The research in our laboratory is aimed at the structural characterization of the molecular mechanisms underlying cell-cell interactions and signal transduction across the cell membrane. Specifically, we use X-ray crystallography and cryo-EM, combined with other biophysical and biochemical techniques, to study the interactions of cell-surface receptors with extracellular ligands, as well as the subsequent initiation of downstream signaling. Some of the ligand/receptor signaling systems that we study include ephrins/Eph receptors, netrins/DCC/Unc5, and angiopoietins/Ties. We are also interested in the role of the ADAM family of cell surface metalloproteases in regulating signaling across membranes. Recently, we have been working towards the development of novel Eph and ADAM inhibitors as anti-cancer and anti-neurodegenerative disease agents. Of particular interest are monoclonal antibodies targeting the substrate-recognition regions of ADAMs or the ligand-binding domains of Eph receptors.
Figure 1 Structure of the Netrin-1/Neogenin complex.
- Structural studies of ADAM metalloproteases
- Structural studies of Eph receptors
- Development of conformation-specific therapeutic antibodies
Dimitar Nikolov carried out his undergraduate studies in physics and biology at the University of Sofia in Sofia, Bulgaria from 1991 to 1996, receiving B.S and M.S. degrees. He received his Ph.D. in Molecular Biophysics from The Rockefeller University in New York City in 1996 and joined the faculty of The Memorial Sloan-Kettering Cancer Center and Weill Cornell the same year.