My research program focuses on understanding the deterioration of oral health commonly associated with human immunodeficiency and simian immunodeficiency virus (HIV/SIV) infection. In particular, we are identifying the molecular mechanisms that lead to oral pathogenesis and development of opportunistic secondary infections. Secondary oral infections in HIV patients, and oral disease in general are increasingly recognized as polymicrobial perturbations to the delicately balanced ecosystem of the oral biofilm, or microbiome. We want to characterize alterations in the oral microbiome that are linked to disruption of host epithelial immune function, and correlate with the appearance of oral complications or clinical stages of disease progression. To accomplish these goals, we are conducting clinical studies with a well established and expanding cohort of HIV infected patients, balanced with basic science research using the non-human primate SIV model. We utilize cutting-edge next-generation sequencing, high throughput gene expression analysis, and in vitro tissue engineering technologies to comprehensively unravel the complexities of host-microbe interaction.
Dandekar S, George MD, Bäumler AJ. 2010. Th17 cells, HIV and the gut mucosal barrier. Curr Opin HIV AIDS. 5(2):173-8.
George MD, Verhoeven D, Sankaran S, Glavan T, Reay E, Dandekar S. 2009. Heightened cytotoxic responses and impaired biogenesis contribute to early pathogenesis in the oral mucosa of simian immunodeficiency virus-infected rhesus macaques. Clin Vaccine Immunol. 16(2):277-81.
George MD, Verhoeven D, Sankaran S, Dang AT, Dandekar S. 2008. Loss of growth factor receptor signaling in the oral mucosa during primary SIV infection may enhance apoptosis and promote pathogenesis. J Med Primatol. (37) Suppl 2:55-61.
George MD, Wehkamp J, Kays RJ, Leutenegger CM, Sabir S, Grishina I, Dandekar S, Bevins CL. 2008. In vivo gene expression profiling of human intestinal epithelial cells: analysis by laser microdissection of formalin fixed tissues. BMC Genomics. 9(1):209.
Sankaran S, George MD, Reay E, Guadalupe M, Flamm J, Prindiville T, Dandekar S. 2008. Rapid onset of intestinal epithelial barrier dysfunction in primary HIV infection is driven by imbalance between immune response and mucosal repair and regeneration. J Virol. 82(1):538-45
Raffatellu M, Santos RL, Verhoeven DE, George MD, Wilson RP, Winter SE, Godinez I, Sankaran S, Paixao TA, Gordon MA, Kolls JK, Dandekar S, and Baumler AJ. 2008. Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nature Medicine 14(4):421-428.