Professor of Surgery Harvard Medical School

Director, Molecular Surgical Laboratory, Department of Surgery Massachusetts General Hospital

Investigator, Full Prof (M) Surgical Oncology, Mass General Research Institute

MGH Research Scholar 2020-2025 Mass General Research Institute, Massachusetts General Hospital

PhD University of California, Berkeley 1991

M.Sc. University of Naples and National Institute of Genetics and Biophysics, Naples, Italy, 1985

acetophenones; animals; anti-bacterial agents; anti-infective agents; arabidopsis; bacterial biofilms; biomarkers; burn injury; epigenetics; gene expression regulation bacterial; immunity; leaky gut; mitochondria; muscle skeletal; plant diseases; prognosis; pseudomonas; pseudomonas aeruginosa; pseudomonas infections; quorum sensing; small molecules; virulence Hard-to-eradicate, often untreatable, infections including chronic and relapsing infections and infections of medical devices pose increasing threats to human health worldwide. Such infections are often refractory to antibiotics due their resistant to multiple antibiotics and/or antibiotic tolerance of a subpopulation of bacterial cells that are not antibiotic resistant mutants but rather “dormant” cells that survive antibiotic killing. According to the existing paradigm many chronic infections are therefore untreatable.

To achieve our aim, our research is driven towards discovery of critical pathogen and host molecular mechanisms that mediate or restrict bacterial pathogenesis. We employ a multi-disciplinary approach that uses the non-vertebrate and vertebrate infection models we developed to identify and characterize mechanisms that govern host-pathogen antagonistic interactions. The Lab is committed to applying One Health systems biology approach in understanding such mechanisms, through the application of methods drawn from microbiology, molecular biology, genetics, chemistry, biochemistry, immunology and physics, with the ultimate goal of developing novel host-protective and anti-bacterial interventions.

Our novel research bridges the new knowledge gleaned from the basic sciences and the world of clinical medicine to open new avenues for the development and testing of innovative therapeutics for prevention and treatment of severe and untreatable infections. Major Lab projects focus on regulatory systems that govern bacterial virulence and host responses to infection and trauma. Emphasis is given on quorum sensing (QS) and the role of QS regulated small molecules in bacterial virulence in both mono- and polymicrobial settings, and in the inter-kingdom modulation of host responses (immune and metabolic) and host tolerance/resilience to infection. To date, our discoveries have led to the development of highly promising anti-virulence therapeutics and infection risk prognostic biomarkers for the treatment and/or prevention of deleterious infections.