Dr Soo-Hyun KimPhD
Senior Lecturer and Group Leader
Molecular and Clinical Sciences Research Institute
St. George’s Medical School, University of London
Ciliopathy, Fertility, Puberty, Neuroendocrine, Development
Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders characterised by delayed puberty and infertility due to low sex steroids production and secretion. CHH/KS patients can also exhibit rather complex developmental defects, including the brain, ear, eye, spinal cord, heart, kidney, and skeleton (cleft palate and digital malformations), along with intellectual disability, neuro-sensory (loss of sense of smell, deafness) and neuro-motor anomalies. Such a broad range of associated phenotypes found in CHH/KS potentially indicate that these are caused by overlapping signal pathways, but with different tissue specificity. However, the genetic understanding of the disease is difficult, mainly due to its reduced penetrance of the genetic mutations and usually small pedigrees.
Our investigation of the molecular and cellular mechanisms underlying CHH/KS has been conducted using various human and mouse cell lines, as well as genetically modified animal models and patient genome/exome sequencing data. This led to the identification of several new factors important in human reproductive competence and wellbeing later in life. This research will eventually reveal the novel functions of these key factors.
Since many key signalling receptors that control cell function and embryonic development are localised to the primary cilia, defects in these structures cause a remarkable range of human diseases, known as a ciliopathy. We are currently focusing on the Hedgehog signalling pathway which plays an important role in not only during the embryonic development but also maintaining homeostasis in adults, therefore, any disruptions of this pathway can result in disease conditions such as infertility and cancer.
We are trying to understand how ciliopathy and Hedgehog signalling pathway contribute to human reproductive disorders like CHH/KS. Further research on the molecular basis of the disease and the diverse signal pathways involved will help provide better diagnosis, treatment and management of the patients, as well as more precise genetic screening and counselling for the families.