Projects

We live in a 3D world!

We use our chemical cartography approach to understand the spatial context of disease development, by investigating the chemical interplay between mammalian hosts, their environment and microorganisms in 3D.  Using mass spectrometry-based metabolomics, combined with big data statistical tools and three-dimensional modeling, we place molecules in their spatial context and link them to microbial community composition and human health. This approach helps us determine how a given micro-environment influences pathogen tropism, how antimicrobial sensitivity is spatially variable, and how we interact with our environment, with many other exciting possible applications! We then use this information to guide rational drug and vaccine development and changes in health practices, so that our discoveries can be translated into applications that improve human health, with a particular focus on neglected tropical diseases and diseases of poverty.

Current work focuses on:

1. Applying chemical cartography to define the chemical rules of pathogen and disease tropism. Why do diseases happen where they do in the world? Why do pathogens colonize one organ but not another? Why do some organ locations recover from infection and others stay permanently damaged? We use our unique method to address these questions across a range of viral and parasitic disease systems. This work has important implications for how we diagnose and treat disease.

2. Applying chemical cartography and metabolomics to understand microbiome function.  Although the role of the microbiome in health and disease is now well established, the mechanisms by which the microbiome influences health are still not fully understood.  Our 3D perspective helps us understand the changes happening locally at the site of microbial colonization and on a global scale, and then to connect these changes to overall health status.

3. Spatially-resolved exposomics research.  By characterizing the relationship between building surfaces, small molecules, and the human skin, we are beginning to understand how our day-to-day lives put us in constant contact with a variety of chemicals, some of which have the potential to affect our health. This research topic is being developed in the context of investigation-driven graduate courses and hands-on undergraduate research.

4. Translational implementations of chemical cartography. Characterizing chemical interactions between humans, their environment, and microorganisms is only the first step! We use our data to develop new sensitive diagnostic tests to assess disease severity and infection outcome.  We also explore whether modulating local signals affect pathogen tropism and disease progression, in a drug development framework.  Our spatial perspective enables us to redefine the factors controlling phenotypic resistance to antimicrobials, test how drug sensitivity varies within a given organ or tissue, and develop new approaches to clear dormant organisms. Finally, we are also interested in using our data to develop and improve rational immunization strategies for parasitic diseases. We focus on diseases where the clinical need is most acute, including Chagas disease and leishmaniasis. This is achieved in-house through our pre-clinical animal model systems, and via clinical collaborations.