David S. Lawrence, Ph.D.

Conventional strategies for identifying the biochemical basis of tumorigenesis and metastasis rely upon the search for up- (or down-) regulated genes and proteins. However, the complexity and heterogeneity of many forms of cancer make it clear that this approach alone is not sufficient for extracting the information necessary to generate diagnostic and prognostic biomarkers. This biomedical imperative dictates the development of a series of new cellular and molecular strategies to tackle, what is admittedly, a devilishly difficult problem. We’ve developed an array of fluorescent sensors of protein remodeling enzymes (kinases, phosphatases, demininases, proteases) that furnish robust readouts of catalytic activity (>100 fold) across the visible spectrum and into the near infrared. We’ve employed multicolor sensing of catalytic activity to identify aberrant tyrosine kinase activity in drug resistant cells, identified a key protein kinase responsible for promoting the transition from prophase to metaphase, and demonstrated that the proteasome’s three protease activities constitute a characteristic “catalytic signature” that varies as a function of species, cell type, and disease. Sensors have been used to correlate signaling activity with prostate cancer invasiveness, distinguish between signaling activity in the individual compartments of organelles, monitor allosteric crosstalk between active sites within multi-subunit complexes, and visualize epigenetic enzymatic activity.

Light-triggered drug delivery furnishes spatial and temporal control and offers the possibility of precision dosing and orthogonal communication with different therapeutic agents. These inherent attributes of light have been advocated as advantageous for the delivery and/or activation of drugs at diseased sites for a variety of indications. However, the tissue penetrance of light is profoundly wavelength dependent. We’ve developed a phototherapeutic platform that responds to wavelengths within the optical window of tissue (600 – 900 nm) and has been employed to deliver small molecule, peptide, and protein therapeutics.

Virtual reality experiences have been developed to introduce students to key concepts in laboratory safety. The latter, as well as ongoing work with the American Chemical Society, have been instituted in response to the recognition that a lecture setting fails to convey the sensory experience of a laboratory environment.