Development of fluorescent peptide probes to assess kinase activity in Non-Hodgkin's Lymphoma and identify potential therapeutic targets

 

Trainee:

Marissa Cann

cann

Research Mentor:

David Lawrence

lawrence

Clinical Co-mentor:

Kristy Richards

richards
Home Department Pharmacology
Project Description My thesis project will involve the development of a capillary electrophoresis/laser-induced fluorescence (CE-LIF) detection method to assess the behavior of crucial members of the kinome in Non-Hodgkin’s Lymphoma (NHL). The probes will be fluorescently-labeled peptide substrates that are selective for various kinases important in NHL progression, such as the Src-family kinases Lyn, Fyn, and Lck. By tailoring the peptides to be cell-permeable and degradation-resistant, they can be readily applied to primary cells and thus applicable to patient samples. The CE-LIF method will allow us to assess the aggressiveness of a patient’s disease and identify specific therapeutic targets for each patient, thereby providing clinicians with treatment plan options that can be rapidly commenced. Furthermore, the peptide probes will also be usable in the Deep Quench assay developed by our lab, in which enzymatic activity is reported by a real-time fluorescent readout. By developing a probe compatible with Deep Quench, we will be able to study the real-time activity of kinases in their native environment within live cells. In addition, these kinase-sensing probes could also be applied to assess the efficacy of potential anti-cancer therapeutic drugs.