Androgen receptor
Androgen receptor protein (green labelling) is abundant in granulosa cells (GC) of a human antral follicle. Cell nuclei are labelled by DAPI (blue). Theca layer (TC) is also shown.

Contact

For more information on this area of research

Professor Stephen Franks
+44 (0)20 7594 2109
s.franks@imperial.ac.uk

Real time confocal imaging of LH-induced endocytosis of FLAG-tagged LH receptor in HEK 293 cells. Time stamp indicates start of LH treatment.

What we do

We are strong in the areas of ovarian physiology and dysfunction, epigenetic programming, stem cell biology and receptor signalling, all of which impact on reproductive and post-reproductive health. Current research in each of these areas integrates basic science, animal models and experimental medicine, which go hand-in-hand with advances in clinical practice.

Why it is important and how current research addresses the important issues

Gonadotropin hormone receptors is a key area in understanding both gonadal physiology and dysfunction (led by Dr Aylin Hanyaloglu). Her expertise extends to the study of other G protein coupled receptors (GPCRs) that are important in reproductive and metabolic dysfunction and offer potential targets for new drugs. Complementary to these studies are those focusing on steroid/growth factor interactions and their role in reproductive function (Profs Kate Hardy and Stephen Franks).

Understanding mechanisms of regulation of stem cells and how this may translate into benefit to human health is a rapidly growing and increasingly important area (Drs Wei Cui and Veronique Azuara). Studies have uncovered fundamental mechanisms of stem cell regulation, while functional intervention studies, including those involving gene transfer, provide proof of principle for further clinical development. Stem cells, and their ex vivo manipulation, have great potential for improved treatment of a wide variety of diseases. Epigenetic regulation of stem and progenitor cells (Veronique Azuara and Wei Cui) has a key role in maintaining tissue homeostasis and translation into regenerative medicine. Epigenetic regulation by microRNAs appear to have a role in oocyte maturation and fertility with implications for normal fertilisation and embryo development (Dr Shirin Khanjani).

Epigenetic regulation plays an important part in the in-utero programming of adult disease which increasingly is being acknowledged as a key to future population health but it is not only events during early life that have an impact on disease in later life. Infertility and menstrual disturbances are common and distressing problems and their investigation and management are an important element of clinical research and practice (Shirin Khanjani, Stephen Franks) The common endocrine disorder of polycystic ovary syndrome (PCOS) has both reproductive and metabolic consequences.

A healthy environment for reproduction has a key influence on the events that lead to successful conception, a normal pregnancy, infant welfare and long-term health in the adult. Oocyte quality is the key determinant of fertility determined not only by local ovarian factors but also by the metabolic milieu that, in turn, may be adversely influenced by factors such as obesity and endocrine disorders of ovulation. Ovarian dysfunction during the reproductive years is associated with adverse health events in later adulthood. This phenomenon is illustrated by the increased risk of diabetes in women with PCOS (Stephen Franks and Kate Hardy) and cardiovascular disease risk in women who suffer premature ovarian insufficiency (POI). PCOS is a major risk factor for endometrial cancer, a key area for collaborative studies with members of the Division of Cancer within the IRDB (Dr Mara Kyrigou, Dr Hector Keun with Stephen Franks and Kate Hardy). There is evidence that disordered expression and function of GPCRs (including the LH receptor) have an impact on development of gynaecological cancers and this is another active area of collaborative research (Aylin Hanyaloglu, Prof Hani Gabra, Dr Sadaf Ghaem-Maghami).

Impact

Members of this group have recently published key papers in the leading journals in the specialties including Development, Stem Cells, Nature Communications, Journal of Biological Chemistry, Endocrinology and The Journal of Clinical Endocrinology & Metabolism. They have delivered plenary lectures at prestigious national and international meetings and disseminated their work by oral communications or posters at key meetings in cell biology, endocrinology and cancer.

Lead researchers

Our researchers