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

Sterilizing Chemotherapies and Immunotherapies against Tuberculosis, Herpes, and Influenza

 

Tuberculosis:

Tuberculosis (TB) remains the single leading infectious disease in the world, causing over 10 million new cases per year and accounting for 1.6 million deaths annually. The onset of the HIV epidemic worsened the TB global health burden leading to increases in incidences, reactivated disease, and the emergence of drug resistance. The worsening problem of TB is surprising because both a vaccine and sterilizing chemotherapy exist to treat this disease. A major reason for the ineffectiveness of these therapies, is TB’s ability to persist; persistence is the capacity of Mycobacterium tuberculosis (Mtb) to survive sterilization in animals and humans. Persistence is also an epigenetic process found in all bacteria and cancer cells.  Recently, we demonstrated populations of Mtb have a subpopulation of Mtb cells that are phenotypically resistant to bactericidal antibiotics. We have identified specific transcriptional patterns that regulate phenotypic resistance and developed dual reporter mycobacteriophages to rapidly identify this subpopulation of cells. Moreover, we discovered the addition N-acetylcysteine or Vitamin C to cultures of Mtb prevent the formation of persisters and allow for rapid sterilization in the presence of bactericidal drugs. Current efforts are focused on characterizing the mechanisms by which persisters are formed and identifying relevant targets to eliminate these persisters.

 

Herpes and Influenza:

In collaboration with Dr. Betsy Herold, we have generated a precise deletion of the gene encoding gD of Herpes Simplex Virus (HSV) 2, termed ΔgD-2, that upon immunization in mice elicits sterilizing immunity against challenge with HSV-1 and HSV-2. This unprecedented protection results from the induction of a special type of antibodies that mediate antibody dependent cell mediated killing (ADCK) of herpes infected cells. We have subsequently found that many pathogens do not elicit ADCK antibodies but we hypothesized that by cloning genes encoding important antigens into our herpes viral vector, we could elicit protection against other pathogens such as influenza. Recently, our lab generated recombinant ΔgD-2 herpes virus expressing genes encoding flu antigens and demonstrated that we can confer complete protection against the homologous influenza challenge. This proof of principle suggests that by cloning antigens from other pathogens, such as Mtb, it is possible to make novel vaccines and elicit ADCK antibodies. Thus other efforts in Jacobs lab focus on characterizing the mechanisms by which the ADCK antibodies facilitate the collaboration of innate immunity with adaptive immune responses.

TB TERMINATOR

THE EXTERMINATORS

 

Selected Publications

  1. Tiwari S, vanTonder 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. (2018). “Arginine-deprived-induced ozidative damage sterilizes Mycobacterium tuberculosis.” PNAS. 115(39):9779-9784. PMCID: PMC6166831
  2. 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. PMCID:  PMC5410800
  3. Jain P, Weinrick BC, Kalivoda EJ, Yang H, Munsamy V, Vilcheze C, Weisbrod TR, Larsen MH, O’Donnell MR, Pym A, Jacobs WR Jr. (2016). Dual-Reporter Mycobacteriophages (Φ2DRMs) Reveal Preexisting Mycobacterium tuberculosis Persistent Cells in Human Sputum.” MBio. (5). pii: e01023-16. PMCID: PMC5080378
  4. Petro, C., González, P.A., Cheshenko, N., Jandl, T., Khajjoueinejad, N., Bénard, A., Sengupta, M., Herold, B.C., Jacobs, W.R., Jr. (2015)  Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease. eLife.  PMCID PMC4352706

 

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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 577
Bronx, NY 10461

Tel: 718.678.1075
Fax: 718.678.1085

Research Information

In the News

The Scientist quotes Dr. William Jacobs Jr. on the development of tuberculosis infections in humans on immune-boosting cancer treatments.

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

More media coverage