Edinburgh Research Explorer

Prof Lee Smith

Personal Chair of Genetic Endocrinology

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Willingness to take PhD students: Yes

Education/Academic qualification

Doctor in Philosophy, University of Warwick
Bachelor of Science, University of Leicester

Biography

I began my career with a PhD in Molecular Genetics at the University of Warwick, UK. I then completed two postdoctoral positions at the MRC Mammalian Genetics Unit in Harwell, UK, working on mammalian sex determination and testis development. I moved to Edinburgh in 2006 to lead a UK Medical Research Council funded programme of research within the MRC Human Reproductive Sciences Unit. In 2012, I was promoted to Chair of Genetic Endocrinology and now work as a Principal Investigator at the newly inaugurated MRC Centre for Reproductive Health within the University of Edinburgh. Although I retains interests in many aspects of reproductive genetics and endocrinology, my group’s primary focus is on elucidating the role of testosterone signaling in male development and lifelong health.

 

Background

The adult testis is essentially a factory, which produces two key products, – the synthesis and secretion of steroid hormones, notably testosterone (made by testicular Leydig cells), and the production of mature sperm from spermatogonial stem cells (a process known as spermatogenesis). My group is working both to understand how these processes are regulated and to develop new mechanisms to support both male fertility and life-long health and wellbeing.

 

Major research interests

Androgen action is a strategically important research field as it is implicated in a wide range of disease states such as diabetes, cardiovascular disease, ageing and obesity, in addition to its role in reproductive health and fertility. This firmly places the testis, as the ‘androgen factory’, at the position of fulcrum between disease and possible therapeutics. I hold a unique and world-leading position as I have independently developed and published a wide range of models that together allow me to elegantly dissect and understand the system in unrivalled detail. In an increasingly ageing and obese society this understanding will be invaluable.

I have collaborated with Professor Richard Sharpe to identify a universal male programming window (MPW) essential for male development (published in J Clin Invest). Ano-genital distance, a life-long marker of androgen action in the MPW, which we identified in our studies, has recently been validated in clinical trials as a metric for infertility and Testicular Cancer risk. More recently we have identified the progenitor population of the adult Leydig cells and demonstrated that androgenic fetal programming of this cell-type impacts adult testosterone production (published in PNAS), and also demonstrated that Sertoli cells provide a key role in promotion of adult Leydig cell development (published in Development).

I have demonstrated that Sertoli cells enforce peritubular myoid cell fate in the postnatal testis (published in Development) and independently demonstrated that targeted ablation of androgen receptor (AR) in testicular Peritubular Myoid cells results disrupted testis function and infertility, despite over 100 years of study, the first ever in vivo function unequivocally ascribed to this cell-type (published in FASEB J and Int Journ Androl). I have also demonstrated for the first time that AR is an essential requirement for correct function in adipose tissue (published in Diabetes), peripheral vasculature (published in Cardiovascular Research), Seminal Vesicles (published in Endocrinology), Leydig cells (published in FASEBJ) testicular vasculature (Published in PLoS ONE), the epididymis (published in Endocrinology) and the Prostate (published in Endocrinology). I have also simultaneously directed two British Heart Foundation-funded research projects (as PI) in cardiovascular sciences, one of which has been published (Cardiovascular Research), and the mouse model exploited commercially. In addition, my recent publications on potential targets for non-hormonal male contraceptives in PLoS Genetics led to world-wide media interest, and the paper itself became the most highly accessed article of May and June in PLoS Genetics, - and in the first three months receiving greater than 10,000 views.

Future research is focussed upon ‘testis control of androgen production’. Exploiting the stem cell niche within the testis to manipulate androgens as a therapeutic tool for human health benefit. This will utilise many of the existing transgenic models I have generated, alongside new models of premature ageing arising from my co-ordinator role with EuCOMM; a novel ‘Gene Therapy’ approach, and advances in stem cell approaches I am developing in collaboration with the MRC Centre for Regenerative Medicine. These future research plans are fully funded through external grant awards.

 

Recent progress – see http://www.crh.ed.ac.uk/professor-lee-smith%E2%80%A8/

 

Group Members

Laura O’Hara, Postdoctoral Fellow

Cornelia Roesl, Postdoctoral Fellow

Diane Reboucet, Postdoctoral Fellow

Junxi Wu, Postdoctoral Fellow

Laura Milne, Lab Manager

Sarah Smith, Research Technician

Lyndsey Cruikshanks, Technician

Nathen Jeffery, Technician

Michael Curley, PhD

Saloni Patel, PhD

Anne-Louise Gannon, PhD

Tina Tsai, PhD

Annalucia Darbey PhD

 

Collaborations

Prof Peter O’Shaughnessy; University of Glasgow

Prof Serge Nef; University of Geneva

Dr Rod Mitchell; University of Edinburgh

Prof Nik Morton; University of Edinburgh

Prof Colin Selman; University of Glasgow

Dr Will Walker; University of Pittsburgh

Dr Mark Strachan; University of Edinburgh

 

Elected Fellowship

Fellow of the Society of Biology (FSB)

 

Society membership

Member of the American Society of Andrology

Member of the Society for Reproduction and Fertility

Member of the Genetics Society

 

Membership on Panels/Boards

2012 - onwards: Appointed to BBSRC Pool of Experts

2012- onwards: Chair University of Edinburgh ‘MSc Reproductive Health’ Exam Board

2012- onwards: Editorial Board member ‘Andrology’ Journal

2012- onwards: Editorial Board member ‘Molecular and Cellular Endocrinology’ Journal

2011- onwards: Editorial Board member ‘The Scientific World’ Journal

 

Awards/Special Invitations

2015: Benchmark Plenary Lecture: Androgens in lifelong health and wellbeing. American Testis Workshop, Salt lake City, Utah, USA

2012: Plenary Lecture: ‘The future of Andrology Research’. 7th European Congress of Andrology, Berlin, Germany

2011: Plenary Lecture: ‘mouse genomics, the power of EuCOMM’ European Teratology Society meeting, Gent, Belgium

2010: Plenary Lecture: ‘Exploiting mouse genetics in reproductive biology’ Young Researchers in Male Fertility meeting, Elba, Italy

 

Research activities & awards

  1. Found Animals Foundation

    Activity: Participating in or organising an event typesParticipation in conference

  2. American Testis Workshop

    Activity: Participating in or organising an event typesParticipation in workshop, seminar, course

  3. University of Newcastle, Australia

    Activity: Participating in or organising an event typesParticipation in conference

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