Engineering New Platforms for the Study of Infectious Diseases

The Freundlich group is located at Rutgers University in the Department of Pharmacology, Physiology and Neuroscience and the Department of Medicine (Division of Infectious Diseases, Center for Emerging & Re-emerging Pathogens). The Freundlich laboratory is positioned at the intersection of computation, chemistry, and biology to develop new tools that contribute to our understanding of the pathogenesis of infectious diseases (caused by M. tuberculosis, ESKAPE bacteria, P. falciparum, and the Zika virus) and translate these toward the discovery of novel therapeutic strategies. Innovative computational workflows, based on machine learning methods with or without high-throughput target-based virtual screening, are devised to discover new small molecule chemical tools with efficacy versus a specific infectious agent and then evolve the activity, physiochemical, Absorption-Distribution-Metabolism-Excretion-Toxicity, and pharmacokinetic/pharmacodynamic profiles such that in vivo validation is achieved. This validation is relevant to the actual small molecule, potentially enabling its transition to a drug discovery pipeline, as well as its mechanism of action. While medicinal chemistry heuristics are combined with computational methods in the optimization of molecules pertinent to a range of infectious diseases, biological methods in the laboratory contribute to a fundamental understanding of their mechanism of action. Biochemistry, microbiology, and genetics are harnessed to identify the biological target/s of the small molecule. The Freundlich laboratory is a leading proponent of the study of 1) intrabacterial metabolism and 2) polypharmacology of small molecule antibacterials. Interrogation of these interrelated phenomena has led us to a detailed understanding of the underpinnings of antibacterial mechanism of action.

         Thus far, primarily with support from the National Institutes of Health, the Freundlich lab has contributed to the validation of novel antibacterial therapeutic strategies through both novel chemotypes for tool compounds and drug discovery entities and validated drug targets. Efforts are ongoing to translate these basic discoveries toward high impact therapies for bacterial and viral infections.

 

The Freundlich lab, during our group meeting on Halloween, 2016