Cerebral Micro-circulation and Red Blood Cells


Neurovascular coupling or cerebral functional hyperemia forms the basis for functional brain imaging. Defects in functional hyperemia are believed to contribute to synaptic loss and cognitive decline in multiple neurodegenerative diseases, including Alzheimer disease. To date, significant efforts have been made to identify the mechanisms driving functional hyperemia but the results are debating. Indeed, majority of studies in this field focus on neurovascular unit (i.e., vascular walls, glial cells, and neurons) and the roles of red blood cells (RBCs) are significantly overlooked. Our lab has conducted the first formalized study and unveiled a previously unrealized regulatory role of RBCs in capillary hyperemia in the brain. Our study provides a novel insight to neurovascular coupling in the brain and will have broad impact in functional brain imaging and diagnosis/ management of brain disease.

Long-term Goals: We aim to identify the contributions of RBC-regulated cerebral microcirculation and neurovascular coupling to neurodegenerative diseases and aging.  Our lab is also interested in the development of microdevices for RBC functional assay and diagnosis of disease.

Representative Publications
  1. Wei, H., Kang, H., Rasheed, I-Y., Luo, N., Zhou, S., Lou, N., Gershteyn, A., McConnel, E., Wang, Y., Richardson, K., Palmer, A., Xu, C., Wan, J.,* Nedergaard, M.* (2016) Erythrocytes are oxygen-sensing regulators of the cerebral microcirculation. Neuron, 91, 851-86
  2. Fan, R., Emery, T., Zhang, Y., Xia, Y., Sun, J., Wan, J. * (2016) Circulatory shear flow alters the viability and proliferation of circulating colon cancer cells. Sci. Rep. 6, 27073
  3. Cinar, E., Zhou S., DeCourcey, J., Wang, Y., Waugh, R.E., Wan, J. * (2015) Piezo1 regulates mechanotransductive release of ATP from human red blood cells. Proc. Nat. Acad. Sci. USA, 112, 11783-11788.

Organ-on-a-Chip and 3D Printing

Organ on a Chip

Organ-on-a-chip technology produces 3D mini-organs or tissues in microfluidics, mimicking complex structures and cellular interactions in vivo, and thus provides functional in vitro organ models to study fundamental mechanisms of disease development, drug toxicity screening and drug development. As an emerging concept and a rapid growth field in tissue engineering, organ-on-a-chip technology is expected to revolutionize cell biology in general and the current approaches in tissue engineering and cell culture in particular. My lab is developing microfluidics and 3D bio-printing approaches to construct 1) in vitro biomimetic functional brain-on-chip devices; 2) functional intestine and colon on-a-chip devices by regulating the growth of intestinal organoids in a 3D hydrogel matrix.

Long-term Goals: We aim to establish novel in vitro brain-on-chip devices to investigate the roles of RBC-endothelial interactions in cerebral capillary hyperemia and the dynamics of cerebrospinal fluids near the blood-brain-barrier, which, with unknown mechanisms, play critical roles in brain physiopathology. In addition, we expect to provide in vitro intestinal epithelium models to investigate intestinal stem cells (ISCs)-bacterial interactions and to screen drugs and antibiotics, ultimately leading to new guidelines for prevention and treatment of infectious diseases and intestinal disorders.

Representative Publications
  1. Piou, M., Fan, R., Darling, E., Cormier, D., Sun, J.,* Wan. J.* (2016) Bioprinting cell-laden Matrigel/agarose constructs. J. Biomater Appl., 0885328216669238.
  2. Fan, R., Sun, Y., Wan, J.* (2015) Leaf-inspired artificial microvascular networks (LIAMN) for 3D cell culture. RSC Advances. 5, 90596-90601.
  3. Fan, R., Naqvi, K., Patel, K., Sun, J., Wan, J.* (2015) Microfluidic generation of oil-free cell-containing hydrogel particles. Biomicrofluidics. 9, 052602.

Microfluidics and Emulsions

Microfluidics and Emulsions

The high surface-area-to-volume ratio, superior heat and mass transfer, controlled reagent mixing and improved reaction rates make microfluidics an attractive approach for multiphase processes, reactions, and material synthesis. My lab investigates the dynamics of emulsion droplets and bubbles in microfluidics and develops emulsion-based approaches to produce artificial red blood cells and functional microbubbles for drug and oxygen delivery and biomedical imaging. In addition, we identified, for the first time, the regulatory roles of flow in the anodic growth of TiO2 nanotubes and demonstrated that flow not only controls the diameter, length, and crystal orientations of TiO2 nanotubes but also regulates the spatial distribution of nanotubes inside microfluidic devices and orientation on silicon substrates. Our approach provides a promising strategy to integrate silicon with hierarchical TiO2 nanotube arrays that may find applications in biomedical devices, nanoelectronics, silicon-based photonics, and photovoltaic solar cells. Most importantly, the demonstrated role of flow in anodic growth of TiO2 nanotubes may apply broadly to a many electrochemical reactions where the local mass transport plays a critical role in reaction kinetics and material synthesis.

Long-term Goals: My lab aims to establish a robust program to explore microfluidic approaches to 1) synthesize biologically inspired functional materials, and 2) control electrodeposition and electrochemical synthesis of nanomaterials for clean energy production and storage.

Representative Publications
  1. Fan, R., Chen, X., Wang, Z., Custer, D., Wan, J.* (2017) Flow-regulated growth of titanium dioxide (TiO2) nanotubes in microfluidics. Small, 13, 1701154. (Featured as a frontispiece article).
  2. Lu, T., Fan, R., Delgadillo, L., Wan, J.* (2016) Stabilization of carbon dioxide (CO2) bubbles in micrometer-diameter aqueous droplets and the formation of hollow microparticles. Lab On Chip. 16, 1587-159 (Featured as a cover article)
  3. Koppula, K. S., Veerapalli, K. R., Fan, R., Wan, J.* (2016) Integrated microfluidic system with simultaneous emulsion generation and concentration. J Colloid Interface Sci.466, 162-167.