Squamous metaplasia and emerging neoplasia are best illustrated at the transition zone (TZ) of the squamous epithelium of the ectocervix and columnar epithelium lining the endocervix of the female reproductive tract. Cervical cancer is the fourth most common cancer in women worldwide, and nearly 90% emerge from squamous metaplastic cells at the TZ. Squamous metaplasia, a precancer lowgrade dysplastic condition, appears as islands in the columnar cripts of the female reproductive tract, which eventually culminates into a total replacement of columnar epithelium by squamous epithelium. Despite the overwhelming pathological importance of squamous metaplasia in carcinogenesis, several critical questions about their increased susceptibility to persistent infections and carcinogenesis remain unanswered. In particular, the insights into mechanisms underlying TZ microenvironment reprogramming during squamous metaplasia and subsequent neoplasia development. We aim to identify how the TZ microenvironment evolves during squamous metaplasia development influenced by extrinsic factors such as diet and how it facilitates infections and carcinogenesis. 

High-risk human papillomavirus (HPV) infections are recognized as key etiological agents of uterine cervical cancers. However, only a very minute fraction of women persistently infected with high-risk HPV (HPV early genes E6E7 integrated into host genome) develop cancers, indicating other co-factors' involvement contributing to this. Bacterial pathogen Chlamydia infections are epidemiologically implicated as a potential co-factor that drives cervical cancer development in collaboration with HPV. Despite their strong association, and studies describing the interaction of persistent HPV or Chlamydia with host cells, thus far, it is unknown how coinfection impacts the host tissue. To date, most of the host-pathogen studies are performed using cancer cell lines that mostly fail to reflect the physiological interactions.  We apply our novel cervical organoid models and complementary technologies like single-cell sequencing and spatial microscopy to investigate the Chlamydia, HPV, and coinfection dynamics and their impact on the host epithelial tissue.

Esophageal adenocarcinoma (EAC) incidence has increased by 500% during the past four decades, predominantly in males from industrial countries. Barrett's esophagus (BE) is a pre-malignant lesion of EAC that develops at the gastro-esophageal junction (GEJ). Several risk factors are associated with BE development, including gastro-esophageal acid reflux disease, altered microbiota, altered diet, yet BE development mechanisms are unclear. The single-layered columnar epithelium of the stomach and stratified squamous epithelium of the esophagus meet to form the GEJ. During BE development, the esophagus's stratified epithelium at the GEJ is replaced with epithelium that constitutes the stomach and intestinal epithelium characteristics. Despite the BE's pathological importance, it is unclear which changes in the GEJ contribute to the development of BE. Understanding what is normal is critical to identify factors that are altered during disease development. In the lab, we are investigating the GEJ homeostasis and the interplay of microbes with evolving tissue microenvironment during BE and cancer devlopement.