Development of New Tools
We are interested in establishing new tools and methods to study (1) brain microcirculation; (2) brain metabolism; (3) neural circuit mapping; and (4) brain tumor.
SIMPLE–Precise control of ischemia with magnetic force
Currently, it is difficult for researchers to take advantage of advanced live-imaging technologies in stroke studies, particularly in the developing mouse brain, due to vascular surgical challenges. We have developed a novel approach to induce focal ischemia with precise control of infarct size and occlusion duration in mice at any postnatal age (Jia et al., Nature Methods, 2016). We achieved the occlusion, which is reversible, via micromagnet-mediated aggregation of magnetic nanoparticles within a blood vessel (see below). In combination with longitudinal live imaging, we will investigate underlying mechanisms of disruption and repair of neurovascular units in vivo under ischemic stroke.
We named it SIMPLE, Stroke Induced by Magnetic ParticLEs.
Understanding tumor metabolism holds the promise of new insights into cancer biology, diagnosis and treatment.
Targeting tumor metabolism has re-emerged over the last decade as a potential source of new cancer therapies. There are several means by which human gliomas metabolism has been assessed: through the metabolome of plasma collected from the cubital vein, through metabolomics analysis of blood collected from resected cancer tissue or cerebral spinal fluid, through imaging with NMR and through assessment of isotope enrichment in glioma tissue after intra-operative infusion with 13C-labeled nutrients. To date, however, direct measurement of metabolites consumption and production by gliomas in patients is technically difficult.
To assess human cancer metabolism, we developed a novel method to collect intra-operative samples of blood from an artery directly upstream and a vein directly downstream of a brain tumor, as well assamples from dorsal pedal veinsof the same patients. After performing targeted metabolomic analysis, we have characterized the metabolites that are consumed and produced by gliomas in vivoby comparing the arterial supply and venous drainage. Through paired comparisons of upstream and downstream samples from the same patient, we are able to exclude the inter patient variation that is present in plasma samples usually taken from the cubital vein. We named this method, CARVE–Cancer Arterial-Venous analysis.
Mapping of Brain Metabolism
(Ongoing, with Wenzhi Sun and Zeping Hu lab).
Hard tissues including bones and teeth are still the most difficult organs to be cleared. In addition, loss of endogenous fluorescence remains a major concern for solvent-based clearing methods. We are proud to support Prof. Hu Zhao’s lab from Texas A&M University in developing a polyethylene glycol (PEG)-associated solvent system (PEGASOS), which rendered nearly all types of tissues transparent and preserved endogenous fluorescence (See images below, imaged and provided by Hu Zhao's lab). The PEGASUS method, which Hu Zhao and his colleagues invented, can turn the whole adult mouse body transparent and image different organs including bones, teeth, brain, muscles, and other tissues with no blind areas. Working with Zhao lab and Sun lab, we will use this method to image the blood vasculature and glial cells in rodent brains or tissues from patients.