Proper development of the embryo requires orchestrated regulation of gene expression
in a temporal and spatial manner. Disruption of gene regulation during embryonic development
leads to developmental disorders. My research program aims at elucidating genetic and
epigenetic mechanisms with an emphasis on gene regulation in ectodermal and neuronal
developmental disorders, specifically p63-related disorders and Kleefstra Syndrome
respectively. Several patient-derived stem cell models are established in our group:
induced pluripotent stem cells (iPSCs) that can be differentiated into disease-relevant
lineages, e.g. epithelial and neuronal lineages, and adult epidermal stem cells (epidermal keratinocytes) that can be used to study epidermal stratification. Using these patient-
derived model systems and state-of-the-art epigenomics approaches such as RNA-seq,
ChIP-seq of transcription factors and histone marks and 4C-seq, we identify gene
regulatory networks including genes and regulatory elements that control normal
developmental processes and the de-regulated circuitries that are relevant to diseases.
We also study genetics of ectodermal and neuronal developmental disorders by detecting
and interpreting genetic alterations in genes and regulatory elements that are identified
in our epigenomics studies and associated with specific disease phenotypes.
Current projects include:
- Multi-omics analyses for epithelial cell identity and related diseases
- Molecular mechanism of pathogenesis in p63-related developmental disorders
- Three-dimensional genome architecture and regulatory gene network during epidermal keratinocyte differentiation
- Identification of novel genetic mechanisms involved in orofacial clefts
Jo Huiqing Zhou obtained her PhD in Hong Kong University of Science and Technology on transcriptional regulation of a proto-oncogene EWS. In 2002 she joined Department of Molecular Biology at Radboud University Nijmegen as a postdoctoral fellow, working on transcriptional regulation by basal transcription factors. In 2007 she joined Department of Human Genetics at Radboud University Nijmegen Medical Centre as a senior postdoctoral fellow and later as an independent group leader, working on gene regulatory networks of p63-related disorders and establishing several patient-derived disease models. In 2012 she established her research group at the Department of Molecular Developmental Biology at Radboud University Nijmegen, with the research theme on understanding gene regulation in (neuro)ectodermal-related disorders. As a group leader also affiliated with Department of Human Genetics, she uses patient-derived stem cell models such as iPSCs and human primary keratinocyts as the major model systems to study disease mechanisms.
- A matter of identity: master regulator p63-orchestrated transcription factor circuitry in the epithelial cell fate determination of normal development and disease. NWO-ALW Open Competition 2018. € 273,000 for 4 years.
- Epigenetic signature of limbal stem cell deficiency and therapeutic rescue in degenerative corneal diseases. NUFFIC, van Gogh Travel Grant. 2017
- Epigenetic landscape of epidermal commitment and related diseases. KNAW-NWO Netherlands-China Exchange Joint Research Program 2016. € 40,000 for 2 years.
- Regulatory gene network in epidermal development. MEERVOUD, NWO-ALW. 2013. € 221,101 for 4 years.