Abstract

More than 200 million people are afflicted with schistosomiasis; infection with Schistosoma japonicum and S. mansoni causes hepatointestinal schistosomiasis and S. haematobium causes urogenital schistosomiasis (UGS). UGS is associated with hematuria, major bladder wall pathology and hydronephrosis leading to kidney damage, whereas chronic deposition of eggs of S. haematobium frequently leads to squamous cell carcinoma of the bladder. Functional genomic studies will facilitate the characterization of the role and essentiality of newly available genome sequences of the three major human schistosomes. To develop transgenesis for these pathogens, we have previously demonstrated that VSVG -pseudotyped murine leukemia virus (MLV) can transduce eggs of schistosomes leading to chromosomal integration and germline transmission of reporter transgenes and short hairpin RNA cassettes, facilitating the development of stable transgenic lines. However, a sustained and robust transgene expression has been a challenge. Different strategies, including insulators, modification of epigenetic marks, exogenous cis-regulatory elements including conditional promoters, schistosome tissue-specific promoters, codon optimization to improve transgene translation, and antibiotic selection of retroviral-transduced parasites are being evaluated. Recently, we investigated whether lentiviruses, including VSVG -pseudotyped human immunodeficiency virus type 1 (HIV-1) might be utilized for transgenesis of schistosomes. It is expected that these functional approaches will facilitate the study of schistosomes, host-parasite interactions and fluke-associated diseases. In this regard, our group is also interested on developing model systems and functional tools to investigate the role of Schistosoma haematobium in squamous cell carcinoma of the bladder and the liver fluke Opisthorchis viverrini in bile duct cancer.