- Post Doctoral
MIT Unit Affiliation:
- Biological Engineering
- Chemical Engineering
Post Doc Sponsor / Advisor:
Date PhD Completed:
Top 3 Areas of Expertise:
I am broadly interested in the application of supramolecular principles to the design of new therapies. This will encompass new routes for drug delivery and biomaterial generation, with use in treating cancer, diabetes, inflammatory diseases, and cardiovascular disease. Specific areas of interest include peptide self-assembly, host-guest mediated therapeutic targeting, and recombinant protein engineering of hydrogel materials.
Expected End Date of Post Doctoral Position:
-Responsive supramolecular peptide assemblies
-Host-guest mediated drug delivery strategies
-Protein engineering of viral biomaterials
A diverse family of self-assembling peptide amphiphiles (PA) has shown promise as therapies for regenerative medicine. One broad target of interest is angiogenesis, the growth of new blood vessels, which could help to improve blood flow in ischemic cardiovascular diseases. New clinical strategies for cardiovascular disease have evaluated the delivery of potent proteins or stem and progenitor cells to improve angiogenesis and tissue repair. Here, several approaches using supramolecular PA nanofibers were evaluated as therapeutic strategies for cardiovascular disease and blood vessel growth. The first objective used a heparin-binding PA system to facilitate controlled angiogenic growth factor retention and delivery, demonstrating enhanced tissue vascularization and significant functional improvement in a mouse model of myocardial infarction and a rat model of hindlimb ischemia. The second objective developed a PA-based delivery matrix to facilitate cell-based therapies in cardiovascular disease through the use of PA nanostructures displaying a cell adhesion epitope to improve the retention, support, viability and therapeutic activity of bone marrow cells. This approach demonstrated significant improvement in a mouse hindlimb ischemia model. The third objective developed PA nanostructures that mimicked the activity of a potent angiogenic protein, VEGF, by activating VEGF receptors and promoting angiogenesis. The prolonged retention and potent VEGFmimetic activity of the bioactive PA in ischemic tissue promoted significant functional improvement in a mouse hindlimb ischemia model. One final objective was to develop new bioactive PA nanostructures that could provide spatiotemporal control for drug or protein delivery or could localize the delivery of important signaling gases such as nitric oxide or carbon monoxide for cardiovascular therapies. Such materials could improve cell or tissue survival following ischemia by promoting anti-inflammatory activity. In conclusion, the strategies developed here may improve the efficacy of angiogenic or cell-based therapies for cardiovascular disease through the use of well-defined, versatile, and highly bioactive nanostructures.