Cell-specific targeting, receptor-ligand interactions, lung cancer, drug delivery, cancer biomarker identification
A significant goal in medicine is the development of methods for cell-specific targeting of therapeutic molecules. While the concept of the “magic bullet drug”was introduced over 100 years ago, medicine has yet to realize this goal. Our laboratory is developing platform technologies to identify targeting reagents that can home to specific cell types in vivo. The current scientific goals of the research group are to:
- Develop comprehensive technologies that enable cell-specific delivery of biologically active molecules in vivo;
- Map unique cellular features of the cell-surface that can be exploited as recognition moieties for cell-specific delivery; and;
- Understand how the cell surface reorganizes in response to a disease state. Our approach is multi-faceted encompassing biochemistry, organic chemistry, and molecular and cellular biology.
Towards the goal of isolating cell targeting ligands, our laboratory has developed phage display panning protocols to identify peptides that mediate binding and uptake into cells. A remarkable feature of the peptides selected using this panning procedure is their cell-specificity. In other words, selected peptides show specificity for the cell type they were selected against when compared to another cell type. The high discriminating power of the selected phage allows us to selectively target different cell types, even those of similar types or classifications. The approach employs an unbiased screen in which there is no selective pressure towards binding a particular macromolecule. This has the important advantage that it requires no prior knowledge of the cellular receptor.
Thus, we can isolate targeting peptides for cell types for which little is known about their cellular landscape or whose cellular landscape may change over time with varying conditions. Furthermore, it allows for the discovery of cell surface macromolecules that may not have been considered as viable targets or have not yet been identified. We are currently focused on the isolation of cell-targeting reagents for 4 general classes of cells; lung cancer tumors, blood derived cancers lymphoma and leukemia, cells of the immune system, and β-cells of the islets of Langerhans. The goals and challenges differ for each class of cells. More information about each project can by clicking on the links below or in our recent publications.
- Isolation and Utilization of Cell Specific Reagents for Lung Tumors
- Targeting Critical Cells of the Immune System
- Development of Novel Ligands for the Diagnosis and Treatment of Blood Derived Cancers
- Peptide-Mediated Targeting of the Islets of Langerhans
- Identification of the Receptor(s) Responsible for the Binding and Uptake of the Selected Peptides