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Institute for Infectious & Inflammatory Diseases

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Featured Project

Mycobacterium tuberculosis

Joel S. Freundlich, Ph.D.
Associate Professor
  |  Department of Pharmacology and Physiology, Center for Emerging Pathogens

The Freundlich group at Rutgers University is housed in the departments of Pharmacology & Physiology and Medicine and is part of the Center for Emerging Pathogens. Our presence in more than one department and a center reflects the interdisciplinary nature of our research. We seek to deeply probe the infection biology of pathogens of global health relevance through an innovative combination of computation, chemistry, and biology. The laboratory is a training ground for students at these interfaces such that they develop a defined expertise as well as secondary competencies that afford them a unique set of tools to study their respective biological systems. The research produced is designed to elucidate novel insights in pathogen biology to seed new therapeutic strategies, chemical tools, and drug discovery small molecules.

Our predominant focus is Mycobacterium tuberculosis – the causative agent of tuberculosis. Tuberculosis represents a global health pandemic, infecting 8.6 million people and killing 1.3 million people per annum. The dire need for novel therapeutic strategies (biological targets and small molecule drugs) has driven us to contribute to this field. Given the general applicability of the computational and chemical technology platforms we are developing, we also are contributing to programs focused on Plasmodium falciparum (one of the malarial parasites) and ESKAPE pathogens and Select Agents.

A lay overview of our research may be crystallized around the development and application of methods from computation, chemistry, and biology to unravel essential and vulnerable biological pathways within the pathogen. For example, how does the pathogen adapt to life within the infected host and in turn how does the host adapt to the presence of pathogen? Our computational methods seek to leverage >500,000 small molecules that have been assayed for their growth inhibition of M. tuberculosis and the datasets provided by such efforts. This knowledge may be learned from in novel ways to guide future studies. Critically, we have demonstrated that our machine-learning techniques are both time- and cost-efficient and are capable of predicting novel small molecules with significant promise as chemical probes to study pathogen biology and starting points for drug discovery efforts. We probe small molecule perturbation of M. tuberculosis through a wide range of biological techniques (biochemical, microbiological, transcriptional, metabolomic).

The Freundlich laboratory is currently supported by a number of grants from the National Institutes of Health and the Charles and Johanna Busch Memorial Fund, and has also received support in the past from the New Jersey Health Foundation.