The microbial ecology of the human body
Microbes are nature’s chemists, capable of producing and metabolizing a diverse array of compounds. In the human gut, microbial biochemistry can be beneficial, for example by producing vitamins or breaking down the complex carbohydrates of our diet; or detrimental, such as reactivating an inactive drug metabolite and causing patient toxicity. I will start by describing how we study and think about the human ‘microbiome’, the collective of bacteria, archaea, small eukaryotes, fungi, and viruses that live in our body, and its role in health and disease. I will comment on why it has proven so difficult to treat diseases via microbiome interventions and argue that identifying clinically relevant microbiome metabolism requires linking microbial biochemistry and ecology with patient outcomes. I will end by discussing my lab’s work discovering how microbes metabolize drugs in the guts of human patients and how the vast, uncharacterized collective of viruses of microbes might influence ecosystem function in the human body.
Dr. Kelly started her scientific career working on the Human Genome Project as a bioinformatics specialist at the Stanford Human Genome Center after graduating from Stanford University (BA, Human Biology). She got her PhD in Biomedical Informatics at the University of California, San Francisco, working with Dr. Andrej Sali to predict the impact of single nucleotide variants---the most common form of human variation---on the function of human drug transporters. In collaboration with the lab of Dr. Deanna Kroetz, Dr. Kelly’s work revealed previously unknown conserved structural features associated with human diseases in ABC transporters. As a postdoc at the Massachusetts Institute of Technology, Dr. Kelly shifted her focus to genetic variation in the microbial communities of the global oceans. In the lab of Dr. Sallie Chisholm in the Department of Civil and Environmental Engineering Dr. Kelly’s work revealed an active and dynamic role for viruses as metabolic engineers of bacterial cells in the ocean.
Dr. Kelly’s lab, in the departments of Systems and Computational Biology and Microbiology and Immunology at Albert Einstein College of Medicine in New York, studies the interplay between genetic diversity, ecosystem function, and clinical phenotypes in the microbial communities that inhabit the human body (the ‘microbiome’). The lab focuses on the how microbes metabolize drugs in the guts of human patients and how viruses of microbes might influence ecosystem function in the human body. In part, the lab has 1) shown that individual microbiomes metabolize the anti-cancer drug irinotecan differently, with possible implications for drug toxicity; 2) identified hundreds of potential microbiome/drug interactions computationally and experimentally verified that the ovarian cancer drug altretamine is metabolized by the microbiome; and 3) identified novel viruses in the ocean that also inhabit the human body.