Faculty Profile

Dr. William R. Jacobs, Jr., Ph.D.

William R. Jacobs, Jr., Ph.D.

Professor, Department of Microbiology & Immunology

Professor, Department of Genetics

Leo and Julia Forchheimer Chair in Microbiology & Immunology

Areas of Research: Mycobacterium tuberculosis genetics; mycobacteriophages; extensively drug resistant tuberculosis (XDR-TB); tuberculosis vaccines; mechanism of isoniazid action. Herpes simplex and Influenza vaccine development

Professional Interests

Extensively Drug Resistant Mycobacterium tuberculosis: The Death Defying Pathogen

Tuberculosis, caused by Mycobacterium tuberculosis, causes one in four avoidable deaths in the Third World and kills more adults than malaria, AIDS, and all tropical diseases combined. In recent years, there have been dramatic increases in the numbers of new cases worldwide - one of the consequences of the AIDS epidemic. In addition to these increasing incidences, there has been an emergence of M. tuberculosis strains that are resistant to all seven anti-tuberculosis agents. These alarming trends have caused the World Health Organization to declare tuberculosis a global health emergency, a distinction never accorded another disease. My laboratory has focused its efforts on developing systems to genetically manipulate mycobacteria, particularly M. tuberculosis. These tools have allowed us to: 1) develop the luciferase reporter phage assay for rapid assessment of drug susceptibilities, 2) analyze the genes involved in resistance to tuberculosis drugs such as isoniazid, ethionamide, and etyhambutol, and 3) to identify specific phenotypic properties associated with a tuberculosis pathogenesis. Current research efforts are aimed at identifying genes involved in the virulence of M. tuberculosis, identifying novel drug targets, generating rapid and robust phage diagnostics for drug resistant strains of M. tuberculosis, and engineering attenuated mutants of M. tuberculosis and other mycobacteria that can be used as live-cell tuberculosis vaccines.

 

TB TERMINATOR

 

THE EXTERMINATORS

 

Selected Publications

1. Tiwari S, van Tonder AJ, Vilchèze C, Mendes V, Thomas SE, Malek A, Chen B, Chen M, Kim J, Blundell TL, Parkhill J, Weinrick B, Berney M, Jacobs WR Jr. Arginine-deprivation-induced oxidative damage sterilizes Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2018 Aug 24. [Epub ahead of print] PMID: 30143580

2. Vilchèze C, Copeland J, Keiser TL, Weisbrod T, Washington J, Jain P, Malek A, Weinrick B, Jacobs WR Jr. Rational Design of Biosafety Level 2-Approved, Multidrug-Resistant Strains of Mycobacterium tuberculosis through Nutrient Auxotrophy. MBio. 2018 May 29;9(3). PubMed PMID: 29844114

3. Harbut MB, Yang B, Liu R, Yano T, Vilchèze C, Cheng B, Lockner J, Guo H, Yu C, Franzblau SG, Petrassi HM, Jacobs WR Jr., Rubin H, Chatterjee AK, Wang F. (2018). “Small Molecules Targeting Mycobacterium tuberculosis Type II NADH Dehydrogenase Exhibit Antimycobacterial Activity.” Angew Chem Int Ed Engl. 57(13):3478-3482. PMID: 29388301

4. Vilchèze C, Weinrick B, Leung LW, Jacobs WR Jr. (2018). “Plasticity of Mycobacterium tuberculosis NADH dehydrogenases and their role in virulence.” PNAS. 115(7):1599-1604. PMID: 29382761

5. Vilchèze C, Kim J, Jacobs WR Jr. (2018). “Vitamin C potentiates the killing of Mycobacterium tuberculosis by the first-line tuberculosis drugs isoniazid and rifampicin in mice.” Antimicrob Agents Chemother. PMID: 29298757

6. Burn, C., Ramsey, N., Garforth, S.J., Almo, S., Jacobs, W.R., Jr. and Herold, B.C. (2017). "An HSV-2 single-cycle candidate vaccine deleted in glycoprotein D, DeltagD-2, protects male mice from lethal skin challenge with clinical isolates of HSV-1 and HSV-2". J Infect Dis. PMID: 29216362.

7. Hanauer, D.I., Graham, M.J., Betancur, L., Bobrownicki, A., Cresawn, S.G., Garlena, R.A., Jacobs-Sera, D., Kaufmann, N., Pope, W.H., Russell, D.A., Jacobs, W.R., Jr., Sivanathan, V., Asai, D.J. and Hatfull, G.F. (2017). "An inclusive Research Education Community (iREC): Impact of the SEA-PHAGES program on research outcomes and student learning". Proc Natl Acad Sci U S A. PMID: 2920871

8. Retamal-Diaz, A., Weiss, K.A., Tognarelli, E.I., Freire, M., Bueno, S.M., Herold, B.C., Jacobs, W.R., Jr. and Gonzalez, P.A. (2017). "US6 Gene Deletion in Herpes Simplex Virus Type 2 Enhances Dendritic Cell Function and T Cell Activation". Front Immunol. (8)1523. PMID: 5686121

9. Stratton, T.P., Perryman, A.L., Vilcheze, C., Russo, R., Li, S.G., Patel, J.S., Singleton, E., Ekins, S., Connell, N., Jacobs, W.R., Jr. and Freundlich, J.S. (2017). "Addressing the Metabolic Stability of Antituberculars through Machine Learning". ACS Med Chem Lett. 8(10):1099-1104. PMID: 29057058

10. Kunnath-Velayudhan, S., Goldberg, M.F., Saini, N.K., Johndrow, C.T., Ng, T.W., Johnson, A.J., Xu, J., Chan, J., Jacobs, W.R., Jr. and Porcelli, S.A. (2017). "Transcriptome Analysis of Mycobacteria-Specific CD4+ T Cells Identified by Activation-Induced Expression of CD154". J Immunol. 199(7):2596-2606. PMID: 28821584

11. Liu, R., Lyu, X., Batt, S.M., Hsu, M.H., Harbut, M.B., Vilcheze, C., Cheng, B., Ajayi, K., Yang, B., Yang, Y., Guo, H., Lin, C., Gan, F., Wang, C., Franzblau, S.G., Jacobs, W.R., Jr., Besra, G.S., Johnson, E.F., Petrassi, M., Chatterjee, A.K., Futterer, K. and Wang, F. (2017). "Determinants of the Inhibition of DprE1 and CYP2C9 by Antitubercular Thiophenes". Angew Chem Int Ed Engl. PMID: 28815830

12. Glass, L.N., Swapna, G., Chavadi, S.S., Tufariello, J.M., Mi, K., Drumm, J.E., Lam, T.T., Zhu, G., Zhan, C., Vilcheze, C., Arcos, J., Chen, Y., Bi, L., Mehta, S., Porcelli, S.A., Almo, S.C., Yeh, S.R., Jacobs, W.R., Jr., Torrelles, J.B. and Chan, J. (2017). "Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth". PLoS Pathog. 13(7):e1006515. PMID: 28753640

13. Yang, Y., Thomas, J., Li, Y., Vilcheze, C., Derbyshire, K.M., Jacobs, W.R., Jr. and Ojha, A.K. (2017). "Defining a temporal order of genetic requirements for development of mycobacterial biofilms". Mol Microbiol. PMID: 28628249

14. Saito, K., Warrier, T., Somersan-Karakaya, S., Kaminski, L., Mi, J., Jiang, X., Park, S., Shigyo, K., Gold, B., Roberts, J., Weber, E., Jacobs, W.R., Jr. and Nathan, C.F. (2017). "Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations". Proc Natl Acad Sci U S A. 114(24):E4832-E4840. PMID: 28559332

15. Qaqish, A., Huang, D., Chen, C.Y., Zhang, Z., Wang, R., Li, S., Yang, E., Lu, Y., Larsen, M.H., Jacobs, W.R., Jr., Qian, L., Frencher, J., Shen, L. and Chen, Z.W. (2017). "Adoptive Transfer of Phosphoantigen-Specific gammadelta T Cell Subset Attenuates Mycobacterium tuberculosis Infection in Nonhuman Primates". J Immunol. 198(12):4753-4763. PMID: 28526681

16. Vilcheze, C., Hartman, T., Weinrick, B., Jain, P., Weisbrod, T.R., Leung, L.W., Freundlich, J.S. and Jacobs, W.R., Jr. (2017). "Enhanced respiration prevents drug tolerance and drug resistance in Mycobacterium tuberculosis". Proc Natl Acad Sci U S A. 114(17):4495-4500. PMID: 28396391

17. Ryan, A., Polycarpou, E., Lack, N.A., Evangelopoulos, D., Sieg, C., Halman, A., Bhakta, S., Eleftheriadou, O., McHugh, T.D., Keany, S., Lowe, E.D., Ballet, R., Abuhammad, A., Jacobs, W.R., Jr., Ciulli, A. and Sim, E. (2017). "Investigation of the mycobacterial enzyme HsaD as a potential novel target for anti-tubercular agents using a fragment-based drug design approach". Br J Pharmacol. 174(14):2209-2224. PMID: 28380256

18. Prados-Rosales, R., Carreno, L., Cheng, T., Blanc, C., Weinrick, B., Malek, A., Lowary, T.L., Baena, A., Joe, M., Bai, Y., Kalscheuer, R., Batista-Gonzalez, A., Saavedra, N.A., Sampedro, L., Tomas, J., Anguita, J., Hung, S.C., Tripathi, A., Xu, J., Glatman-Freedman, A., Jacobs, W.R., Jr., Chan, J., Porcelli, S.A., Achkar, J.M. and Casadevall, A. (2017). "Enhanced control of Mycobacterium tuberculosis extrapulmonary dissemination in mice by an arabinomannan-protein conjugate vaccine". PLoS Pathog. 13(3):e1006250. PMID: 5360349

19. Kerantzas, C.A. and Jacobs, W.R., Jr. (2017). "Origins of Combination Therapy for Tuberculosis: Lessons for Future Antimicrobial Development and Application". MBio. 8(2): PMID: 28292983

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More Information About Dr. William Jacobs, Jr.

Bill Jacobs Lab

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Albert Einstein College of Medicine
Michael F. Price Center
1301 Morris Park Avenue , Room 555
Bronx, NY 10461

Tel: 718.678.1075
Fax: 718.678.1085

Research Information

In the News

Science News interviews Dr. Betsy Herold about her new research with Dr. Bill Jacobs on an experimental herpes vaccine.

In a Nautilus profile, Dr. William Jacobs, Jr., discusses the key breakthroughs in his tuberculosis research and how losing his vision impacted his career path.

More media coverage