Skip Navigation

Jyothi Rengarajan

Email: jrengar@emory.edu

Research Interests

We are interested in understanding how Mycobacterium tuberculosis evades host immunity and how the immune response is regulated during latent and active TB in mouse models and humans. Tuberculosis (TB) provides an excellent system to dissect the molecular basis of infection due to the dynamic interactions between M. tuberculosis and immune cells. M. tuberculosis is one of the world’s most successful human pathogens and is responsible for the deaths of over 1.4 million people annually. The AIDS pandemic and multi and extensively drug-resistant TB further underscore the global public health challenge that TB presents. Developing vaccines and better therapeutics for TB is thus an important goal in our research efforts.

The major questions that we seek to address are: How does M. tuberculosis survive in the host? Why does the host fail to eliminate M. tuberculosis? What kind of vaccine would prevent infection and provide protective immunity? A fundamental aspect of TB that encompasses these questions involves the M. tuberculosis-macrophage interface. Macrophages are central to host defense against microbes, but M. tuberculosis has evolved to evade their anti-microbial functions. We have used functional genomics to comprehensively determine the genome-wide requirements for M. tuberculosis survival and adaptation in host macrophages and in vivo in mice. Using M. tuberculosis mutants that are defective for intracellular growth, we are characterizing (1) the molecular mechanisms used by M. tuberculosis to evade and modulate innate immunity, (2) the host signaling pathways induced in macrophages and dendritic cells upon infection and (3) the effect of these early events on the development of adaptive immunity to infection in vivo. Through these studies, we hope to provide insights into how M. tuberculosis manipulates innate immune function at the molecular level and identify targets for immunomodulatory therapies.

We are also interested in how humans mount immune responses to M. tuberculosis infection. Through clinical collaborations with Dr. Susan Ray at Grady Memorial Hospital and the Fulton County Health Department in Atlanta, our studies aim to understand the immunological basis for TB latency in humans and the development of M. tuberculosis-specific memory T cell responses in patients with active TB who are undergoing anti-tuberculosis chemotherapy. Human immunology studies are important for identifying (1) diagnostic biomarkers for latent and active TB, (2) surrogate markers for monitoring treatment responses in patients and (3) correlates of protective immunity to TB, which is critical for vaccine development.

We are interested in understanding how pathogens evade host immunity and how the immune response combats pathogens. Mycobacterium tuberculosis is one of the world's most successful human pathogens and is responsible for the deaths of up to 3 million people annually. The AIDS pandemic and Multi-drug resistant TB, further underscore the global public health challenge that TB presents. Developing vaccines and better therapeutics for TB is thus an important goal in our research efforts.

The major questions that we seek to address in the lab are: How does M. tuberculosis survive in the host? Why does the host fail to eliminate M. tuberculosis? A fundamental concept that encompasses both these questions involves the M. tuberculosis-macrophage interface. Macrophages are central to host defense against microbes, but M. tuberculosis has evolved to evade their anti-microbial functions. We have used functional genomics to comprehensively determine the genome-wide requirements for M. tuberculosis survival and adaptation in macrophages by identifying mutants with defective intracellular growth. These studies also highlighted genes that are critical for pathogen survival and adaptation to the host, for example, a cell envelope-associated protease that modulates host innate immune responses. We are investigating the molecular and biochemical basis for protease function and have identified potential substrates using mass spectrometry-based proteomics approaches.

Other projects in the lab are focused on dissecting the molecular pathways involved in the host innate immune response to infection in macrophages and dendritic cells. We also have ongoing interests in understanding mechanisms of drug resistance in mycobacteria and identifying targets for new chemotherapeutics. In the long term, we are interested in translating lab-based findings to human population-based settings of tuberculosis infection. Human studies are important for understanding mechanisms underlying host susceptibility, latent infection and protective immunity.

Publications

Research Topics