UCLA Ph.D., (1982), NIH Postdoctoral Fellow, The Rockefeller University, 1982 - 85. Assistant, Associate, and Full Professor of Chemistry, SUNY Buffalo (1985 - 95). Professor of Biochemistry, The Albert Einstein College of Medicine (1996 - 2007). Professor of Chemistry, Medicinal Chemistry & Natural Products, and Pharmacology, Member, Lineberger Cancer Center (2007 - present)
Living cells have been referred to as the test tubes of the 21st century. The design and synthesis of molecules that inhibit, probe, or alter the biochemistry of the cell lies at the nexus between chemistry and biology. The field of Chemical Biology seeks to correlate the underlying chemistry of life with the behavior of cells, tissues, and organisms. By revealing the nature of the molecular engine that drives cellular behavior Chemical Biology provides the molecular foundation upon which innovative therapies can be created for the entire spectrum of human afflictions. The projects underway in the Lawrence Lab have biological implications, particularly in the area of cancer detection and treatment. Organic synthesis, solid phase peptide synthesis, and photochemistry all play a key role in the creation of the compounds under study.
Inhibitors and Drug Development
We have developed a combinatorial library strategy that creates extraordinarily potent and selective inhibitors for specific signaling proteins. We have constructed compounds that activate the insulin pathway (diabetes), the leptin pathway (obesity) (Endocrinology, 2007, 148, 433-40) and inhibit various cancer-causing pathways (Biochemistry, 2008, 47, 986-96; J. Amer. Chem. Soc. 2009, 131, 13072 - 3; ChemBioChem, 2008, 9, 507-9).
We have synthesized fluorescent sensors that allow us to visualize intracellular enzymatic activity, including biochemical behavior responsible for division (Chem. & Biol., 2007, 14, 1254-60), digestion of old and ineffective proteins (J. Amer. Chem. Soc., 2010, 132, in press), and uncontrolled cell growth (J. Amer. Chem. Soc., 2007, 129, 2742-3).
In collaboration with Professor Nancy Allbritton, we are developing an array of sensors that will be used to detect breast, pancreatic, and prostate cancer.
Light-Activated Inhibitors, Sensors, and Signaling Proteins
An array of compounds have been prepared that undergo dramatic chemical changes in response to light (ACS Chemical Biology 2009, 4, 409-27). These light sensitive agents can be switched on or off at any time or place inside living cells, thereby allowing the chemistry of the cell to be controlled wherever and whenever we so desire. Issues currently under study include identifying the role that key proteins play in controlling the stages of cell division, motility, and death. Examples include light-controlled proteins (Science, 2004, 303, 743-6), inhibitors (Organic Lett., 2007, 9, 2249-52), and sensors (J. Amer. Chem. Soc., 2006, 128, 14016-7; J. Amer. Chem. Soc., 2010, 132, in press).
Light-Induced Gene Expression
A strategy has been developed for using light to activate the expression of any gene of interest. This furnishes a direct means to examine the biological consequences of gene expression within the context of specific tissue microenvironments. This technology is being applied to living animals in collaboration with a group at the Albert Einstein College of Medicine (J. Biomed. Optics 2005, 10, 0514061 -9).