William R. Jacobs Jr.
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<p style="margin: 0in 0in 8pt; line-height: normal; mso-margin-top-alt: auto; mso-margin-bottom-alt: auto;"><span style="color: black; font-family: 'Verdana',sans-serif; font-size: 10.5pt; mso-fareast-font-family: 'Times New Roman'; mso-bidi-font-family: 'Times New Roman';">The current research interests of my lab include 1) generating complete sets of precise null barcoded deletion mutants of <em>Mycobacterium</em> <em>tuberculosis</em> to screen for virulence and drug persistence in mouse and non-human primate models, 2) understanding persistence-the capacity of subpopulations of <em>M. tuberculosis</em> to resist killing assaults by bactericidal drugs or immune effectors, 3) use of a novel recombinant herpes vector to make novel influenza, Tuberculosis, Dengue, and EEEV vaccines that specifically elicit antibodies that mediate antibody dependent cell mediated cytotoxicity, and 4) develop new luciferase reporter phage point of care diagnostics.</span></p>
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<li>The Exterminators <a href="https://www.esquire.com/news-politics/a3918/exterminators1207/" target="_blank" rel="noopener">https://www.esquire.com/news-politics/a3918/exterminators1207/</a></li&…;
<li>Presidential Lecture <a href="https://www.youtube.com/watch?v=sBsUUW3UrSw" target="_blank" rel="noopener">https://www.youtube.com/watch?v=sBsUUW3UrSw</a></li>
<li>National Academy of Sciences Profile <a href="http://www.nasonline.org/member-directory/members/20030248.html">http:/…;
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<p class="MsoNormal" style="line-height: 15.6pt;"><span style="font-size: 9.0pt;">Dr. Jacobs is pioneering the use of molecular genetics to control tuberculosis (TB), which kills nearly two million people a year. His research is identifying the genes that make<span> </span><em>Mycobacterium tuberculosis</em><span> </span>(MTB) - the bacteria that causes TB - virulent, identifying new drug targets and engineering weakened strains that can be used as live vaccines. Dr. Jacobs was the first scientist to introduce foreign DNA into MTB, a technique now regularly used by TB investigators around the world.</span></p>
<p class="MsoNormal" style="line-height: 15.6pt;"><span style="font-size: 9.0pt;">Dr. Jacobs recently discovered two new ways of killing the bacteria that cause TB, a finding that could also lead to a therapy to prevent drug-resistant TB strains from developing. He also devised an onsite lab test that not only can quickly diagnose TB but can also distinguish treatable TB strains from those that are drug resistant—a process that ordinarily takes months. Dr. Jacobs is participating in a groundbreaking partnership between HHMI and the University of KwaZulu-Natal (UKZN) in South Africa; the partners are establishing an international research center that will contribute to the worldwide effort to control the TB-HIV co-epidemic and will train a new generation of scientists in Africa.</span></p>
<ol>
<li>Tiwari S, Casey R, Goulding CW, Hingley-Wilson S, Jacobs WR Jr. (2019) Infect and Inject: How Mycobacterium tuberculosis Exploits Its Major Virulence-Associated Type VII Secretion System, ESX-1. Microbiol Spectr. PMID: 31172908</li>
<li>Porcelli, S.S, Jacobs WR Jr. (2019). Eacting Edward Jenner's Revenge: The quest for a new tuberculosis vaccine. Sci Trasl Med. PMID: 31043569</li>
<li>Vilcheze C, Jacobs WR Jr. (2019). The Isonizid Paradigm of Killing, Resistance, and Persistence in Mycobcaterium Tuberculosis. J Mol Biol. PMID: 30797860</li>
<li>O'Donnell MR, Larsen MH, Brown TS, Jain P, Munsamy V, Wolf A, Uccellini L, Karim F, D'Olivera T, Mathema B, Jacobs WR, Pym A. (2019). Early Detection of emergent drug resistant tuberculosis (XDR-TB) by flow cytometry-based phenotyping and whole genome sequencing. Antimicrob Agents Chemother. PMCID: PMC6437479</li>
<li>Shen L., Frencher J., Huang D., Wang W., Yang E., Chen C.Y., Zhang Z., Wang R., Qaqish A., Larsen M.H., Shen H., Porcelli S.A., Jacobs W.R., Jr., Chen Z.W. (2019). Immunization of <span style="color: #333333; text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: 'Open Sans', HelveticaNeue, 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 15px; font-style: normal; font-weight: 400; word-spacing: 0px; float: none; display: inline !important; white-space: normal; orphans: 2; widows: 2; background-color: #ffffff; font-variant-ligatures: normal; font-variant-caps: normal; -webkit-text-stroke-width: 0px; text-decoration-style: initial; text-decoration-color: initial;">Vγ2Vδ2</span> T cells programs sustained effector memory responses that control tuberculosis in nonhuman primates. Proc Natl Acad Sci U.S.A. 116 (13): 6371-6378. PMID: 30850538</li>
<li>Johndrow CT, Goldberg MF, Johnson AJ, Ng TW, Kunnath-Velayudhan S, Lauvau G, Kaplan DH, Gossel GH, Kadolsky UD, Yates AJ, Chan J, Jacobs WR Jr, Porcelli SA. (2018). Suppresion of Th1 Priming by TLR2 Agonists during Cutaneous Immunization is Mediated by Recruited CCR2+ Monocytes. J Immunol. 201(12):3604-3616. PMID: 30455402</li>
<li>Bhatt K, Machado H, Osorio NS, Sousa J, Cardoso F, Magalhaes C, Chen B, Chen M, Kim J, Singh A, Ferreira CM, Castro AG, Torrado E, Jacobs WR Jr, Bhatt A, Saraiva M. (2018). A Nonribosomal Peptide Synthase Gene Driving Virulence in <em>Mycobacterium tuberculosis</em>. mSphere. 3(5). PMCID: PMC6211224</li>
<li>Tiwari S, vanTonder AJ, Vilcheze C, Mendes V, Thomas SE, Malek A, Chen B, Chen M, Kim J, Blundell TL, Parkhill J, Weinrick B, Berney M, Jacobs WR Jr. (2018). Arginine-deprived-induced ozidative damage sterilizes <em>Mycobacterium tuberculosis</em>. PNAS. 115(39):9779-9784. PMCID: PMC6166831</li>
<li>Kennedy SC, Johnson AJ, Bharrham S, Linderstam Arlehamn CS, XU J, Garforth SJ, Chan J, Jacobs WR Jr, Settle A, Almo SC, Porcelli SA. (2018). Identification of Mycobacterial Ribosomal Proteins as Targets for CD4+ T Cells that Enhance Protective Immunity in Tuberculosis. Infection and Immunity. 86(9). PMCID: PMC6105890</li>
<li>Vilcheze C, Copelan J, Keiser, Weisbrod T, Washington J, Jain P, Malek A, Weinrick B, Jacobs WR Jr. (2018). Rational Design of Biosafety Level 2-Approved, Multidrug-Resistant Strains of Mycobacterium tuberculosis through Nutrient Auxothrophy. MBio. 9(3). PMCID: PMC5974470</li>
<li>Harbut MB, Yang B, Liu R, Yano T, Vilcheze 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 <em>Mycobacterium tuberculosis</em> Type II NADH Dehydrogenase Exhibit Antimycobacterial Activity. Angew Chem Int Ed Engl. 57(13):3478-3482. PMCID: PMC6066186</li>
<li>Vilcheze 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. PMCID: PMC5816213</li>
<li>Vilcheze C, Kim J, Jacobs WR Jr. (2018). Vitamin C potentiates the killing of <em>Mycobacterium tuberculosis</em> by the first-line tuberculosis drugs isoniazid and rifampicin in mice. Antimicrob Agents Chemother. PMCID: PMC5826150</li>
<li>Burn, C., Ramsey, N., Garforth, S.J., Almo, S., Jacobs, W.R., Jr. and Herold, B.C. (2018). 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. PMCID: PMC5853290</li>
<li>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. PMCID: PMC5686121</li>
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