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Kevin Pethe

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Education

  • Research Fellow, Cornell University, Ithaca, USA
  • Ph.D., Universite de Lille & Institut Pasteur de Lille, France
  • M.Sc., Universite de Lille, France

Professional Experience

  • Research Investigator, Novartis Institute for Tropical diseases, Singapore
  • Senior Research Investigator, Novartis Institute for Tropical diseases, Singapore
  • Adjunct Assistant Professor, School of Medicine, National University of Singapore
  • Head of tuberculosis and antibacterial drug discovery unit, Institut Pasteur Korea
  • Head of project management, Institut Pasteur Korea
  • Executive director, biology & core technology centers
  • Acting CEO, Institut Pasteur Korea

Major Research Interests

  • Regulation and adaptation of bacterial metabolism
  • Synthetic lethal interactions as antibacterial drug targets
  • System-level perturbation induce by antibiotics

Research Interests

Regulation and adaptation of bacterial metabolism
Bacteria have developed strategies to take advantage of the nutritional resources of their host for growth and persistence. We study how bacteria adapt their metabolism to exploit host metabolites (and how the host restricts access to those metabolites), a process that is crucial if we are to understand pathogenesis, and by extension commensality. The competition for resources between pathogenic and commensal bacteria at the mucosal surface is a related interest of the lab.

Synthetic lethal interactions as antibacterial drug targets
Synthetic lethality is a powerful therapeutic concept. It arises when mutations in two or more genes, which when singly mutated have no effect on viability, together cause the death of a cell or organism. We are characterising metabolic synthetic lethal genetic interactions in bacteria. Several lines of evidence suggest that a combination of weakly active chemical entities can result in a potent synergistic drug combination against multidrug resistant bacteria, revealing the existence of numerous synthetic-lethal genetic interactions. In order to develop novel antibacterial drug combinations, we use a genetic and chemical genomics approach to decipher how a slight perturbation of multiple metabolic pathways can lead to a collapse of an entire biological system.

System-level perturbation induce by antibiotics
A third interest of the lab is to study the systems-level perturbation induced by antibiotics; recent findings suggest that antibiotic-induced cell death is not directly linked to the inhibition of the primary target but to a collapse of central metabolism. We thus seek to elucidate the mechanisms by which antibacterials induce cell-death, using a multidisciplinary approach combining functional genomics, chemical biology, genetics and biochemistry.