Dr. Sanjay Ram’s lab focuses on complement evasion mechanisms of the pathogenic Neisseriae – Neisseria gonorrhoeae (the gonococcus) and N. meningitidis (the meningococcus). Gonococci scavenge sialic acid (a 9-carbon sugar) from the host and add this molecule to their lipooligosaccharide (LOS). Sialylation of LOS renders gonococci resistant to killing by complement, in part by enhancing the binding of a complement inhibitor called factor H (FH) to the bacterial surface. Meningococci also recruit FH from their human hosts, which enable them to escape complement. One of the ligands for FH on meningococci is a lipoprotein called FH-binding protein (FHbp) that currently is a key component of two group B meningococcal vaccines recently licensed in the U.S. The current focus of the lab is to use the knowledge gained pertaining to complement evasion mechanisms to design novel therapies against rapidly emerging multidrug-resistant N. gonorrhoeae, a major global public health concern. Examples include the use of chimeric FH-Fc fusion molecules that activate complement and enhance phagocytosis, and the use of analogs of sialic acid that that “compete out” the protective role physiological sialic acid plays on the bacterial surface. These approaches may be useful against several other medically relevant pathogens that utilize sialic acid and/or FH to subvert host defenses. Another ongoing project aims to define the basis for increased gonococcal transmission and burden of infection in women with pre-existing chlamydia co-infection. Dr. Ram serves as an attending on the Infectious Diseases Consult Service at UMass.
Sanjay Ram, MBBS