The Kaushic Lab focuses on understanding host-pathogen interactions within the female genital tract, particularly innate and mucosal immunity against sexually transmitted infections (STIs). We investigate key factors such as sex hormones, co-infections, and the vaginal microbiome to understand how these affect infection and outcomes of sexually transmitted viruses HIV-1 and HSV-2. The lab has a variety of clinical and basic science research projects which involve in vivo mouse modelling, clinical sampling, as well as in vitro primary cultures and cell lines. By better understanding interactions between the vaginal environment and STIs, such knowledge can be implemented towards development of prophylactic strategies to prevent STIs in women. Currently, the laboratory is funded by a CIHR Scientific Director grant awarded to Dr. Kaushic.
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IN VITRO & EX VIVO
The Kaushic Lab performs in vitro experiments using VK2/E6E7 cells and ex vivo experiments using primary genital epithelial cells that we isolate from human tissues. We often grow these cells in transwells and supplement the basolateral or apical medium with different factors to elucidate their effect on the epithelial cells we grow. Some factors that our lab investigates includes different compositions of vaginal bacteria , sex hormones, and STIs. We then try to understand what effects these factors have on the vaginal epithelial cells to determine if susceptibility to pathogens may be affected by these factors.
Ongoing Project: Understanding the Role of the Vaginal Microbiome in Female Reproductive Health
The female genital tract is colonized by an endogenous vaginal microbiome that has been shown to influences epithelial barrier integrity. A vaginal microbiome dominated by Lactobacillus species, termed a eubiotic vaginal microbiome, is associated with protection against adverse urogenital outcomes and lower levels of inflammation. A dysbiotic vaginal microbiome has higher diversity of bacterial species and is highly correlated with many adverse reproductive outcomes. It is critically needed to understand how the complex interactions between factors found in eubiotic and dysbiotic states, such as bacterial metabolites and the bacterial biofilms, affect the epithelial barrier in order to understand the differences in health outcomes associated with each state.
Ongoing Project: Understanding the Interactions Between Different Human Immunodeficiency virus (HIV) Strains and the Vaginal Epithelial Barrier
Majority of HIV-1 transmission occurs in women through heterosexual intercourse and female genital tract is the primary portal of entry. Although both CCR5-tropic (R5) and CXCR4-tropic (X4) HIV-1 strains are present in semen, transmission occurs predominantly through R5. The mechanism underlying this preferential selection of R5 during transmission is not completely understood. In this study we examined the interactions between X4 and R5 strains of HIV-1 with genital epithelial cells to gain a better understanding underlying the preferential selection of R5 strains for mucosal transmission.
The Kaushic Lab also performs research using mouse models, as this allows us to investigate the complex and dynamic interactions between physiology and environmental factors, as well as how these interactions may affect susceptibility to pathogens.
Ongoing Project: Colonizing Mice with Human Vaginal Microbiota to Investigate its Role on Pathogen Susceptibility
The objective of this project is to develop in vivo mouse models that harbour human vaginal bacteria, both eubiotic-containing Lactobacillus crispatus and dysbiotic-containing Gardnerella vaginalis. Mice do not normally have these bacteria in their vaginal microbiome, which is why we need to develop these models. These models can be used to study the effect eubiotic and dysbiotic bacteria have on outcomes related to HSV-2 infection, with the hypothesis that Lactobacillus species will be protective and Gardnerella vaginalis will be unprotective.
We are able to implement the work we do in vitro and in vivo to develop translational and clinical studies. These studies allow us to have a real-life impact on women's reproductive health and make an impact on a community level.
Ongoing Projects: Improving Vaginal Health to Decrease Biological Risk of HIV-1 Infection in Canadian African/Caribbean/Black (ACB) Women
We are currently working on a prospective, randomized, open-label, phase I intervention study where we administered low dose intravaginal estrogen and/or Lactobacillus-based probiotics to premenopausal ACB women for 30 days. Our goal is to determine if these interventions can improve vaginal health and risk of STI acquisition by enhancing Lactobacillus abundance in the vaginal microbiome, reducing cervicovaginal inflammation and diminishing the presence of HIV target cells.