William R. Jacobs Jr. PhD
Professor, Department of Microbiology & Immunology
Professor, Department of Genetics
Investigator, Howard Hughes Medical Institute
Leo and Julia Forchheimer Chair in Microbiology & Immunology
william.jacobs [at] einstein.yu.edu
William R. Jacobs Jr. Ph.D., an HHMI investigator, 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 HHMI 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.
Research Assistant Professor
michael.berney [at] einstein.yu.edu
The overall goal of my research is directed towards understanding how intracellular pathogenic microorganisms metabolize in host tissues. The model for these studies is Mycobacterium tuberculosis. Important questions in my research focus on: (i) Determining the substrates use by Mycobacterium tuberculosis during slow growth and non-replicating persistence in host tissues. (ii) Elucidation of the metabolic and signaling pathways required for slow growth ofM. tuberculosis and metabolism under hypoxia. My research approach is strongly based on bacterial physiology and molecular microbiology. I am using a continuous culture system combined with transcriptomics and metabolomics to study mycobacterial metabolism.
catherine.vilcheze [at] einstein.yu.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.
Research Associate Professor
linda.berney-meyer [at] einstein.yu.edu
MD (Internal Medicine/Nephrology) with interest in immunology, infectious disease and kidney disease.
Currently working on the gene knockout project of Mycobacterium tuberculosis to understand the mechanisms of virulence.
paras.jain [at] einstein.yu.edu
Genetic tools are the integral part of research and are required to revolutionize the study of an organism. I am involved in the development of new tools to ease mycobacterial research, including the development of a mycobacterial expression system, generation of precise deletion mutants by high throughput specialized transduction and to efficiently excise the drug resistance marker (unmarking) from the deletion-substitution mutants. I am also involved in the development of a rapid, sensitive and inexpensive TB detection/drug susceptibility test to be used in poor resource settings. We are at a junction of taking this test from bench to field testing.
brian.weinrick [at] einstein.yu.edu
I am interested in environmentally-dependent regulation of bacterial gene expression and survival mechanisms of tuberculosis bacilli. I am specifically focused on the problem of persistence, the ability of small populations of tuberculosis bacilli to survive antibiotic treatment despite lacking alleles that code for genotypic drug resistance. The phenomenon of persistence may be the basis of the need for lengthy treatment regimens to cure tuberculosis and could also contribute the ability of the bacteria to establish a latent infection. I have characterized the transcriptome of tuberculosis persister cells to identify genes that may be involved in the phenomenon, and have created mutant strains defective for persistence. I am in the process of characterizing these mutants using mouse models and various -omics technologies and work collaboratively on other projects which require systems biological approaches.
Research Specialist I
mayami.sengupta [at] einstein.yu.edu
Herpes simplex viruses are categorized into two types: herpes type 1 and herpes type 2. Both types infect the body’s mucosal surfaces, usually the mouth or genitals, and then establish latency in the nervous system. For both types, at least two-thirds of infected individuals have mild to no symptoms. By comparison, HSV-2 is widely believed to be a painful and dangerous infection. It is the most common cause of neonatal herpes and there is no cure. Genital HSV-2 associated with 2- to 5- fold increase in HIV-1 acquisition which in turn, costs a lot to treat. Therefore, my research focuses on developing a HSV-HIV vaccine.
lina.kaminski [at] einstein.yu,edu |
Persistence in Mycobacterium tuberculosis is a phenomenon of cells where a fraction is resistant to a killing assault as a consequence of a transient gene expression or protein modifications. While several genes were previously proposed as contributing to the emergence of persistence, the complete regulatory network is still unknown and it is clearly not attributed to one ‘persister gene’. My goal is to define the genetic network causing the persistence phenotype in Mycobacterium tuberculosis. I plan to tackle this problem by exploring the roles of the transcription initiation sigma factors in persistence in the presence of bactericidal drugs. This will be done by combining precise null deletions of the sigma factor encoding genes, along with in vitro high throughput screens and in vivo experiments.
tracy.keiser [at] einstein.yu.edu
Mycobacterium tuberculosis has been the most successful pathogen in human history and remains a considerable threat. In part, this is due to a compositionally unique cell wall structure laden with lipids, sugars and lipoglycans. My goal in the lab is to provide a better understanding of the cell wall and to use this knowledge to uncover new drug targets to combat the increasing rate of drug resistant bacteria. To better understand the interaction between the bacterial cell wall and the preferred host cell niche, the human macrophage, I will be using targeted gene deletions in human induced pluripotent stem cells.
adel.malek [at] einstein.yu.edu
The genome of Mycobacterium tuberculosis, an obligate pathogen, encodes 171 distinct transport systems conferring the potential to import and export a diverse array of biomolecules and compounds, only a which have been characterized. My work focuses on characterizing M. tuberculosis transporters critical for nutrient acquisition in vivo and its long-term persistence. I am also interested in mechanisms underlying regulation of these transporters at the level of both expression and activity. I am also working towards creating targeted M. tuberculosis mutants for generating vaccine backbones aimed against tuberculosis and other diseases.
sangeeta.tiwari [at] einstein.yu.edu
Tuberculosis is a dreadful disease. Success of M.tb lies in its survival in macrophages by evasion of host immune responses. Only available vaccine till now is BCG, and its efficacy varies with age and geographical distribution. Therefore, my overall goal is to develop better understanding of the host-pathogen interactions and utilize that to identify potential new drug targets or vaccine candidates. My focus is (1) Identification of novel mycobacterial factors involved in virulence and evasion of host immune responses (2) Understanding of metabolic pathways required for survival and persistence of mycobacteria in the host. I am using multiple techniques involving combination of molecular biology, biochemistry, genetics, metabolomics, cell biology and Immunology to answer these queries.
kayla.weiss [at] einstein.yu.edu
Pathogens have developed an arsenal of strategies to evade host immunity. My research interests lie in defining the mechanisms that either Mycobacterium tuberculosis or herpes simplex virus employ to circumvent detection and elimination by the host immune response. Additionally, I wish to define the immune components that provide the host with the best protection against these pathogens. By delineating both immune evasion strategies and the optimal immune response following either M.tb or HSV infection, I envision vaccines and therapeutic approaches can be developed to permit pathogen sterilization in the host.
christopher.kerantzas [at] med.einstein.yu.edu
I am a fifth year MD/Ph.D. student and I have worked on projects ranging across use of auxotrophic mutants as a replacement for antibiotic resistance cassettes for selection in genetic screens, optimization of mycobacterial recombination, and use of fluorophage for detection of Mycobacterium leprae in clinical samples. My main focus is now on trafficking of iron and the mycobacterial siderophore mycobactin. While synthesis and secretion of mycobactin have been characterized, aspects of uptake still remain ambiguous. Moreover, mutations in the mycobactin synthesis machinery have the potential to generate strains that are effective as new vaccines. I am using various genetic techniques, as well as mass spectrometry to create and characterize mutants involved in these pathways
oren.mayer [at] phd.einstein.yu.edu
My goal in lab is to wage biological warfare on the bacteria that causes tuberculosis. Using phages (viruses that infect bacteria), I’m attempting to develop a therapy to be used either with or instead of antibiotics to kill Mtb in patients Both on the microbiological and genetic level, changes can be made to the phages to make them even better weapons against Mtb. My current work focuses on finding marks for phage resistance in the bacteria so I can make the best choices for a phage cocktail that patients can either breath in or be injected with. In addition, using directed evolution, I am hoping to turn these phages into even more efficient Mtb killing machines.
christopher.petro [at] phd.einstein.yu.edu
Herpes simplex virus (HSV) is a major global health concern. Previous vaccines directed towards HSV-2 have all failed. My thesis project involves characterizing protective immunity towards this pathogen.
Specifically I am looking at systemic and mucosal antibody responses that are protective against primary HSV infection. I am utilizing a genetically modified herpes virus that lacks glycoprotein D as novel HSV vaccine that induces strong protective humoral immunity and understanding the mechanism of protection from these antibodies.
Director of BSL-3 Lab
bing.chen [at] einstein.yu.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 HHMI 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 [at] einstein.yu.edu |
I work on animal experiment, providing technical support for PhD students, post-docs and other lab staff in BSL3 lab. And also I carry out some maintain supplies in BSL3 facility.
laura.cole [at] einstein.yu.edu
I am using a targeted gene deletion technique to generate novel strains of Mycobacterium tuberculosis with individual gene deletions to contribute to the construction of our comprehensive gene knockout library.
I am also developing novel strains of M. tuberculosis to be tested as potential vaccine candidates, and assisting with the assays to characterize their growth, virulence, and immunogenicity.
annie.dai [at] einstein.yu.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.
torin.weisbrod [at] einstein.yu.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