While at the Keck Center, Vishwanatha studied Group A streptococcus (GAS). GAS is a human specific pathogen which causes trivial infections e.g., sore throat and impetigo, as well lethal infections e.g., necrotizing fasciitis and rheumatic heart disease. In order to infect its host, GAS expresses several pathogenic proteins like streptokinase (SK) which is secreted to the surrounding environment and M or M-like proteins which are embedded on cell membrane. M or M-like proteins are used as a basis for serotyping GAS strains into >250 types. GAS uses these proteins to exploit functional host fibrinolytic system for their own advantage. M or M-like proteins (e.g. M1 and PAM, respectively) tightly bind human plasminogen (hPg) and fibrinogen. SK secreted by GAS non-proteolytically activates hPg to a broad spectrum serine protease, plasmin (hPm), localizing proteolytic activity of hPm to GAS surface. hPm can break tissue barriers and assists GAS to invade tissue barriers and disseminate into deeper tissues.
His research interests included studying the biological consequences of altering M or M-like proteins and SK on HPg activation and their effect on GAS virulence. Additionally, he also studied structural differences in hPg binding domain within PAM. PAM binds to kringle2 of hPg with high affinity and the binding mechanism has been characterized. However, prevalence of amino acid sequence variation among several PAMs within the hPg binding region without affecting their binding to hPg warrants further studies.
His final thesis titled “Sequence Diversity in Streptokinase and M-Proteins, Their Co-Inheritance and Functional Relationships in Group A Streptococcal Virulence”.
Dr. Chandrahas received the position of Postdoctoral Fellow at Sanford Burnham Prebys Medical Discovery Institute, LaJolla, California after graduation.
Shailaja has performed research in the field of neuroscience utilizing integrated biophysical and biochemical techniques to study the interaction of peptides known as conantokins and their target ion channel receptors, NMDAR. Conantokins are peptides, produced by snails inhabiting the Indo-Pacific Ocean. Conserved distribution of post-translationally modified amino acid residues, γ-carboxyglutamate, provide the peptides with unique structural and functional properties that can be exploited for rational drug design towards NMDAR-elicited excitoxicity events in pain, such as in Parkinson’s disease.
Her final thesis titled “Structure and Functional Relationships of N-Methyl-D Aspartate-Receptor Specific Antagonistic Peptides from the Conus Species of Marine Snails”.
Dr. Kunda received the position of Postdoctoral Fellow at Tata Institute of Fundamental Research, Mombai, India after graduation.