As a doctoral candidate, my research focused on the design of gene vectors for the treatment of cystic fibrosis. My doctoral dissertation was titled “Mucosal Barriers to Non-Viral Gene Delivery in the Cystic Fibrotic Lung.” This project involved three main facets including: (i.) the formulation and characterization of polymeric and liposomal gene delivery systems, (ii.) the development and characterization of in vitro models for testing the efficiency of gene delivery systems, which included mucus from cystic fibrosis patients, synthetic mucus used to mimic lung mucus, and lung cells grown in polarized monolayers, and (iii.) the development and application of sophisticated techniques for comparing the efficiency of nano-sized gene delivery systems at overcoming biological barriers, which included flow cytometry, electron microscopy, confocal and epiflourescent imaging, multiple particle tracking, rheology, light scattering, and quantitative and statistical image analysis. The work included in my doctoral dissertation resulted in 6 publications (3 in press and 3 in preparation or submitted), a book chapter, two patents, 9 podium presentations, 6 poster presentations, and 7 awards, including an NSF fellowship and prestigious drug delivery awards from the International Society of Aerosols in Medicine and Capsugel/Pfizer.
After graduation, I was eager to pursue a more translational postdoctoral training position related to the design and delivery of cancer therapeutics. Thus, I joined Dr. Rakesh Jain's laboratory at Massachusetts General Hospital, where I continue to focus on gene delivery using cell-based delivery systems. Specifically, I am designing genetically engineered mesenchymal stem cell-based therapeutics for the treatment of solid tumors. The ability to engineer cells and infuse them into the body to serve as therapeutic vehicles has become increasingly feasible in recent years. The advantage of cell-based delivery protocols resides in their ability to incorporate into tumor tissues and release locally sustained levels of therapeutic cytokines. To facilitate the production of mesenchymal stem cell-based therapeutics, my project has focused on the three primary aspects: (i.) the characterization of the phenotype of bone marrow-derived mesenchymal stem cells, (ii.) the development of quantitative homing assays for studying the migration of different bone marrow stroma-derived cell populations to tumors, and (iii.) the development of genetically-altered stem cell therapeutics, which have been tested in mouse models of neoplasia. Using multiphoton laser scanning microscopy, we have tracked intravitally the recruitment and engraftment of bone marrow derived stromal cells in tumors. I hope this training experience will help me to develop vital insight into the biological response to therapeutics, which is essential in the development of drugs that can overcome biological barriers to treat human disease.