Stephanie Willerth

Stephanie Willerth

Associate Professor   

S.B. (Chemical Engineering) MIT
S.B. (Biology) MIT
M.S. Washington University in St. Louis
Ph.D. Washington University in St. Louis
PEng


Contact Information

Engineering Office Wing, Room 513
Tel: 250-721-7303
Fax: 250-721-6051
Email:willerth@uvic.ca
Lab Website

Research Areas

  • Tissue engineering
  • Regenerative medicine
  • Biomaterials scaffolds for controlling stem cell differentiation

Research Description

Tissue engineered scaffolds for promoting stem cell differentiation
One area of research focuses on developing 3D biomaterial scaffolds containing cues, such as growth factors, for directing stem cell differentiation into specific phenotypes for tissue engineering applications. Such scaffolds can also be used to study stem cell behavior in an environment that replicates the stem cell niche as opposed to using traditional 2D culture methods. Specifically, we study the behavior of both embryonic stem (ES) and induced pluripotent stem (iPS) cells inside of 3D scaffolds. IPS cells are derived from somatic cells and demonstrate many of the properties of ES cells. IPS cells are generated from adult somatic cells, such as fibroblasts, by upregulating the expression of specific genes that restore pluripotency. The use of iPS cells allows for generation of pluripotent cell lines without the use of embryos. An additional advantage is that patient specific iPS cell lines can be produced, enhancing their therapeutic value by potentially reducing the immune response against the transplanted cells. Analyzing the behavior of these iPS cells inside of 3D scaffolds in response to different cues will allow for engineering of replacement tissues with the eventual goal of clinical translation.

Novel drug delivery systems
Our second area of research focuses on developing novel drug delivery systems to control the release of target molecules that promote tissue repair. Affinity-based delivery system provide such a method as these systems rely on non-covalent interactions between the target molecule and the scaffold material to produce controlled drug release as opposed to relying on diffusion to regulate release. This work involves developing a method for generating controlled release of heat shock proteins to promote tissue regeneration after injury. In normal cells, heat shock proteins (HSPs) act as chaperones by helping fold nascent polypeptide chains into functional proteins. Additionally, HSP expression is upregulated in response to cell stress. Although their cytosolic roles in the stress response have been well characterized, recently HSPs were discovered to have beneficial properties when administered exogenously to cells. Specifically, various heat shock proteins, including Hsp27, 70, and 90, can inhibit neuron degradation as well as contribute to axonal outgrowth when applied exogenously to the site of nerve injury. It is hypothesized that when delivered extracellularly, these HSPs can prevent protein aggregation and help preserve protein function after cell injury and that HSPs can also be taken up by surrounding cells, enhancing their chance of survival.

Analyzing mechanisms of stem cell differentiation using next generation sequencing
The recent development of “next generation” sequencing technologies, such as Illumina and 454, provide a way to perform high-throughput DNA sequence for a relatively low cost. “Next generation” DNA sequencing requires large amounts of DNA (5-10 µg) to generate a library for the sequencing process. During my post doctoral research, I developed a novel method for amplifying small amounts of RNA into the large quantities of DNA necessary for library generation. This method was initially used to sequence and analyze clinically relevant HIV populations. It also can be applied to a variety of biological problems where low amounts of genetic material are obtained due to scale up limitations, such as the stem cell cultures.  Thus, this method provides a potential means of sequencing RNA transcriptomes for studying the processes that control stem cell differentiation. This area of research focuses on using these “next generation” sequencing technologies to compare the differences in gene expression by ES and iPS cells grown in 2D versus 3D scaffolds.