Welcome to the Bishai Laboratory Group Website!
Please have a look around and explore our research. My Lab is a member of the Center for Tuberculosis Research at the Johns Hopkins University School of Medicine. We are always receptive to feedback. If our work interests you, or if you are interested in getting involved, please reach-out through the contact page.
Our Areas of Research
Molecular pathogenesis of tuberculosis.
Improved therapies for TB (both anti-bacterial and host-directed therapies).
Pathogenesis of cavitary TB.
Our Specific Research Interests
Our research pivots on using M. tuberculosis
— an intracellular pathogen — as a probe to understand fundamental cell biology and immune defense mechanisms. M. tb.
is phagocytosed by macrophages but manipulates and subverts both the cell and subsequent immune responses to perpetuate its own survival. M. tb.
is an obligate human pathogen. Most commonly it survives in humans by entering a long-lived state of latent infection lasting decades. Later, during aging or immunosuppression it reactivates to cause active disease with significant lung damage and transmissibility to new susceptible human hosts.
In our pathogenesis work, advances include the discovery that M. tb.
secretes pathogen-derived cAMP as well as the STING-agonist cyclic di-AMP into the macrophage cytosol where these second messengers subvert host cell signaling and lead to aberrant immune responses.
In our improved therapies work, we are characterizing several small molecule antibacterials in collaborations with separate chemists. Among our host-directed therapy work has been a focus on cell-depleting diphtheria toxin fusion proteins related to the drug Ontak.
With respect to the pathogenesis of cavity formation, we found that M. tb.
leads to dysregulation of pulmonary matrix metalloproteinase-1 (MMP-1) and cathepsin K (CTSK). These proteases degrade lung type 1 collagen, leading to significant lung damage, cavity formation, and highly transmissible forms of active TB. We have also developed a multiple aerosol exposure model which produces human like cavities in a high proportion of animals in a short period of time. Real-time CT and PET imaging capabilities have enhanced our ability to monitor cavitation.
William R. Bishai, MD, PhD.
Professor, Dept. of Medicine
Division of Infectious Diseases
Co-Director, JHU Center for TB Research