Inflammation is an extremely refined biological response that involves intercellular communication networks and intracellular signaling pathways mediated predominantly by transient protein-protein/peptide interactions (PPI). A systematic survey estimated that 15-40% of all interactions in the cell are mediated through protein-peptide interactions suggesting that most macromolecular complexes are affected either directly or indirectly by peptide-binding events. The protein interface is predefined and ready to accommodate the binding peptide. The peptide ‘‘scans’’ the protein surface in an efficient way. The essence of their function is embodied in the linear amino acid sequence and is independent of tertiary structure. Most of the energy in peptide binding is due to the binding of core hot spot residues. Low affinity interactions between proteins and short solvent exposed proline rich peptide sequences within their binding partners play an essential role in intracellular signaling. Since alterations in PPI cause, accelerate and precipitate chronic inflammatory diseases, control or inhibition of known interactions represents a prime target for drug discovery.
Research in Dr. Srinivasan’s is similar to drug discovery and development. The focus is targeting PPI critical for perpetuating neuro-inflammatory responses using rationally designed peptide therapeutics. Significant contributions include design and development of CD80-competitive antagonists to suppress T cell activation in Th1 or pro-inflammatory autoimmune diseases and GILZ analogs that target the pro-inflammatory subunit of nuclear factor-kappa B, the master regulator of inflammatory responses. The efficacy of the peptide agents have been validated in models of multiple sclerosis and Alzheimer’s disease. To fully execute the development of the candidate peptide drugs, the research in Dr. Srinivasan’s lab formed the basis of a collaborative start-up initiative between the Provaidya LLC and the Indiana University Research Technology Corporation (www.provaidya.org ).
List of recent publications in PUBMED
Salivary research
Human saliva is a complex mixture composed of secretions from three major salivary glands and numerous minor salivary glands contaminated with serum constituents, blood corpuscles, exfoliated oral epithelial cells and a plethora of microorganisms. Over the last decade, saliva has gained considerable importance as a diagnostic fluid for predicting populations at risk for a variety of oral and systemic conditions. The clinical significance of salivary proteome, transcriptome and genetic markers have been explored for cancers of the oral cavity, breast and pancreas, for infectious diseases including hepatitis and acquired immune deficiency syndrome and for metabolic diseases such as diabetes and osteoporosis. Research by Dr. Srinivasan’s group investigates the value of analytes in clarified saliva as biomarkers of periodontal and systemic diseases. Additional interest includes evaluation of the potential use of epithelial cells in saliva as tools to investigate the host-microbial interactions.
List of recent publications in PUBMED
List of recent publications in PUBMED