Bioengineering and chemical engineers contribute significantly toward the development of therapeutics to treat human diseases and are involved in the engineering of complex, multicellular systems for regenerative medicine. However, biological systems are extremely complex! There is a critical need to develop and apply methods to reverse-engineer the control mechanisms that regulate organ development and homeostasis. 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.
At heart, we are interdisciplinary scientists and engineers tackling the most fundamental, unsolved problems in cell and developmental biology. We have experience in both experimental and computational biology techniques.
The research focus of the lab can be classified into multiple areas:
Understanding the basis of birth defects: The biophysics of epithelial organ development and morphogenesis
There is a great need to study developmental biology, regeneration and cancer 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.
What causes cancer or prevents tissues from healing? Reverse-engineering 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.
Can we identify new drug targets and methods to promote health? 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 have developed 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 have developed new organ on a chip and “Drosophila-on-a-chip” devices to study the fundamental rules underlying the development of multicellular systems.
Engineering in vivo model systems for disease modeling and drug discovery. Despite the time, capital, and human resources devoted to developing successful therapeutics, ~90% of drug candidates in clinical trials fail (1). Of these failed clinical trials, the majority were due to either lack of clinical efficacy (~52%) or safety (~24%) (2). A large portion of these failures can be attributed to novel therapeutics having been developed from translational model organisms. Although many model organisms share homologous genes with human genes (with high sequence identity), most animal models and gene homologs do not fully recapitulate the human diseases they are intended to model. To increase the likelihood of clinical relevancy and translational properties of novel therapeutics, we are utilizing the powerful genetic tools available in Drosophila melanogaster to engineer disease-specific models. These efforts combine:
- The high-throughput, low-cost, and short time-scale (relative to other model organisms) of using Drosophila melanogaster
- The genetic tools to create more relevant disease-models
- Our customized high-throughput machine learning pipeline that characterizes phenotypic abnormalities associated with abnormal gene expression
We are actively developing a platform to enable rapid identification and testing of small molecule inhibitors in a preclinical, in vivo model for any gene-related disease. For any given disease-associated gene and a compound library, we can utilize our platform and genetic tools to identify potential lead candidates for clinical trials with the potential for increased translational efficacy. In support of this effort, we are members of the ND Warren Center for Drug Discovery.
If you are interested in pursuing a Ph.D. in these areas, please reach out to us.