The Anne-Jorgensen Group, which is part of the Dept. of Growth and Reproduction, Rigshospitalet, aims to understand the molecular and cellular mechanisms underlying human gonadal sex differentiation, gonad and adrenal organogenesis and sex-specific fetal germ cell differentiation - in normal development and in disease.
Main research areas include:
Delineation of signalling cascades directing human fetal testis, ovary and adrenal development.
The aim of this research is to identify the signalling pathways directing development of human gonads and adrenals during early fetal life. Using ex vivo tissue culture approaches we specifically manipulate signalling pathways involved in sex-specific differentiation of the gonads, cell lineage specification and the sex-specific fetal germ cell development – to examine effects on gonadal function, morphology and cell lineages. Our research in this area has recently demonstrated a role for the Nodal signalling pathway in the regulation of germ cell pluripotency factor expression and establishment of seminiferous cords in human fetal testes.
Characterisation of signalling pathways dysregulated in patients with Differences of Sex Development.
With this research we aim to determine the molecular mechanisms underlying the gonadal and adrenal phenotypes observed in patients with differences of sex development (DSD). Our approach is to combine information from our ex vivo fetal gonad and adrenal culture models, in which we can manipulate pathways involved in specific DSD conditions, with information obtained from patient samples. This research will increase the understanding of sequential cellular events and functional consequences of selected types of DSD on gonadal and adrenal development.
Identification of altered germ cell – somatic niche interactions in the initiation of testicular cancer.
The testicular cancer precursor, germ cell neoplasia in situ (GCNIS), originates from fetal germ cells which fail to differentiate during early fetal development. We wish to understand how altered signalling between the cell lineages of the developing testes leads to arrest of germ cell differentiation using ex vivo culture models of human fetal testes and adult testicular tissue containing GCNIS cells - to examine the initial step in the malignant transformation of germ cells. Our research in this area has demonstrated dysregulation of the mitosis-meiosis switch in GCNIS cells, suggesting involvement of this pathway in the initiation of testicular cancer.
Current team members
Cecilie Melau, Katrine Harpelunde Poulsen, Bonnie Håkansson, Hein Stroomberg
Durga Kolla, Valentina Mularoni, Sarah Moody
Kristina Vile Jensen, Christiane Rudolph
Dr. Rod T. Mitchell, Center for Reproductive Health, University of Edinburgh.
Dr. Humphrey Yao, Reproductive Developmental Biology Lab. NIEHS/NIH.
Prof. Andrew Sinclair, Murdoch Children’s Research Institute, Melbourne.
Prof. Ken McElreavey, Human Developmental Genetics, Institute Pasteur.
Prof. Lene Juel Rasmussen, Center for Healthy Ageing, University of Copenhagen.