My research laboratory works at the interface of engineering and medicine, applying new advances to important clinical laboratory problems. Specifically, a principal focus of my professional research interests is in translating technological developments in optics and machine learning into practical approaches to problems in diagnostic pathology.
One such project has been for the development of a practical technique and instrument for non-destructive three-dimensional reconstruction of histology, applied to both human and animal specimens. In continuing experiments we are using new approaches to chemical clearing of tissue and imaging based on rapid multiphoton laser systems for evaluation of pathology specimens, from both humans and animal models of disease. This technique presents numerous potential advantages over traditional methods in terms of completeness of analysis, preservation of tissue for advanced molecular studies, and examination of important parameters such as architecture and abnormal growth, all while maintaining the compatibility with traditional histologic analysis. It is a clear illustration of the benefits afforded by these new optical techniques and an important step in the further development of advancements in microscopy.
We began experiments for optimizing and expanding the role of clearing with benzyl alcohol benzyl benzoate (BABB) and multiphoton imaging around 2008, work that was initiated in close collaboration with Michael Levene, PhD. The clearing agent BABB has been known for many decades, but the advent of optical sectioning microscopy has magnified its utility. While several new clearing techniques have evolved over the past several years, many of them featuring in prominent publications, we have focused on maximizing the use of the BABB approach given that it has enormous potential in its current form to impact the manner in which histologic analysis for both research studies and clinical diagnostics is practiced. In continuing experiments we are using newly developed approaches to pre-clearing processing and adapting advanced imaging systems to evaluate research and pathology specimens from a broad range of sources, including kidney, lung, prostate, thyroid, bone marrow, and breast tissue. This technique presents numerous potential advantages over traditional methods in terms of completeness of analysis, preservation of tissue for advanced molecular studies, and examination of important parameters such as architecture and abnormal growth, all while maintaining the compatibility with traditional histologic analysis. It's application to animal models of chronic kidney disease have begun to reveal surprising new aspects of the natural history, morphologic lesion, and pathophysiology of CKD. Human renal specimens have begun to show potential new avenues for diagnostic interpretation. They are a clear illustration of the benefits afforded by these new optical techniques and an important step in the further development of advancements in microscopy.
Furthermore, the three-dimensional imaging with digitization of morphologic data, together with the access to genomic sequencing, result in generation of vast amounts of information which require computing management and analysis tools in order to yield utility. As such, an important component of work done in our laboratory, headed by Eben Olson, PhD, involves current and former trainees with specialized knowledge of powerful new computing tools for imaging and genomic data management. The developments are demonstrating that newest image pattern recognition techniques based on convolutional neural networks and python programming modules, to which our lab contributes, can be employed to aid in the accurate characterization of a broad range of interpretative areas.
From a purely clinical perspective, my interests are in instrumentation, pathology informatics, general coagulation testing, and flow cytometry for hematologic disease.
Education & Training
- MSYale School of Engineering and Applied Science (2007)
- MDYale University (1999)
- BSStanford University (1994)
- FellowYale University School of Medicine
- ResidentYale-New Haven Hospital
- Board CertificationAB of Pathology, Anatomic & Clinical Pathology (2005)
- Board CertificationAB of Pathology, Hematology (Pathology) (2005)