(6dh) Targeted Intracellular Delivery of Drugs and Genes

With the advent of genomic biomarker signatures of disease and discoveries of new genotype?phenotype associations, the concept that therapy can be customized to the individual is emerging. My future research interests lie in the targeting of cancer cells for diagnosis and treatment using nanoscale delivery systems. Between my graduate and post-doctoral work, I have gained experience in both polymeric and liposomal drug and gene delivery systems as well as targeted and non-targeted delivery for both therapeutic and diagnostic purposes. I am interested in bringing these together to continue and also to expand upon the research I have begun in using DNA-based engineered constructs to deliver anticancer agents to the cell nucleus.

My PhD thesis, with Justin Hanes, in the Chemical & Biomolecular Engineering Department at Johns Hopkins, focused on the synthesis and characterization of improved non-viral gene delivery systems; specifically high-density nanocomplexes composed of numerous copies of plasmid DNA and the cationic polymer polyethylenimine (PEI). This included the encapsulation of DNA and PEI/DNA nanocomplexes within polymer microparticles. As an additional project, I also studied the effect of delivering combined chemo- and immunotherapy via polymer systems to malignant glioblastoma. In order to complete these studies, I became proficient in making a variety of polymer-based drug delivery systems and characterizing them using sizing techniques from the nano- to the micro-scale (dynamic and static light scattering, transmission and scanning electron microscopy (TEM and SEM), and the Coulter Principle). These studies were primarily in vitro experiments, consisting of cell culture where FACS and protein expression assays were used. While obtaining my PhD, I was awarded an Abel Wolman Fellowship, awarded on a school-wide basis to outstanding beginning PhD students in engineering, and I passed the Chemical Engineering Qualifying Exam with Honors. I also spent 4 semesters as a teaching assistant for a course entitled, ?Engineering Aspects of Controlled Drug Delivery?.

As a post-doctoral fellow, I am working with George Sgouros, in the Radionuclide Therapy and Dosimetry Research Lab at the Johns Hopkins School of Medicine. I began my post-doc using alpha particle emitting radionuclides to target and treat ovarian cancer metastases with antibody and immunoliposomal delivery systems, and have recently begun targeting prostate cancer using aptamers. Since starting, I have applied for, and received a National Research Service Award (NRSA) from the National Cancer Institute to radiolabel DNA with alpha particles in order to generate a more efficient cell kill due to intracellular perinuclear localization of the alpha-emitter. I am also involved in collaborations in which liposomes encapsulate magnetic resonance (MR) contrast agents as imaging tools, or as models for drug delivery. The liposomes targeting specificity is analyzed using FACS, radioactivity, and/or confocal microscopy in vitro, or in vivo using small animal imaging (μSPECT/CT, MR, fluorescence). Both the ovarian cancer work and the contrast agent work have been submitted as abstracts at this conference.