Nuclear Receptors are, physiologically and pharmacologically, a critical superfamily of transcription factors. They drive key processes at every stage from development and reproduction to ageing and cancer. They are critical determinants of everyday health via their roles in metabolism and circadian rhythms. Nuclear receptors allow external factors to influence cellular pathways and the fact that many bind and are activated by small molecules means they represent highly druggable targets; currently, 13% of FDA-approved drugs target nuclear receptors.
This meeting will address the new roles and novel crosstalk mechanisms that are emerging for many of the 48 human nuclear receptors, in health and disease. For example, it has long been known that the estrogen receptor drives progression of breast cancer, and patients with estrogen receptor-positive disease are treated using antiestrogens or aromatase inhibitors to inhibit estrogen signalling. Now however, it is apparent that the androgen receptor can in some cases drive breast cancer progression and is a therapeutic target, resulting in clinical trials for androgen receptor-targeting therapies in advanced breast cancer. The androgen receptor, itself long the main therapeutic target in prostate cancer, is emerging as a key player in metabolic disease, while conversely other nuclear receptor including the glucocorticoid receptor and several orphan nuclear receptors are implicated in prostate cancer progression. Meanwhile, given the impact of many nuclear receptors on the central nervous system, it is unsurprising that they are being explored in the context of neurological disorders and depression. Thus there is wide scope for re-purposing of licensed drugs and development of new NR-targeting therapies for a host of conditions and diseases.
Crosstalk between nuclear receptors and other fundamental processes is another exciting expanding area that will also be covered. DNA damage repair pathways are inextricably linked to steroid signalling via transcriptional processes, with implications for drug combinations in several diseases. Hitherto unsuspected roles of nuclear receptors in epigenetic control and the processing and function of non-coding RNAs opens up to capacity of this superfamily to further means of impacting on development and normal functioning, but also on disease development.
This unique meeting will bring together many of the leading figures in nuclear receptor research from across the globe, to discuss emerging roles and their implications for health and disease – and both human and drug development – in an intimate meeting that will generate meaningful idea exchange and interaction that will help to further shape this influential field.
- Further emerging roles for nuclear receptors in cancer
- Structural insights into nuclear receptor function and crosstalk
- Nuclear receptors’ role in epigenetic regulation and non coding RNA
- Nuclear receptors and DNA damage
- Nuclear receptors and cell cycle
- Nuclear receptors in metabolism/metabolic disease
- Nuclear receptors in the CNS
Take advantage of this fantastic opportunity for students! Register an academic at the earlybird rate of $1,835 and bring a student for only $850. Unfortunately, Postdocs are not eligible. Both registration packages include; accommodation for the 24, 25, 26 February 2020 (on a shared basis for students) and a 24hour all-inclusive food and beverage package for the conference period. Academic registrations must be completed by 20 December 2019. Once registered, please contact Amy Johnson to obtain a special registration link for your student.
Confirmed Invited Speakers:
Mohamed Bentires (University Hospital, Basel)
Jason Carroll (University of Cambridge)
John Cidlowski (National Insitute of Enviromental Health Sciences)
Edwin Cheung (University of Macau)
Geoffrey Greene (University of Chicago)
Gary Hammer (University of Michigan)
Benita Katzenellenbogen (University of Illinois and College of Medicine)
David Mangelsdorf (University of Texas)
Ciara Metcalfe (Genentech)
David Moore (Baylor College of Medicine)
Donald Patrick McDonnell (Duke University)
Carol Sartorius (University of Colorado)
Scientists and Clinician Scientists at a range of levels from postdoctoral and up: Principal Investigators, Junior Team Leaders, Research Fellows. Ambitious postgraduate students in the field will also be encouraged to attend.
Relevant specialties are wide-ranging, reflecting the importance of nuclear receptors in many aspects of health and disease. These include Endocrinology, Oncology, Paediatrics, Urology, Gynaecology, Obstetric Medicine, Neuroscience, Cardiology.
Since the first cloning of the nuclear receptors in the 1980s, they have been the subject of detailed molecular investigation due to their critical roles in every aspect of cellular and physiological functioning. This has led to enormous progress in our understanding of how external factors can act via nuclear receptors to drive processes such as development, metabolism, reproduction, sexual function, and influence diseases such as metabolic syndrome, depression and cancer. Currently, around 13% of FDA-approved drugs target nuclear receptors, reflecting their unique druggability among transcription factors and pharmacological importance. Although we have known for some time that growth factor signalling can influence nuclear receptor signalling and vice versa, over the last few years, some hitherto unsuspected roles for nuclear receptors have emerged. Notable among these is the crosstalk between steroid receptors and DNA damage repair pathways, and more recently the mutual regulation between nuclear receptor signalling and microRNA action, which has far-reaching implications. Further, it is increasingly apparent that nuclear receptors have influence and action outside of the roles we have traditionally ascribed to them, and can drive processes and diseases either in normal function or in as a consequence of advanced disease (e.g. androgen receptor driving some forms of breast cancer, or glucocorticoid receptor “hijacking” androgen receptor-driven transcription in some advanced prostate tumours). There is an urgent need for integration of this knowledge across the many disciplines which nuclear receptors impact – although endocrinology meetings can combine many of these they do not encompass al. Further, as nuclear receptor research is frequently marginalised at these meetings, they are not traditionally well attended by, for examples, those in the hormone-dependent cancer field or neuroscientists. This meeting will bring together the scientists and clinicians who have made these surprising discoveries, those who are further delineating the novel mechanisms and those who are applying the new knowledge in clinical development, to discuss the ramifications and implication, the common ground and the idiosyncrasies. There is an urgent need to use this knowledge to drive both drug repurposing for existing nuclear receptor-targeted therapies, and new drug development. The intimate venue and small size will provide a unique platform for new collaborations to be formed and existing ones cemented, and meaningful knowledge and idea exchange, to really drive the next decade of research in this important area.
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