Division
- Immunobiology
Education
- B.S., Biochemistry and Molecular Biology, Biology: University of Georgia, Athens, Georgia
- Ph.D., Cellular and Integrative Physiology: Indiana University School of Medicine, South Bend & Indianapolis, Indiana
- Postdoctoral Fellowship: Washington University School of Medicine, St. Louis, Missouri
Research Interests
My research focuses on developing three-dimensional (3D) imaging to identify and visualize significant physiological and clinical mechanisms in non-invasive and biopsy settings. Early in my training, I explored various research models (e.g., C. elegans, plants, cell culture, mice, pigs) to ask basic research questions about cell cycle, cell wall biodegradability, cancer glycoprotein biomarkers, pulmonary function in premature birth, and pressure-volume relationships of the pig heart. These explorations transitioned to higher-order models and presented technical challenges, many of which required advanced microscopy techniques. Consequently, I became committed to overcoming these challenges to address clinically relevant physiological problems through an interdisciplinary collaborative approach.
To enhance 3D biomedical imaging, my strategy involves three key improvements:
1. Rapid preparation techniques for optical transparency.
2. Efficient acquisition of images from optically transparent tissues.
3. Advanced image processing to improve resolution and analysis of both light microscopy and tomography.
While transparency techniques have existed, they often distort tissues, require hazardous organic solvents, are time-consuming, or involve cumbersome steps. Addressing these issues, I developed ADAPT-3D (Accelerated Deep Adaptable Processing of Tissue for 3-Dimensional Fluorescence Tissue Imaging). This method uses non-toxic chemicals to make biopsies from various species (e.g., mice, pigs, humans) transparent while preserving morphology within one week. For instance, ADAPT-3D processes entire mouse skulls and brains in just six days, maintaining microvascular connections and anatomical integrity while other methods can take up to four weeks. This technique has been successfully applied to multiple tissues, such as liver, heart, brain, and intestines, providing new perspectives on diseases like Crohn’s.
Furthermore, in collaboration with Scientific Volume Imaging Huygens, I optimized deconvolution techniques with depth-variant point spread functions, enabling the acquisition of 3D images up to 500 microns deep using a benchtop epifluorescent widefield microscope. This approach delivers near-confocal resolution in one-tenth the time, at a fraction of the cost. Applications include visualizing plaque deposition in cerebral amyloid angiopathy models and inflammatory phenotypes in ileitis models. Clinically, ADAPT-3D facilitates rapid 3D imaging of kidney biopsies, enhancing visualization of glomeruli and vascular structures, making pathology evaluations more efficient compared to traditional methods.
In non-invasive imaging, I have contributed to enhancing PET imaging of lymphatics, particularly mesenteric routes, by improving resolution through advanced image processing. This work aims to evaluate the safety and efficacy of new PET tracers and visualize fine lymphatic vasculature more effectively. These approaches have great potential to improve pathological evaluations and uncover new mechanistic insights.