My laboratory is interested in discovering new ways to treat cancer and infectious diseases. There are two main projects in the lab.

The first project is aimed at finding new targets for drug discovery. In the traditional drug discovery process, researchers select a target and then attempt to find appropriate drugs to attack the target. We take a chemical genomic approach using a novel molecular biology method called SICLOPPS (Scott, et al., PNAS (1999) 96:13638-43) to pinpoint the most sensitive targets in diseased cells. Collections of diseased cells are given genetic instructions to make molecules in such a way that each cell gets a different set of instructions. The approach is a bit like a lottery: cells that get instructions to make molecules that cure the disease, or selectively kill cells carrying it, can be identified using powerful genetic selection and screening methods that we develop in the laboratory. Molecular "hits" that emerge from the selection/screening process are produced and studied in detail to determine the physiological target and understand how the hit molecule modulates the target's biochemical function. The end result is identification of the best targets for drug development, and molecules that can serve as lead compounds or even drugs.

The second project is focused on drug resistance in breast cancer. Breast cancer is among the most commonly diagnosed cancers, and many breast cancer patients have an excellent prognosis for long-term survival. However, some breast cancer patients respond poorly to chemotherapy, and long-term disease-free survival among these patients is rare. Sadly, drug-resistant forms of breast cancer disproportionately strike the youngest patients. We have discovered a potential basis for the difference between treatable and many drug-resistant breast cancers. We are currently trying to exploit this difference to develop drugs that convert resistant cancers into more treatable forms in hopes of prolonging disease-free survival rates for patients with otherwise untreatable forms of breast cancer.

biochemistry; biophysics; molecular biology; enzymology; virology; host-pathogen interaction; drug discovery; target discovery; chemical genomics; chemical genetics; chemical biology; intein; combinatorial library; high-throughput screening; small molecule; cyclic peptide; protein engineering; protein-protein interaction; breast cancer