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The objective of the McGuigan lab is to develop experimental systems to understand and control cellular re-organization for tackling problems in regenerative medicine.

Currently in the lab we are developing technologies to control cell organization, localized cell-cell signaling, cell-alignment and cell migration. Using high-throughput microscopy we are also quantifying cell re-organization in our engineered systems to define cell behaviour during different re-organizational processes.

We are applying our organizational control strategies to address regenerative medicine problems such as engineering artificial tissues, identifying methods to modulate angiogenesis and wound healing, and developing in vitro drug screening models.

Our team is extremely multi-disciplinary in nature and contains, post-doctoral fellows, and graduate and undergraduate students who are biologists, engineers, chemists, mathematicians and clinician scientists.

Current Projects

Technology development

 

 

i) Micropatterning technology: We have developed a number of methods to control the organization of mulitple populations of cells in two and three-dimensions. Some of our methods utilize soft-lithography and microfabrication and allow precise control over pattern sizes and shapes. Other methods do not require complex fabrication techniques and are based on simple parafilm inserts, making these methods widely accessible to the biology and bioengineering community.

ii) Gene expression patterning technology: We are developing methods to pattern gene expression within sheets of tissue in vitro. Gene expression patterns are critical during embryo development and tissue morphogenesis to ensure correct tissue specification and organization. Our tools will allow us to manipulate tissue morphogenesis in vitro and understand the importance of different gene expression patterns during tissue assembly.
iii) Cellular alignment technology: Aligned topography is a mechanism to control cell alignment during morphogenesis in the embryo. We have developed a nanogrooved polymer substrate in a 96-well plate format for high throughput study of this contact alignment phenomenon in single cells and collective sheets of cells.
iv) Migration guidance technology: Cell migration is a critical component of tissue re-organization. We are currently developing high-throughput devices that use chemical and mechanical cues to guide the migration of single cells and groups of cells in vitro.

Tissue Engineering Applications

 

i) Epithelial tissue engineering: Epithelial cells line most of the major organs of the body as sheets of epithelial tissue. Engineering functional epithelial sheets is therefore important for generating functional artificial organ replacements since most require an epithelial component. In collaboration with Toronto General surgeon Thomas Waddell, using our alignment and genetic patterning tools we are attempting to engineering functional epithelium for incorporation into engineered tracheas.

ii) Blood vessel engineering: Cardiovascular disease is the leading cause of death globally. One strategy to address this clinical problem is to tissue-engineer replacement blood vessels by growing cells in a natural or synthetic matrix and biomechanically conditioning the vessels for several months. While the efficacy of this approach appears promising, the time between cell harvesting and implantation of the resulting vessel is typically three to nine months. We are attempting to identify mechanisms to control cell organization in blood vessels to accelerate tissue maturation and allow implantation into patients at earlier time points.

In vitro screening Applications

 

Epithelial "micro" tissues: About 90% of human cancers arise in epithelial tissues therefore this is a very interesting tissue to study cancer in vitro. We are developing high-thoughput methods to generate 2D "micro" epithelial tissues for understanding mechanisms of cancer progression and for the development of novel therapeutics.

Modular tissues: Modular tissue engineering allows the assembly of complex 3D tissue structures from microscale modular components. We are currently developing in vitro methods to assembly modular tissues for drug screening applications.
© 2008 Page last edited 4/1/12