My research brings together biology, chemistry and physics to provide a quantitative description of protein interactions. Pointillistic super-resolution imaging techniques can be used to elucidate nano-scale spatial organization of proteins and investigate biological processes that are critical to the progression of cancer and other human diseases. To advance drug discovery, we use Photoactivated Localization Microscopy with pair-correlation analysis (PC-PALM), a quantitative fluorescence imaging method with high spatial resolution and single-molecule sensitivity. This technique allows us to obtain information about a wide range of spatial scales from approximately 10 nm to 1 mm, along which many remodeling events take place. Our research interests lie in the advancement of quantitative nano-scale methods to study important biological mechanisms and in the development of novel therapeutic and imaging agents with these powerful techniques.
1. Pointillistic Microscopy: Investigation of Protein Signaling
Elucidation of protein organization in the plasma membrane will clarify the mechanisms of signaling networks that regulate cellular function and communication. Quantitative super-resolution microscopy techniques are used in our lab to investigate the distribution of plasma membrane receptors such as growth factor receptors and G protein-coupled receptors (GPCRs) in the steady state and upon perturbation with various ligands. Monoclonal antibodies (mAbs) are the focus of both basic research and translational medicine due to their exquisite specificity and high affinity. We have an ongoing collaboration with Professors Williams, Horne and Park at City of Hope to arm antibodies to detect disease, treat disease, and elucidate the basic biology of antigen signaling. Over the long-term we envision that advanced super-resolution microscopy methods such as PC-PALM can be used as a tool for quantitative, high-throughput screening of ligands and their receptors on the cell membrane to develop novel cancer therapeutics that are specific to the disease site.
2. Nano-scale Investigation of the Nuclear Pore Complex machinery
Proteinaceous assemblies called nuclear pore complexes (NPCs) mediate transport of macromolecules across the nuclear envelope. NPCs are selective for the passage of certain molecules, yet provide high throughput in order to maintain proper cellular order and function.
Individual nucleoporins have unique roles in regulation of nucleocytoplasmic transport, and their defects can often lead to various disease phenotypes including cancer. We aim to elucidate the mechanistic contributions of the specific nucleoporins during both normal cell function and carcinogenesis by utilizing and developing nano-biological assays and biophysical tools such as super-resolution microscopy. In addition, we are interested in exploring the effect of potential anticancer agents on the NPC machinery. Mechanisms that regulate nucleocytoplasmic transport of proteins may ultimately provide novel targets and opportunities for drug development.