David Lawrence works to understand the biochemical processes of the cell by studying them as they happen in the cell as opposed to studying them in vitro. He currently focuses on applying his discoveries to cancer detection and treatment and, to a more limited extent, inflammatory diseases. Lawrence is a Fred Eshelman Distinguished Professor of Medicinal Chemistry and holds joint appointments in the Department of Chemistry and the Department of Pharmacology and is a member of the UNC Lineberger Comprehensive Cancer Center. Before joining the School in 2007, Lawrence spent eleven years as a professor of biochemistry at the Albert Einstein College of Medicine at Yeshiva University in New York. Before that, he was at the State University of New York at Buffalo for ten years.
The Lawrence research program encompasses the fields of organic and peptide synthesis, photochemistry, enzymology, molecular and cell biology, and microscopy. Across these fields, the Lawrence lab conducts the synthesis, characterization and cell-based application of light-responsive agents (inhibitors, sensors, activators, proteins and gene expression system), which are designed to manipulate and probe the biochemical pathways that control cell behavior. Disease states under investigation include cancer, disorders of metabolism, and inflammatory diseases.
Optogenetics is a powerful light-triggered technology that, via control of biochemical activity, enables spatiotemporal manipulation of cellular and organismal behavior. Neurobiologists, who have been the chief end-users of this technology, have inserted light-gated ion channels (obtained from lower organisms) into the nervous system of higher organisms, including mammals. In addition to exogenous light-gated ion channels, cell and molecular biologists have turned their attention toward the construction of light-responsive analogs of endogenous mammalian proteins. We have developed a straightforward strategy that overcomes the challenges associated with the preparation of optogenetic proteins and have employed these engineered species to explore the relationships between compartmentalized signaling activity and cell behavior.
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.
Design and Application of Photoresponsive Modules in Circulating Erythrocytes.
Spatiotemporal Control of Migratory Cellular Behavior
Profiling Signaling Activity and Gene Expression in Single, Pancreatic Adenocarcinoma Cells Using CE-RNA-Seq
Towards Glucose Transporter-Mediated Glucose-Responsive Insulin Delivery with Fast Response
Creation of a Suite of XR Experiences in Laboratory Safety
Photothrombolytics: Illuminating a Safe and Efficacious Thrombolytic Therapy
A Light Shield for Protecting Sensitive Organs Against Cytotoxic Therapeutics
1976 B.S. in Biological Sciences, University of California at Irvine
1982 Ph.D. in Organic Synthesis, University of California at Los Angeles
Research Director: Professor Robert V. Stevens
1982 to 1985, NIH Postdoctoral Fellow in Bio-Organic Chemistry, The Rockefeller University
Research Director: Professor E. Thomas Kaiser