William Ramses Bishai, MD, PhD

Professional Titles

• Co-Director, Johns Hopkins Center for Tuberculosis Research

Primary Academic Title

Professor of Medicine

Background

Centers and Institutes

Global Health, Center for

Additional Academic Titles

Professor of Molecular Biology and Genetics, Joint Appointment in Pathology

Research Interests

Molecular biology of mycobacterium tuberculosis.

Lab Website

William Bishai Laboratory - Lab Website

• The William Bishai Laboratory studies the molecular pathogenesis of tuberculosis. The overall goal of our laboratory is to better understand tuberculosis pathogenesis and then to employ this understanding toward improved drugs, vaccines and diagnostics. Since Mycobacterium tuberculosis senses and adapts to a wide array of conditions during the disease process, it is clear that the regulation of expression of virulence factors plays an important role in pathogenesis. As a result, a theme of our research is to assess mycobacterial genes important in gene regulation. We are also interested in cell division in mycobacteria and the pathogenesis of caseation and cavitation.

Research Summary

Dr. Bishai is interested in the molecular pathogenesis of tuberculosis. Since Mycobacterium tuberculosis senses and adapts to a wide array of conditions during the disease process, it is clear that the regulation of expression of virulence factors plays an important role in pathogenesis. Hence, a theme of his research has been to assess mycobacterial genes important in gene regulation.

Other active interests are cell division in mycobacteria and the pathogenesis of caseation and cavitation. The use of the mouse and rabbit models of tuberculosis has been a prominent aspect of these studies. Goals of the research program are first to better understand tuberculosis pathogenesis, and then to employ this understanding toward improved drugs, vaccines and diagnostics.

Selected Publications

• Cohen KA, Abeel T, Manson McGuire A, Desjardins CA, Munsamy V, Shea TP3, Walker BJ, Bantubani N, Almeida DV, Alvarado L, Chapman SB, Mvelase NR, Duffy EY, Fitzgerald MG, Govender P, Gujja S, Hamilton S, Howarth C, Larimer JD, Maharaj K, Pearson MD, Priest ME, Zeng Q, Padayatchi N, Grosset J, Young SK, Wortman J, Mlisana KP, O'Donnell MR, Birren BW, Bishai WR, Pym AS, Earl AM. “Evolution of extensively drug-resistant tuberculosis over four decades: whole genome sequencing and dating analysis of mycobacterium tuberculosis isolates from KwaZulu-Natal.” PLoS Med. 2015 Sep 29;12(9):e1001880. doi: 10.1371/journal.pmed.1001880. eCollection 2015.

• Maiga M, Ahidjo BA, Miaga MC, Cheung L, Pelly S, Lun S, Bougoudogo F, Bishai WR. “Efficacy of adjunctive tofacitinib therapy in mouse models of tuberculosis.” EBioMedicine. 2015;2(8):868-873.

• Maiga MC, Ahidjo BA, Maiga M, Bishai WR. “Roflumilast, a Type 4 phosphodiesterase inhibitor, shows promising adjunctive, host-directed therapeutic activity in a mouse model of tuberculosis.” Antimicrob Agents Chemother. 2015;59(12):7888-7890.

• Silva JR, Bishai WR, Govender T, Lamichhane G, Maguire GE, Kruger HG, Lameira J, Alves CN. “Targeting the cell wall of Mycobacterium tuberculosis: a molecular modeling investigation of the interaction of imipenem and meropenem with L,D-transpeptidase 2.” J Biomol Struct Dyn. 2016 Feb;34(2):304-17. doi: 10.1080/07391102.2015.1029000. Epub 2015 Jul 24.

• Srikrishna G, Gupta S, Dooley KE, Bishai WR. “Can the addition of verapamil to bedaquiline-containing regimens improve tuberculosis treatment outcomes? A novel approach to optimizing TB treatment.” Future Microbiol. 2015;10(8):1257-60. doi: 10.2217/FMB.15.56. Epub 2015 Jul 30.

• Winglee K, Lun S, Pieroni M, Kozikowski A, Bishai W. “Mutation of Rv2887, a marR-like gene, confers Mycobacterium tuberculosis resistance to an imidazopyridine-based agent.” Antimicrob Agents Chemother. 2015 Nov;59(11):6873-81. doi: 10.1128/AAC.01341-15. Epub 2015 Aug 24.