• 1983: B.S., Biophysics, Second Moscow Medical Institute, Medico-Biological Department, Moscow, Russia
• 1990: Ph.D., Institute for Transplantation and Artificial Organs, Moscow, Russia
• 1990 – 1994: Laboratory of Organ Preservation, Institute for Transplantation and Artificial Organs, Moscow, Russia
• 2000 – 2002: Postdoctoral Fellow, Department of Microbiology and Immunology, Uniformed Services University of Health Science, Bethesda, MD. Sponsor: Stefanie N. Vogel

• 2002 – present: Research Associate; promoted to Assistant Professor, Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD.

My research is centered on the protein-protein interactions underlying TLR signal transduction. The TLRs (Toll-like receptors) sense conserved microbial molecules to induce the host response to infection. Structurally, the TLRs are type I receptors composed of an N-terminal ectodomain, a transmembrane helix, and a cytoplasmic region formed by a Toll-Interleukin-1 Resistance (TIR) domain (Figure 1).

The common mechanism of signaling through the type I receptors is that the interaction of an agonist with the extracellular domain either induces the formation of a receptor dimer, or changes the conformation of a preexisting dimer (discussion on which scenario is applicable to the TLRs is still continues in literature) in such a way that it allows two intracellular TIR domains to interact physically. This simple rearrangement serves as a nucleating act for the recruitment of adapter proteins that also have TIR domains. These processes result in formation of a large multiprotein complex, or “signaling platform”, that function to propagate the signal downstream, ultimately resulting in the change of expression of several hundred “primary immune response” genes. The architecture of the TLR signaling complexes, however, is poorly understood at this time largely due to lack of reliable methods to study such interactions due to the inherent weakness of individual interprotein interactions in transitory complexes.

The aim of my current research is to understand the feasibility of identifying protein-protein interfaces, the complementary areas on surfaces of two interacting proteins, by ‘decoy peptide’ approach. A decoy peptide is a continuous segment of primary sequence of a domain that forms a non-fragmented patch on the domain’s surface. Such decoys combined with a vector polypeptide are often capable of inhibiting the function mediated by decoy’s prototype protein due to their ability to bind the docking site on the protein that interacts with the decoy’s prototype. We create a series of decoys that collectively represent entire surface of an interaction domain (Figure 2) and test each decoy for the ability to inhibit the function of decoy’s prototype. Applying this strategy to a number of domains that mediate TLR signaling, we seek to understand if this approach accurately identifies protein-protein interfaces.