Ghosh Lab
Principal Investigator: Partho Ghosh
Institution: University of California San Diego (La Jolla, CA)
Primary Subfield: Immunology
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
Streptococcus pyogenes (Strep A) is a major global pathogen responsible for significant morbidity and mortality. Efforts to develop a broadly protective immunization strategy against Strep A have been hindered by the extensive sequence variability of its primary virulence factor, the M protein, with over 220 known M types. The immune response to M proteins is typically type-specific, limiting broad protection. This project builds on recent structural and functional discoveries to design M protein-based immunogens that elicit cross-reactive antibodies against diverse Strep A strains. We hypothesize that conserved 3D structural patterns in M proteins can drive broad immune recognition and be leveraged to enhance immunogen design. A promising M protein-based immunogen that completed Phase I trials, StreptAnova, generates cross-reactive antibodies, yet the basis for this cross-reactivity is unknown. Our work suggests that the M type cross-reactivity may be due to conserved three-dimensional (3D) structural patterns within M proteins that mediate binding to human C4b-binding protein (C4BP), an essential virulence factor. Notably, half of the M proteins in StreptAnova contain a C4BP-bind…
Active NIH Awards
- 1R01AI189749-01A1: Antibody Interactions with M and M-like Proteins (2026)
- 5R01AI154149-05: Evasion of host immunity by the M protein (2024)
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