Bioengineering and chemical engineers contribute significantly toward the engineering of complex, multicellular systems. However, we need to better understand how to manipulate organ size, shape and function. Engineers bring a diverse and versatile “toolkit” to decipher mechanisms of organogenesis and intercellular communication: solving reaction-diffusion and transport problems, utilizing control and decision theory, applying quantitative and statistical methods of analysis, and employing experimental knowledge in the analysis of soft materials.
The research focus of the lab can be classified into these areas:
Biophysics of epithelial organ development and morphogenesis
There is a great need to study developmental biology from an engineering perspective to develop new strategies for building tissues and treating degenerative tissue diseases. Probing animal development with quantitative tools can potentially improve traditional methods of tissue engineering as well as inspire completely novel methods for creating synthetic organs. Toward this end, the research program in the lab focuses on integrating chemical and mechanical signaling at the tissue scale through advancing the state of the art for in vitro tissue culture and utilizing computational modeling of tissue patterning and morphogenesis.
The fruit fly, Drosophila, has served as an important model system for identifying tumor suppressor genes, which are conserved in humans as well, and due to the genetic tools available is one of the main model systems investigated by the lab.
Growth control of epithelial tissues in development and regeneration
Understanding how individual cells and whole organs regulate their size is essential to developing new techniques in treating cancer (too much growth). A related question is how to cell signaling to improve or increase the potential for regeneration in wounded tissues.
Currently lacking is a quantitative understanding of how cells incorporate external inputs from their surroundings to regulate final tissue size. Our lab employs live imaging using confocal microscopy, quantitative data analysis and modeling to further our understanding the regulatory network determining robust growth control.
Advancing cell and organ culture methods for preclinical disease modeling
Cell culture. In recent years, insect cells have become important for heterologous recombinant protein production using the baculovirus expression system. Developing a better quantitative understanding of the metabolism and kinetics of insect cell growth will significantly improve the production process of novel therapeutics and vaccines.
We are developing advanced chemically defined media for Drosophila cells, which enables greater control for biochemical studies. We envision that such efforts will help us to identify novel factor(s) affecting cell growth and differentiation.
Organ culture. Organ development and homeostasis are directed by a “symphony” of signals. However, the mechanisms integrating hormonal, environmental, and genetic inputs to control the size, shape, and identity of multicellular compartments in the body remain an open question with significant implications for stem cell engineering and regenerative medicine. To investigate the crosstalk between different signaling modalities, new methods are required that provide a controlled microenvironment with cellular resolution imaging capabilities.
Current research focuses on identifying extrinsic growth factors and improving media for Drosophila wing imaginal discs, an established model for studying the genetics and biophysics of growth control. We are also developing “Drosophila-on-a-chip” devices .