Research & Initiatives
The Caesar Research Group focuses on combining analytical chemistry, chemical ecology, and natural products chemistry to discover new compounds from Nature for combatting disease.
Bacteria, Fungi, and Plants are prolific producers of natural products, small molecules that help them secure their ecological niche. Thousands of years of evolutionary selection have turned bacteria, fungi, and plants into expert synthetic chemists capable of biosynthesizing intricate natural products with powerful and specific bioactivities fine-tuned to suit their ecological needs. These natural products have become an invaluable source of inspiration for drug discovery, and nearly two-thirds of pharmaceutical drugs on the market today are directly from or inspired by Nature.
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In the Caesar lab, we leverage the power of mass spectrometry to analyze complex natural products extracts. We aim to understand the ecological role of natural products to gain clues into their biological activities with the ultimate goal of discovering new molecules to combat disease.
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Exploring the Bat Microbiome to Fight White-Nose Syndrome
Infectious diseases affecting wildlife are on the rise, with broad implications for conservation and human public health. White-nose syndrome, caused by the fungus Pseudogymnoascus destructans, has devastated North American bat populations, killing millions since 2007. In 2017, our collaborators issued a report outlining the role of bat microbiomes in protecting their hosts against P. destructans infection, illustrating that susceptible bats lack key organisms in their microbiomes. We hypothesize that resistant bats are afforded protection by antifungal metabolites produced by their bacterial symbionts. To date, our collaborators have isolated >1600 bacteria from the external bat microbiome, 98 of which have inhibitory effects against P. destructans. With this project, we combine metabolomics, genomics, and biological activity testing to determine which metabolites are responsible for this inhibitory activity.
Fungi as an Unexplored Resource for New Medicines
Fungi are hyper-diverse organisms that are found as symbionts or pathogens with higher organisms, and in nearly every environment. In nature, fungi exist in complex environments where they must adapt to constantly fluctuating conditions, and many metabolites are only induced in the presence of the proper environmental stimuli. By maintaining epigenetic control over secondary metabolism, fungi can maximize energy efficiency, only manufacturing secondary metabolites when their presence is likely to provide a competitive advantage. Fungi represent an untapped reservoir of novel natural product molecules, but to truly access the biochemical wealth of fungi, methods to understand and manipulate factors influencing gene expression must be developed. With this project, we are working on cultivating a fungal library for drug discovery at JMU, and plan to develop ecologically-inspired culture conditions to shed light on how chromatin architecture and cell-to-cell communication impact gene expression, providing access to unexplored chemical space and enhancing the likelihood of natural product discovery.
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Uncovering the Complexity of Medicinal Plants
Plants have been used as medicine since the beginning of human history, and ancient texts from Sumeria, Egypt, India, China, and many others containing recipes for medicinal plant preparations have been discovered. In the United States, nearly 20% of adults and 5% of children use botanical supplements as part of their health care regiment, while a significant part of the global population utilizes herbal medicines as their primary form of healthcare. Despite the centuries-long relationship between humans and plant medicines, the activity of botanical medicines is only partly understood, and the plant constituents responsible for biological activity are often unknown. With this project, we seek to identify biologically active constituents (and their potential interactions) from traditionally used botanical medicines.