The Kaushic Lab focuses mainly on understanding host-pathogen interactions within the female genital tract. We are interested in innate and mucosal immunity against the STIs. We focus on key factors such as sex hormones, co-infections, microbiome in the local microenvironment of the reproductive tract to understand how they affect the interactions with sexually transmitted viruses, HIV-1 and HSV-2, to determine the outcome of exposure. The lab has a variety of clinical and basic projects that involve in vivo mouse modeling, clinical samples as well as in vitro primary cultures and cell lines. The overall goal is to develop prophylactic strategies prevent sexually transmitted infections in women. Currently, the laboratory is funded by three CIHR projects and an OHTN Applied HIV Chair to Dr. Kaushic.
1.CIHR Operating Grant: Understanding the role of mucosal epithelial barrier functions in HIV-1 pathogenesis
In this grant we are conducting projects to understand the cellular mechanism of barrier disruption and protection against HIV-1, as well as to translate the results from our primary epithelial cultures into a humanized mouse model of HIV-1 infection. We are examining, in vivo, the mechanism of HIV-1 induced barrier disruption and immune activation with the goal of testing if HIV-1 infection can be prevented by protecting mucosal barrier in the genital tract.
2. CIHR Operating Grant: Mechanism of female sex hormone regulation of susceptibility and immune responses to sexually transmitted viruses
In this grant we are focusing on three areas that will our understanding of how sex hormones affect susceptibility and anti-viral responses. Specifically we are determining the mechanism by which E2 induces Th17 responses in the reproductive tract and influences anti-viral immunity, examining the involvement of TNF-a in P4 treatment related immunopathology and exploring the differential effects and the mechanism(s) by which P4 and different progestins influence anti-viral immune responses.
3. CIHR HIV Mucosal Team Grant: Interaction between sex hormones, microbiome and innate immunity in the female reproductive tract: Impact on mucosal immune responses and susceptibility to HIV
This Team Grant is centered on two themes. The first tests the premise that progesterone treatment leads to detrimental changes in microbiome, innate immunity and T cells leading to increased HIV infection. The second tests whether manipulation of genital microenvironment, either by enhancing local estrogen levels or adding probiotics will decrease innate inflammation and activated mucosal T cells, and consequently decrease HIV susceptibility. Clinical, animal model, in vitro and transcriptomic studies are being conducted to generate a combination of observational and mechanistic data to confirm the hypothesis. These studies will provide for the first time a comprehensive understanding of the cause-effect relationship between hormonal environment, microbiome and its effect on HIV susceptibility and mucosal immunity.