Research & Activities:
I have a longstanding interest in the conformations of nucleic acids and the ways in which they interact with other molecules (both proteins and low-molecular-weight ligands). This has led to publications on the fast kinetics of ligand binding, the conformation of nucleic acids as influenced by other macromolecules (including compaction to the "psi" state) and a structural model for the covalent complex between benzo[a]pyrene diol epoxide and DNA. My students and I have demonstrated the DNA-conformation-modulating properties of small, acid-soluble spore proteins (SASPs) from Gram-positive bacteria.
The interest in DNA-binding proteins has led me to work on nuclear receptors and we have published homology-extension models of the human estrogen receptor as well as the related vitamin D receptor. I also have supervised the synthesis of a number of potential photodynamic therapy agents targeted to the estrogen, androgen and vitamin D receptors. This work is ongoing.
In the last three years I have reoriented most of my research interests towards bioinformatics in collaboration with Professor Temple F. Smith of the Boston University Department of Biomedical Engineering. In addition to the homology modeling described above, I have pursued questions regarding the overall layout of chromosomal DNA as revealed by strand asymmetry in base composition and gene locations and I have created a functional database of mitochondrial proteins for yeast (C. cerevisiae). This work involves dissecting genes into their constituent protein domains, constructing phylogenetic trees for these domains, and identifying "missing" genes which are required for mitochondrial function, but not yet annotated in the database(s). We have employed prior-based profiles to identify more than 2000 homologs for ca. 415 mitoproteins, and the phylogenetic trees constructed with these homologs serve to define the evolutionary origins of the yeast mitochondrial "proteome."
I am also collaborating with Dr. Joel Graber and Professor Charles Cantor in informatic analysis of the 3'-end-processing (cleavage and polyadenylation) sites in eukaryotic mRNAs.
I currently direct a Chemistry Graduate Student (Taner Kaya) and I codirect several Pharmacology and Engineering graduate students (with T. Smith). Further description of my active research in bioinformatics, including a list of recent publications, is described at the home of the BioMolecular Engineering Research Center.