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Novel Tools for Cellular Biomechanics

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An Interview with Dr. Jiandi Wan, Assistant Professor, Microsystems Engineering, Rochester Institute of Technology.

Recent recipient of a $476,505 award from the Gordon and Betty Moore Foundation, Dr. Wan tells us about his career and the work his lab is doing to advance understanding of cellular biomechanics using microfluidics.

Q. How did you become interested in science?

A. I have been a curious person since I was a kid and always eager to know why. My PhD study was in physical chemistry, where I studied the photon-induced electron transfer process in organic and synthetic biological systems and obtained deep understanding of scientific principles at the molecular level. With additional post-doctoral training in the field of applied science and engineering at Harvard and Princeton, I started to learn how to combine science and engineering approaches to study fundamental problems. The combination of molecular understanding with quantitative approaches made me enjoy exploring interesting scientific questions and become more interested in science and engineering. 

Q. What have some of your most rewarding achievements been so far?

A. Since my PhD study, I have conducted a wide range of research projects in chemistry, biology, materials, and fluid dynamics. I have learned a lot and benefited from my study by developing a broad understanding of scientific and engineering principles. Some of the projects are straightforward but I needed to think outside of the box to solve the problem. The other projects are quite practical and we have several patients for them. There are also projects that require interdisciplinary expertise to achieve success. There are several examples I can remember, one in particular is to study red cell mechanosensing. 

Q. Can you tell us about your lab's main research directions?

A. The broad objective of my research is to explore dynamic processes spanning from cerebral microcirculation, microvascular and tissue engineering, to complex fluids, emulsions and functional materials. My group takes microfluidics together with state-of-art nanofabrication and in vivo imaging techniques as the main technical approach to investigate emerging challenges in brain function, tissue engineering, and advanced materials. The mission of my research is to advance our fundamental understanding of dynamic processes in these fields and develop novel technologies, devices, and materials to improve biomedical therapeutics and clean energy production.

I have three Research Thrusts:

1. Cerebral Microcirculation and Biomechanics.  My lab focuses on cellular biomechanics and develops novel in vitro biomimetic approaches to recapitulate in vivo microenvironments in cerebral microcirculation. We investigate mechanisms of cellular responses to controlled external stimuli and re-examine the results by in vivo animal studies. The understood mechanisms are then used to manipulate cellular behaviors in vivo and provide potential therapeutic strategies. Specifically, our lab has investigated mechanistically the effect of fluid shear stress on the cellular behaviors of red blood cells, blood progenitor cells, and circulation cancer cells, and capillary functional hyperemia in the brain. 

Jiandi has recently received a $476,505 award from the Gordon and Betty Moore Foundation, for work researching the impact of shear stress on cell circulation and the spread of disease. Further details of the work and its implications can be found here. https://www.rit.edu/news/story.php?id=59056 

2. Microvascular and Tissue Engineering. My lab now focuses on the development of microfluidic and bioprinting approaches to regulate the proliferation and differentiation of intestinal stem cells (ISCs) in 3D hydrogel matrix and grow intestinal organoids and functional intestinal epithelial layers. We construct microvascular networks in 3D matrix as an effective perfusion systems to conduct sustained ISCs culture.  

3. Complex Fluids and Advanced Materials. My lab develops microfluidic and nanofabrication approaches to investigate fluid and interfacial dynamics at low Reynold’s numbers. We further integrate synthetic chemical methods and biological processes with fluids and produce novel advanced functional materials for health and energy applications. In particular, our lab investigates the controlled production of multiphase emulsion droplets in microfluidics and use of the emulsion drops as the templates for synthesis of artificial red blood cells, ultrasound microbubbles, and porous carbon microspheres. Currently we focus on the synthesis of TiO2 nanotubes in microfluidics and construct optofluidic devices to detect label-free protein/nanoparticle dynamics.

Q. What are some of the difficulties of investigating cellular biomechanics?

A. Biomechanics is a very interesting research topic and also has a significant impact on our real life. The bones for example are always under mechanical stress. Red blood cells, on the other hand, also experience continuous shear stress while flowing in our circulation system. One of the challenges in biomechanic studies, from my point of view, is how to couple molecular, cellular, and tissue responses to applied stress, which covers a wide length scale (i.e., from sub-nanometer, to center meters) and requires both biological, chemical, and mechanical expertise.  

Q. What future work do you have planned?

A. We have several long-term goals, including:

- Exploring the roles of mechanics and mechanobiology of circulating blood cells in the regulation of cerebral microcirculation. We expect to provide new insights to the neurovascular coupling in the brain and offer novel therapeutic strategies to treat neurodegenerative disorders.

- To construct functional artificial intestine and/or colon from ISCs and investigate ISCs-bacterial interactions in vitro and in vivo. We will develop novel microvessel models in microfluidics and study the dynamics of tumor invasion. We expect to provide novel intestinal epithelium models for drug and antibiotics screening, and offer new guidelines for prevention and treatment of infectious diseases and intestinal disorders.

- To develop artificial red blood cells-based drug delivery systems and produce novel ultrasound microbubbles to measure in vivo pressure in the circulation. 

- To produce porous carbon spheres with controlled size and morphological features as the active material for capacitive energy storage in electrochemical flow capacitor. We plan to develop TiO2 nanotube-based microfluidic approaches to conduct CO2 reduction and solar fuel production. 

To follow progress of this work and other research from Jiandi’s lab, please visit https://sites.google.com/site/jiandiw/