Research

My research characterizes the evolution and dynamics of interactions between emerging contaminants – such as antibiotics or pharmaceuticals – and organisms in microbial communities. These interactions encompass modification (e.g. xenobiotic detoxification, antibiotic resistance), degradation (e.g. catabolism, mineralization), and community restructuring (e.g. dysbiosis)

I focus on three lines of work that utilize parallel approaches to directly study novel interactions between small molecules and organisms in microbial communities: Mechanism and evolution of antimicrobial modification and degradation, Gut microbiota-mediated modification of pharmaceuticals and metabolites, Microbial community responses to emerging contaminants. I approach these lines of work from complementary angles and at multiple levels of scrutiny (i.e. spanning metagenomics to biochemistry). By studying these functions in isolation and in their native context it is possible to gain greater insight into their evolutionary origins and biochemical niche, as well as to access the great genetic diversity found in microbiomes.

Description

Most clinically-relevant antimicrobials are natural products of soil-dwelling bacteria. The soil harbors diverse microbes which can resist or degrade antibiotics and, in some cases, even catabolize them. While resistance genes are known to be ancient and widely-distributed in the soil, and have been deeply mechanistically characterized, there is a dearth of equivalent knowledge and characterization of mechanisms of antibiotic catabolism. Given its linkage to resistance, understanding the mechanisms of antibiotic catabolism is a pressing concern. Discovery and characterization of these mechanisms and their evolvution and regulation can teach us about the ecology of antibiotics in the environment. Elucidation of antibiotic catabolism pathways may allow for bioremediation of antibiotic-contaminated soils and discovery of antibiotic-remodeling enzymes with utility to industry.

Publications
Press
Description

In my current position as Research Assistant Professor, working alongside the Kelleher research group, I am pursuing projects that leverage my experience using metagenomics and functional screens to identify and characterize promising biosynthetic gene clusters from microbial communities, including those found in the soil and in the large intestines of animals. In the past I studied the bacterial biosynthesis of cobamides, co-enzymes structurally related to vitamin B12 that are among the largest and most complex non-polymeric small molecules known. Generally bacteria only produce one cobamide likely due in part to single enzymatic step in biosynthesis that largely determines what form of cobamide is produced. One possible reason for limiting cobamide diversity is that their ability to act as co-enzymes in particular reactions is altered by their structure.

Publications
Description

Recent studies have identified the large intestinal microbial community as an important actor in host processing of pharmaceuticals and dietary molecules. This includes the large intestine as a site of medically relevant drug transformations, the interaction of the gut microbiome and host immune system as an important factor in certain cancer treatments, and the gut microbiome as an "organ" vulnerable to damage and dysregulation due to antibiotic treatment. Identification of the microbial taxa responsible for these outcomes, and the corresponding enzymes and mechanisms, could be useful in the identification of individuals with increased risk, allowing for personalized treatment options across multiple arenas of medicine.

Publications​