The research in Dr. Goldspink's lab centers around two thematic areas:
- Improving cardiac muscle contractile function during disease and failure.
- Enhancing cardiac repair and regeneration using stem cells and biomimicry.
Intersecting these two areas of cardiac muscle function and biology is the influence of insulin-like growth factor-1 isoforms and their function.
Pleiotropy is the phenomenon whereby a single gene has multiple consequences in numerous tissues. IGF-1 exerts pleiotropic effects on numerous tissues by influencing different cellular processes such as proliferation, protein expression, growth and metabolism. The IGF-1 gene gives rise to different isoforms in various tissues during development, in response to hormonal stimulation, nutrition, aging and disease. An underlying hypothesis of this research is the pleiotropic actions of IGF-1 (and the IGF system), are manifest in isoform function. Consequently, we are investigating the role of IGF-1 isoforms in response to stresses such a mechanical overload, hypoxia and oxidative stress in the heart.
We have focused on a particular isoform of IGF-1, called Mechano-Growth Factor (MGF), which plays a protective role in preventing cell death, preserving contractility and preventing hypertrophy of the heart following myocardial infarction. We are currently investigating the underlying mechanisms by which this occurs utilizing peptide analogs to examine the functional regions of MGF. In addition, we are examining the regulation of the isoforms to better understand the function biology of the IGF-1 isoforms in general.
This work continues to grow in a number of different directions. We are presently investigating the influence of these IGF-1 isoform peptides on resident cardiac stem/progenitor cells, with a view of using them to enhance cardiac repair. We are exploiting these findings in a number of different ways. We (and collaborators) have developed a technology that combines a microscopic physical scaffold, to provide the physical cues tissue growth combined with the capacity to deliver peptide therapeutics.
The goal is to develop a “biomimetic” approach that optimizes stem cell therapy. This approach of implantable cell-sized “biomimetic devices” could serve to instruct cells in order to enhance natural tissue repair and regeneration in other tissues as well as the heart.