Laboratory of Dr. William R. Jacobs Jr.

The Jacobs Laboratory is located at Albert Einstein of College Medicine. It is the home of exciting research on the "death defying" pathogen, Mycobacterium tuberculosis.

image from the cover of Journal of Infectious Diseases, July 2013

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Laboratory of Dr. William R. Jacobs Jr.

The Jacobs Laboratory is located at Albert Einstein of College Medicine. It is the home of exciting research on the "death defying" pathogen, Mycobacterium tuberculosis.

image from the cover of Journal of Infectious Diseases, July 2013

Our Focus

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.

Vaccine Development

TB Diagnostics

Mycobacterial Genetics

Drug Discovery

Presidential Lecture

Dr. Jacobs Presents at The Second Annual Einstein-Montefiore Presidential Lecture

Pursuing Edward Jenner’s Revenge with Recombinant Herpes Vaccine Vectors

William R. Jacobs, Jr., Ph.D., delivered his lecture, “Pursuing Edward Jenner’s Revenge with Recombinant Herpes Vaccine Vectors” at the second annual Einstein-Montefiore Presidential Lecture. The event was held at Albert Einstein College of Medicine. Dr. Jacobs is a professor of microbiology and immunology at Albert Einstein College of Medicine and a member of the National Academy of Sciences. Watch full event: https://youtu.be/S8yLM7B2Dy0

William R. Jacobs Jr.

Biography

william.jacobs@einsteinmed.org | curriculum vitae | Albert Einstein College of Medicine

William R. Jacobs Jr. Ph.D., a Member of the National Academy of Sciences and Professor of Microbiology and Immunology and Genetics at the Albert Einstein College of Medicine, has dedicated his life to the study of Mycobacterium tuberculosis and M. leprae¸ the causative agents of tuberculosis (TB) and leprosy, respectively. Using a novel mycobacteriophage vector, termed a shuttle phasmid, he was the first to introduce foreign DNA into mycobacteria in 1987. Shuttle phasmids enabled the development of: 1) the first mycobacterial plasmid transformation system, 2) the efficient transposon mutagenesis, and 3) specialized transduction-an efficient allelic system that enables the generation of a complete set of precise null deletions of M. tuberculosis. Moreover, shuttle phasmids enabled the development of reporter mycobacteria phages to rapidly assess drug susceptibilities of M. tuberculosis strains. The Jacobs’ lab used newly developed genetics to identify the previously unknown target of isoniazid-the cornerstone of TB treatment, analyzed the primary attenuation of the vaccine strain BCG, and engineered M. tuberculosis-based TB vaccine strains.

Dr. Jacobs is also one of two leading investigators engaged in the KwaZulu-Natal Research Institute for Tuberculosis and HIV, a partnership aimed at controlling the dual epidemic of HIV/TB that is particularly prevalent in sub-Saharan Africa. He is currently developing rapid diagnostic tests for XDR and MDR-TB using GFP- reporter phages. His work has shifted to focus on persistence in MTB- one aspect that can be considered the greatest impediment to the eradication of TB infection.

“There is no sin in being ignorant; The sin is to remain ignorant”

— Roy Curtiss III, Ph.D

Features

X-Vax Technology Raises $56 Million in Upsized Series A Financing to Advance Lead Herpes Vaccine Program

-A new approach to beating herpes by inducing antibodies that mediate the killing of infected cells

-Participants include Johnson & Johnson Innovation - JJDC, Inc. (JJDC); Adjuvant Capital, an impact investment fund supported by the Bill & Melinda Gates Foundation as an anchor investor; Serum Institute of India; Alexandria Venture Investments; Founders Fund

Losing His Sight, a Scientist Sees an End to a Deadly Disease

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.

Bill Jacobs, the TB terminator

The American Association for the Advancement of Science features Dr. William Jacobs, Jr., dubbed the “TB Terminator,” on its “Member Spotlight” blog. The profile highlights Dr. Jacobs’ pioneering use of molecular genetics to control TB, his drive to discover a new vaccine and his work to encourage student interest – from high school to the master’s level – in science.

TUBERCULOSIS TREATMENT AND MYCOBACTERIAL GENETICS WITH BILL JACOBS

Host Julie Wolf interviews Bill Jacobs on ASM's Meet the Microbiologist podcast. He talks about developing mycobacterial genetic tools and using them to discover ways to shorten TB treatment. He also talks about the SEA-PHAGES program that allows high-school students to participate in phage discovery.

Listen

Lab Personnel

Meet the members of the Jacobs Laboratory

Lab Personnel

Meet the members of the Jacobs Laboratory

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

Principal Investigator | william.jacobs@einsteinmed.edu

Stephanie Velasquez, MPA

Administrator | stephanie.velasquez@einsteinmed.edu

Torin Weisbrod, M.S.

Lab Manager | torin.weisbrod@einsteinmed.edu

I have worked with Bill Jacobs for over 20 years, and currently act as the manager of his lab. I oversee and facilitate all the daily research-oriented activities of the Jacobs group. I am also responsible for coordinating the import/export of scientific materials that support our work. I run occasional targeted experiments for Dr. Jacobs. Acquiring and maintaining the supplies and equipment necessary for our studies is another key part of my role.

Regy Lukose, M.S.

Research Technician | regy.lukose@einsteinmed.edu

I have been involved in the research using recombinant BCG expressing antigens of Malaria, Tuberculosis, HIV, Flu, and Plague. I am currently working to develop the Herpes virus as a vaccine candidate and a platform to express various antigens of Tuberculosis and Flu.

Anna De Oliveira, Ph.D.

Associate | anna.deoliveira@einsteinmed.edu

Viral vectors are promising agents used as vehicles for vaccine delivery, such as some of the recently developed COVID-19 and Ebola vaccines. In the Jacob’s lab, the successful generation of an attenuated recombinant HSV-2 has shown great protection against HSV-2 in immunized mice and guinea pigs models of HSV disease. The further optimization of this HSV-2 vaccine and its use as a platform for the development of vaccines against different infectious diseases has been the focus of my work.

Catherine Vilcheze, Ph.D.

Instructor | catherine.vilcheze@einsteinmed.edu

My research area involves the study of the mechanisms of resistance to the first-line antituberculosis drugs such as isoniazid and pyrazinamide, as well as the identification and testing of new inhibitors against M. tuberculosis. We have shown that the main target of isoniazid is the enoyl-ACP reductase InhA, an essential gene of the fatty acid synthase type II system, deciphered the mechanisms of resistance to isoniazid caused by mutations in ndh encoding the NADH dehydrogenase, and identified a novel mechanism of INH and ETH resistance in M. tuberculosis (mutations in the mycothiol biosynthesis pathway). Screening of a commercially available chemical library led to the identification of 2 new compounds that are cidal against drug-susceptible and drug-resistant M. tuberculosis.

Saranathan Rajagopalan, Ph.D.

Research Fellow | saranathan.rajagopalan@einsteinmed.edu

My research interests are human pathogens, their drug resistance mechanisms and pathogenesis. I have been working on developing Next-Generation Sequencing diagnostics pipeline for human pathogens to provide results in a time frame that would impact patient care. Additionally, I work on a project to make a point of care drug susceptibility test for Mycobacterium tuberculosis and other human pathogens using next-generation luciferase reporter phages.

Lahari Das, Ph.D.

Research Fellow | lahari.das@einsteinmed.edu

I am working on M. tuberculosis and M. leprae. I am involved in the TB vaccine project. Using mycobacteriophages as a tool I am generating Mtb knockout strains for cutinases in order to study their importance in Mtb pathobiology. I am working towards genetically engineering M. leprae to make it grow on synthetic media which will help in developing and screening of novel drug candidates.

Bing Chen, M.D., M.S.

Director of BSL-3 Lab | bing.chen@einsteinmed.edu

I focus on new TB vaccine research and novel anti-tuberculosis agent development, use of animal models to investigate infections and pathogen-host interactions. I am responsible for the safe use of our Bio-Safety Level 3 facility at Einstein, including training and testing post-docs and students according to their own research projects. I also chair the regular meetings of the TB Research Group internal Biosafety Committee for TB research projects and coordinate protocols and resources for BSL3 experiments.”

Mei Chen, B.A.

Research Technician | mei.chen@einsteinmed.edu

My main responsibility is technical support for TB study using animal models in BSL3 facility. I perform IV, SQ, IP, aerosol infection of mouse; harvest and process organ/tissue/blood samples; provide gavage treatment. I also maintain transgenic/knockout mouse colonies. I help with bacterial phage work as well.

John Kim, B.A.

Research Technician | john.kim@einsteinmed.edu

My primary responsibilities as a Research/Animal Technician is to assist students and post-docs with their invivo experimentations. The duties require me to be fairly proficient with numerous animal experimentation techniques, such as retro-orbital bleeding and oral gavage feeding. I also monitor the mice after experimentation noting any phenotypical reactions. In my spare time, I do an inventory check of our supplies in the BSL3 and request reordering of supplies and equipment as needed. Filling out the rest of my time, I am willing to perform any related work duties as needed.

Annie Dai, B.S., R.N.

Research Technician | annie.dai@einsteinmed.edu

I’m a technician in the lab, providing technical support for PhD students, post-docs, and other lab staff. I mainly work on molecular cloning, phage packaging and high-titer phage preparation for specific gene deletions. Also, I carry out some routine laboratory tasks such as preparing specific agar plates which are commonly and largely used in the lab.

Herpes Vaccine

Herpes simplex virus infections remain a serious global health problem and are the leading cause of genital ulcer disease, a major co-factor in the HIV epidemic, and associated with significant morbidity and mortality in newborns born to mothers who are infected. In a recent publication in eLife, Drs. William Jacobs and Betsy Herold of the Albert Einstein College of Medicine have taken a giant step toward developing a viable herpes vaccine.