Genomic DNA is wound around histone proteins in order to condense and compact this long string of information. These histone proteins are acetylated, deacetylated, methylated, demethylated, phosphoralated, and dephosphorolated by various enzymes. The crystal structure and its active site of LSD1, a lysine specific demethylase, are shown in the figure. Our research focuses on the mechanism of this enzyme and other enzymes that modify histones. Modifications of histones can control the expression of certain genes and thus has been implicated in various cancers. Clinical trials are being undertaken to study the effects of certain HDAC (histone deacetylase) inhibitors in cancer therapy.

Resistant strains of Staph. aureus (MRSA) and Enterococcus faecim (VRE) have become a serious threat to our health care system. These and other resistant bacteria may soon become untreatable infections by becoming resistant to our current antimicrobial arsenal. Our lab is currently involved in three areas of antibiotic research. We use synthetic organic techniques to develop new antibiotics and to increase the bioavailability of known antibiotics. The x-ray crystal structure of the lipodepsipeptide antibiotic ramoplanin was recently solved in this laboratory. ( Ramoplanin Movie for Quicktime and Ramoplanin Movie for Windows.) We also use molecular biology and biochemistry techniques to research known gene clusters that are involved in the biosynthesis of nonribosomal peptides and polyketides. Lastly, we have been studying an important enzyme ( Sortase A - see Sortase A and B movie) that is involved in the anchoring of proteins to the outer membrane of gram-positive bacteria.

The ability of the gastrointestinal tract to recognize beneficial microbes from harmful microbes is an important step toward fighting infection and remaining healthy. Recent studies have indicated that there are over 500 species of microbes residing in the human gut. The innate immune system detects microbe-associated pattern molecules (MAPM) using pattern-recognition molecules. One such molecule is the NOD2 protein. Mutations in NOD2 have been implicated in inflammatory bowel disease and Crohn's disease. Our lab is researching the interaction of the NOD2 protein with several different synthetic MAPM in order to develop a novel therapeutic for Crohn's disease.