My research interests are focused on small molecule mass spectrometry in vertebrate models to examine 1) changes in chemical signatures during disease states or stress such as ionizing radiation and 2) chemical ecology of host/pathogen interactions. Small molecule signatures can hold a wealth of information representative of an organism’s phenotypic state. Mass spectrometry technologies have evolved to a point where even small tabletop instruments can be used to capture these molecular fingerprints for various applications, including Biomarker Discovery and Emerging Fungal Diseases of Wildlife.
Due to increased terrorist threats and potential nuclear accidents, there is a need for medical countermeasures for radiological exposures. Specifically, clinical and field based diagnostic tools for biodosimetry is required for determination of individual radiation exposure. Metabolomics (analysis of molecules < 1 kDa) is a relatively emergent technology for rapid high throughput analysis of easily accessible biofluids that may assess individual radiation exposure. I utilize UPLC-MS platforms for developing metabolomic and lipidomic radiation signatures from human and nonhuman primate urine and serum, which are easily translatable across animal models for future experiments in physiology. More recently, we have been involved in research to determine how variability in the general population or dose rate may affect dose reconstruction.
For population level variability, we showed that radioresistant phenotypes (p53-/- model) may show attenuated responses post-irradiation but our small-molecule signature remained relatively unaffected. Additionally, dampened autoimmune and inflammatory responses (null alternative p38 pathway model) did not affect dose reconstruction. For dose rate variability, we designed a set of experiments utilizing both low and high-dose rate scenarios using novel irradiation systems with retired 137Cs brachytherapy seeds in a pulley system (~1 Gy/day) or a modified clinical linac (7 Gy/sec) respectively. While we similarly found our multiplex panel could determine total dose delivered irrespective of dose rate, these experiments led to the discovery of a novel compound, hexosamine-valine-isoleucine-OH.
Fungal diseases in wildlife populations have caused massive declines, to the point of regional extinctions, and have become increasingly prolific due to globalization and climate change. White nose syndrome (WNS) is one such disease caused by a psychrophilic fungus, Pseudogymnoascus destructans (or Pd for short), that has devastated North American bat communities for over a decade. Pd causes visible lesions on bat wings and at more severe stages of disease, causes death through starvation and dehydration. I have addressed ow the host integumentary lipidome is affected during fungal infections and how do protective lipids on the skin differ between species. If bats possess different natural mechanisms to deter growth this could determine priority species for conservation. Read. my latest
Also, I described the first serine protease (PdSP1) may function in wing necrosis observed during infection. This study led to the first isolation/description of a protease from P. destructans. More recently, I have been determining how storage lipids in bats used for fuel are depleted during the winter infection stage in addition to changes in the integumentary lipidome.
Finally, as bats affected by fungal infection show evidence of immune reconstitution inflammatory syndrome, we have used targeted oxylipin analyses to determine lipid mediators involved in inflammation during WNS.