The Igarashi laboratory focuses on transcription gene regulation, kidney development, and kidney diseases including polycystic kidney disease (PKD), and autosomal dominant tubulointerstitial kidney disease (ADTKD). The laboratory has produced unique lines of transgenic mice that have been widely utilized for studies involving kidney-specific transgene expression and gene targeting.
Current Research Projects
Hepatocyte Factor-1B regulation of axon guidance signaling in the developing kidney
HNF-1β is essential for kidney development. Using ChIP-seq, we identified novel HNF-1β binding targets during kidney development. We found that HNF-1β binds to and regulates the expression of axon guidance genes in kidney epithelial cells. We are investigating the role these genes play in directing kidney development, and how their dysregulation may lead to defects in kidney development.
The regulation of the canonical Wnt signaling by HNF-1beta
To investigate the molecular mechanisms on how HNF-1beta regulates Wnt pathway gene transcription and the significance of dysregulated Wnt signaling in renal cystogenesis and fibrogenesis using mouse models.
Role of LncRNA in pathogenesis of PKD
LncRNAs have been recently implicated in a range of diseases including cancer; however little is known about their role in kidney development or kidney disease. Dr. Aboudehen is focused on conducting work aimed at discovering therapeutic LncRNAs that prevents or mitigates cyst formation and/or progression in PKD. Utilizing multiple mouse models of PKD, a comprehensive list of known and novel LncRNAs that are dysregulated in PKD have been established and are currently being investigated.
Utilizing ex-vivo kidney culture to investigate PKD
The paucity of in vitro models to investigate ADPKD has hindered research towards identifying therapeutic targets and novel treatments. Recent novel findings show the feasibility of utilizing the metanephric organ culture (MOC) to rapidly and inexpensively screen and identify novel genes and pathways that are involved in cystogenesis. Utilizing adeno-associated viruses to manipulate gene expression in the organ culture demonstrated the feasibility of utilizing this approach.
- Karam Aboudehen, PhD, Assistant Professor of Medicine
- Svetlana Avdulov, PhD, Lab Manager
- Siu Chiu Chan, PhD, Assistant Professor of Medicine
- Kara Eckberg, Researcher 2
- Clarke Sauve, Researcher 2
- Annie Shao, Graduate School Fellow