Hannah Storrie
Postdoctoral Fellow
hstorrie@deas.harvard.edu

Education

Northwestern University, Evanston, IL - Ph.D., Materials Chemistry, December 2004

Barnard College, New York, NY - Bachelor of Arts, Chemistry, 1999

Research Focus

Delivery of vascular growth factors for neural tissue engineering

Few treatment options exist for diseases and traumas of the nervous system due its limited regenerative ability. Recently, cues provided by the vascular system have been implicated in neuroprotection and regeneration in the central nervous system. We propose that the sustained delivery of vascular endothelial growth factor (VEGF) from a polymeric drug delivery system may provide signals to promote axon regeneration in a peripheral nerve model system. Delivery of VEGF from a polymeric system provides sustained release of the growth factor over time, maintaining an effective concentration of factor at the site of injury without the need for multiple injections or producing systemic side effects.

We are investigating the use of an injectable alginate hydrogels for growth factor delivery. Alginate, a polysaccharide derived from brown algae, is composed of mannuronic and guluronic acid blocks. By controlling polymer characteristics, such as molecular weight, degree of oxidation, we can control the kinetics of factor release and gel degradation. Hydrogels are formed from alginate solutions upon addition of a crosslinking agent, such as calcium ions, and growth factors can be encapsulated during crosslinking to provide sustained release of therapeutic concentrations over a period of weeks.

A peripheral nerve regeneration model is being used to evaluate the efficacy of VEGF delivery on the maintenance and regeneration of the neuromuscular junction (NMJ). Peripheral nerves are capable of regeneration, which allows for easy evaluation of the efficacy of VEGF delivery on axon regeneration and provides a model for understanding the mechanisms of axon regeneration. In vivo experiments have been carried out in transgenic C57BL/6 mice selectively expressing yellow fluorescent protein (YFP) in their motoneurons. In a double nerve crush model, first, the nerve of the sternomastoid muscle is crushed with a forcep, damaging axons distal to the crush, then, three days later, the nerve is crushed again and blood supply to the muscle is ligated. At the time of the second crush, either blank or VEGF containing alginate gels are placed on top of the muscle prior to suturing of the incision.

Flourescence confocal microscopy can be used to directly image regenerating axons at the NMJ. Acetylcholine receptors (AchR) found in the muscle fibers are stained with Alexa594 α-bungurotoxin, and axon maintenance and regeneration is monitored for up to 3 weeks following the second nerve crush.

Publications

• Storrie, H.; Mooney, D.J. Sustained delivery of plasmid DNA from polymeric scaffolds for tissue engineering. Advanced Drug Delivery Reviews. In press.
• Zhao, B.Q.; Wang, S.; Kim, H.Y.; Storrie, H.; Rosen, B.R..; Mooney, D.J.; Wang, X.; Lo, E.H. Role of matrix metalloproteinases in delayed cortical responses after stroke. Nature Med. 2006, 12(4), 441-445.
• Beniash, E.; Hartgerink, J. D.; Storrie, H.; Stupp, S.I. Self-assembling peptide amphiphile nanofiber matrices for cell entrapment. Acta Biomaterialia. 2005, 1, 387-397
• Storrie, H.; Stupp, S.I. Cellular response to Zinc containing Hydroxyapatite: An in vitro study of proliferation, alkaline phosphatase activity and biomineralization. Biomaterials. 2005, 26, 5492-5499.
• Bergquist, C.; Storrie, H.; Koutcher, L.; Bridgewater, B.; Friesner, R.; Parkin, G. Factors influencing the thermodynamics of zinc alkoxide formation by alcoholysis of the terminal hydroxide complex, [Tp(But,Me)]ZnOH: An experimental and theoretical study relevant to the mechanism of action of liver alcohol dehydrogenase. J Am Chem Soc. 2000, 122, 12651-12658.
• Milkevitch, M.; Storrie, H.; Brauns, E.; Brewer, K.J.; Shirley, B.W. A new class of supramolecular, mixed metal DNA-binding agents: The interaction of Ru-II, Pt-II and Os-II, Pt-II bimetallic complexes with DNA. Inorg Chem. 1997, 36, 4534-4538.