months of taking multiple antibiotics, and the only available vaccine doesn’t protect most people.  In the Javid lab, we strongly believe that studying the fundamental biology of Mtb is necessary before we can improve current treatment and preventative strategies.

In addition to our focus on TB, our lab has an interest in regulation of gene translation in other systems: including unique aspects of the translational apparatus in human beings. We welcome expressions of interest from curious, passionate people who want to join us in a collaborative journey of discovery.

Regulation of adaptive translation and mistranslation

Genetic information needs to be translated into functional proteins. We have shown that this 'information pathway' is prone to error - but surprisingly, pathogens such as Mtb use error-prone translation, mistranslation, as a mechanism to adapt to hostile environments, such as antibiotics and host immunity. In addition to studying 'adaptive mistranslation', we are investigating other mechanisms by which regulation of protein synthesis can allow adaptation in both pathogens and in humans.

Mechanisms of tuberculosis antibiotic tolerance

Not all bacteria in a drug-susceptible isogenic population respond the same to antibiotics: some subpopulations are killed more slowly, or not all, and this is termed antibiotic tolerance. Antibiotic tolerance is thought to be the reason that tuberculosis treatment takes at least 6 months, and even then, a significant proportion of patients relapse – without developing drug resistance. We have recently identified a number of molecular mechanisms that cause tolerance to the first-line anti-TB drug rifampicin, as well as novel therapeutics targeting tolerant subpopulations.

Human humoral immunity to tuberculosis

We and others have recently re-examined the role of antibody-mediated immunity to tuberculosis. Although animal studies had suggested it may not be very important, we chose to look specifically in human beings. We study highly exposed individuals, e.g. healthcare works in busy TB hospitals, and have shown that a proportion of them make antibody responses that protect against Mtb both in vitro and in animal models. In collaboration, we have now isolated monoclonal antibodies (mAbs) that show protection, and we are currently investigating the mechanisms by which they do so. Our work will inform both rational vaccine design, as well as investigate the potential for protective mAbs as adjunct therapeutics.

Primary Thematic Area: 
Virology & Microbial Pathogenesis
Secondary Thematic Area: 
Immunology
Research Summary: 
Fundamental mycobacterial physiology and host pathogen-interactions.

Websites

Featured Publications: 

Covid-19: should the public wear face masks?

BMJ (Clinical research ed.)

Javid B, Weekes MP, Matheson NJ

Selective translation by alternative bacterial ribosomes.

Proceedings of the National Academy of Sciences of the United States of America

Chen YX, Xu ZY, Ge X, Sanyal S, Lu ZJ, Javid B

Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription.

Nature communications

Zhu JH, Wang BW, Pan M, Zeng YN, Rego H, Javid B

Kasugamycin potentiates rifampicin and limits emergence of resistance in Mycobacterium tuberculosis by specifically decreasing mycobacterial mistranslation.

eLife

Chaudhuri S, Li L, Zimmerman M, Chen Y, Chen YX, Toosky MN, Gardner M, Pan M, Li YY, Kawaji Q, Zhu JH, Su HW, Martinot AJ, Rubin EJ, Dartois VA, Javid B

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis.

Proceedings of the National Academy of Sciences of the United States of America

Li H, Wang XX, Wang B, Fu L, Liu G, Lu Y, Cao M, Huang H, Javid B

Antibodies and tuberculosis: finally coming of age?

Nature reviews. Immunology

Li H, Javid B