Professor Richard J Ross MD FRCP

Prof Richard Ross

Academic Unit of Diabetes, Endocrinology and Reproduction
University of Sheffield
E Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX
UK

Office: EU14

Tel: +44 (0)114 215 9089
Secretary Mrs Lindsey Crowson: +44 (0)114 215 9004
Fax: +44 (0)114 271 1863

Email: r.j.ross@sheffield.ac.uk or l.crowson@sheffield.ac.uk

Biography

I trained in medicine at The Royal London Hospital (1974-1979) and in Endocrinology at St Bartholomew´s Hospital, London (1983-1988). I was appointed to Sheffield University in 1995 and am Head of the Unit of Diabetes and Endocrinology. I previously served on the Medical School Council as Head of Section for Endocrinology and Reproduction (2005-2008).

My research and clinical interests are in pituitary disease, transition endocrinology and the late effects of cancer therapy. My research has yielded some 130 papers in peer reviewed journals, over 50 chapters and two books. I have a particular interest in commercial research, and I am a Director of Sheffield Health Innovation Centre and a founding Director of two university spin-out companies; Asterion Ltd and Diurnal Ltd. I am an inventor on over 250 patents, 24 granted and I personally obtained Orphan Drug Designation from the EMEA for Chronocort; a new therapy for Adrenal Insufficiency.

Research Interests

The focus of both my clinical and basic research is on optimising pituitary hormone replacement. My group have identified and characterised uncommon mutations in the growth hormone receptor which have led to fundamental observations on the mechanism by which the growth hormone receptor signals through a pre-formed dimer. This work has led to a greater understanding of the regulation of growth hormone secretion and recently the group have developed a long acting form of growth hormone which has exceptional pharmacokinetic properties that means administration may only be required once a fortnight or once a month. This work was published in Nature Medicine in 2007.

The Clinical Research Programme has been investigating different regimens for replacing cortisol, testosterone and oestrogen in hypopituitary, hypogonadal and adrenal insufficient patients. The group have designed a new modified release form of hydrocortisone, Chronocort, which in phase 1 studies has proven to replicate the normal circadian rhythm of cortisol. This work is currently being taken through to phase 2 studies in congenital adrenal hyperplasia patients. Other work has examined the incidence of hypogonadism in cancer survivors and optimising oestrogen replacement in young women of fertile years.

I co-chair the Endocrine Unit Management Team which consists of 6 Consultant Endocrinologists and runs a number of unique and innovative specialist clinics in the Health Care Trust including: Pituitary Clinic, Transition Clinic for Paediatric Endocrinology, Late Effects Clinic for Cancer survivors, Joint Surgical Endocrine Clinics, Obesity Clinic, Genetic Endocrine Clinic and a Pituitary Multidisciplinary Team.

Publications and Patents: 234 publications during career, 34 publications in the last 5 years, Scopus h-index of 34, 7 papers cited over 100 times, 2 over 200 times and 1 over 300 times.  35 patents granted from 7 independent patent families.

  1. Patent granted 2010: C Strasburger, M Bidlingmaier, Z Wu, G Matarese, R Ross. Leptin antagonist and method for quantitative measurement of leptin. US 7,807,154 B2
  2. Patent granted 2012: R Ross, P Artymiuk, J Sayers.  Fusion protein compromising growth hormone and growth hormone receptor. US 8,173,782 B2

Teaching Interests

I lecture medical students in Endocrinology. In the last 5 years I have supervised 6 PhD students, 4 awarded and 2 submitting 2010/2011. I currently supervise 2 medical students doing an intercalated research degree (BMedSci), and both BMedSci students I supervised last year achieved 1st class degrees. I gave over 5 invited lectures at international meetings per year in the last 5 years (2010: Manchester, Salt Lake City, San Diego, Liege, Turin, La Jolla) including an invitation to a Gordon conference in 2008 and a Keystone meeting in 2010.

Professional Activities

Editorship
Editorial Board Clinical Endocrinology 1996-2000
Editor: Growth and Growth Factors 1986-2006
Editorial Board: Journal of Endocrinological Investigation 2004-07
Editorial Board: Journal of Clinical Endocrinology & Metabolism 2010-
Advisory Boards
NICE appraisal of adult growth hormone replacement 2003-04
Member of Lilly HYPOCCS International Advisory Board 1999-2007

* Society for Endocrinology
- Joined the Society for Endocrinology Media Committee 2009
- SFE Nomination Committee 2010
- A Director of Bioscientifica (2007), the company that supports the Society for Endocrinology and promotes endocrinology internationally.
- I chair the Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE) which is a national group undertaking major research in the management of patients with congenital adrenal hyperplasia. We completed a study of over 200 patients published in J Clin Endocrinol Metab 2010.

* University Spin Out Companies
- Founding Director Asterion Ltd, MD 2001-06, CSO 2006-
- Founding Director Diurnal Ltd, MD 2005-
* Patents
- 253 Applications, 24 Granted
* National Committee Membership
- Council Member, Society for Endocrinology 1999-01
- Society for Endocrinology Clinical Subcommittee, Audit 1997-99, Program Organiser 2000-02
* Commercial
- 27.7.2005 - Awarded Orphan Drug designation by the EMEA (EU/3/05/296) for modified release hydrocortisone (Chronocort) for the treatment of Congenital Adrenal Hyperplasia

Current Projects

2003 – 2010 Weston Park Hospital Cancer Appeal. Late Effects of Cancer Survivors. £562,083. Co-Applicant.
2004 – 2010 Asterion Ltd. Development of Cytokine Agonists and Antagonists. £1M. Lead.
2007 – 2010 HEIF. Sheffield Medical Innovation Centre. £172,000. Lead.
2010 – Testosterone Replacement in Young Men after Cancer Therapy. CRUK. £500,000. Lead
2011 - 2015 EU FP7 (TAIN). Treatment of Adrenal Insufficiency in Neonates. 4,2000,000 Euros. Lead
2011 - 2015 Sheffield Healthcare Gateway.  HEIF UoS Grant. £1,165,494.  Lead
2012 - 2014 MRC Confidence in Concept Grant. £350,000. Co-Applicant.

Recent Publications

To access selected publications visit myPublications

Ross RJM, Rodda C, Tsagarakis S, Davies PSW, Grossman A, Rees LH, Preece MA, Savage MO, Besser GM. Treatment of growth hormone deficiency with growth hormone releasing hormone. Lancet 1987;1:5-8.

Reardon W, Ross RJM, Sweeney MG, Luxon LM, Pembrey ME, Harding AE, Trembath RC. Diabetes mellitus due to a pathogenic mitochondrial DNA point mutation. Lancet 1992;II:1376-1379.

Ross RJM, Esposito N, Shen XY, Von Laue S, Chew SL, Postel-Vinay M-C, Finidori J. A short isoform of the human growth hormone receptor functions as a dominant negative inhibitor of the full length receptor and generates large amounts of binding protein. Mol Endocrinol 1997;11:265-273 .

Ayling RM, Ross R, Towner P, Von Laue S, Finidori J, Moutoussamy S, Buchanan CR, Clayton PE, Norman MR. A dominant negative mutation of the growth hormone receptor causes familial short stature. Nat Genet 1997;16:13-14.

Maamra M, Finidori J, Laue S, Simon S, Justice S, Webster J, Dower SK, Ross RJM. Growth hormone and its antagonist are very rapidly internalized independent of signaling by the full length but not truncated human receptor. J Biol Chem 1999;274:14791-14798.

H Zarkesh-Esfahani, G Pockley, RA Metcalfe, M Bidlingmaier, Z Wu, A Ajami, AP Weetman, CJ Strasburger, RJM Ross. High dose leptin activates human leukocytes via receptor expression on monocytes. J Immunol 2001; 167: 4593-4599.

DB Savage, M Agostini, I Barroso, M. Gurnell, J.A. Luan, A. Meirhaeghe, A-H Harding, G. Ihrke, O Rajanayagam, MA Soos, S George, D Berger, EL Thomas, JD Bell, K Meeran, R Ross, A Vidal-Puig, NJ Wareham, S O´Rahilly, VKK Chatterjee, AJ Schafer. Digenic Inheritance of Severe Insulin Resistance in a Human Pedigree. Nat Genet 2002;31:379-384.

KC Leung, M Ballesteros, K Sjogren, CKW Watts, TH Low, GM Leong, RJM Ross, KKY Ho. Estrogen inhibits growth hormone (GH) signalling by suppressing GH-induced JAK2 phosphorylation: an effect mediated by SOCS2. PNAS 2003;100:1016-21.

Newell-Price J, Whiteman M, Rostami-Hodjegan A, Darzy K, Shalet S, Tucker GT, Ross RJM Modified-release hydrocortisone for circadian therapy: A proof of principle study in dexamethasone-suppressed normal volunteers. Clin Endocrinol Accepted Article Online: 26 Jul 2007. doi: 10.1111/j.1365-2265.2007.03011.x.

Wilkinson IR, Ferrandis E, Artymiuk PJ, Teillot M, Soulard C, Touvay C, Pradhananga SL, Justice S, Wu Z, Leung KC, Strasburger CJ, Sayers JR, Ross RJ A ligand-receptor fusion of growth hormone forms a dimer and is a potent long-acting agonist. Nat Med 2007;9:1108-1113

J Newell-Price, M Whiteman, A Rostami-Hodjegan, K Darzy, S Shalet, GT Tucker and RJM Ross Modified-release hydrocortisone for circadian therapy: A proof of principle study in dexamethasone-suppressed normal volunteers. Clinical Endocrinology 2008 Jan;68(1):130-5

Absolom K, Eiser C, Turner L, Ledger W, Ross R, Davies H, Coleman R, Hancock B, Snowden J, Greenfield D 2008 Ovarian failure following cancer treatment: current management and quality of life. Hum Reprod 23:2506-2512

Siyambalapitiya S, Jonsson P, Koltowska-Haggstrom M, Gaillard R, Ho K, Ross RJ 2008 A cross-sectional analysis of testosterone therapies in hypopituitary men on stable pituitary hormone replacement. Clin Endocrinol (Oxf) 70:907-13

Rinomhota AS, Bulugahapitiya DU, French SJ, Caddy CM, Griffiths RW, Ross RJ 2008 Women gain weight and fat mass despite lipectomy at abdominoplasty and breast reduction. Eur J Endocrinol 158:349-352

Debono M, Ross R, Newell-Price J 2009 Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy. Eur J Endocrinol 2009 160:719-29

Miguel Debono, Cyrus Ghobadi, Amin Rostami-Hodjegan, Hiep Huatan, Michael J Campbell, John Newell-Price, Ken Darzy, Deborah P Merke, Wiebke Arlt, and Richard J Ross Modified-release hydrocortisone to provide circadian cortisol profiles. J Clin Endocrinol Metab 2009,94:1548-54

Michel G, Greenfield DM, Absolom K, Ross RJ, Davies H, Eiser C 2009 Follow-up care after childhood cancer: survivors' expectations and preferences for care. Eur J Cancer 45:1616-1623

Debono M, Price JN, Ross RJ 2009 Novel strategies for hydrocortisone replacement. Best Pract Res Clin Endocrinol Metab 23:221-232

Greenfield DM, Walters SJ, Coleman RE, Hancock BW, Snowden JA, Shalet SM, DeRogatis LR, Ross RJ Quality of life, self-esteem, fatigue, and sexual function in young men after cancer: a controlled cross-sectional study. Cancer 2010:116:1592-1601

Wass J, Toogood A, Brabant G, Ball S, Ross R Survivors of childhood cancer. Integrated follow-up is needed. BMJ 2010:340:c588

Verma S, Vanryzin C, Sinaii N, Kim MS, Nieman LK, Ravindran S, Calis KA, Arlt W, Ross RJ, Merke DP A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (Chronocort) vs conventional hydrocortisone (Cortef) in the treatment of congenital adrenal hyperplasia. Clin Endocrinol (Oxf) 2010: 72:441-447

E Ferrandis, S L Pradhananga, C Touvay, C Kinoshita, I R Wilkinson, K Stafford, Z Wu, C J Strasburger, J R Sayers, P J Artymiuk and R J Ross Immunogenicity, toxicology, pharmacokinetics and pharmacodynamics of growth hormone ligand-receptor fusions. Clin Sci (Lond) 2010, 119:483-491

W Arlt, D S Willis, S H Wild, N Krone, E J Doherty, S Hahner, T S Han, P V Carroll, G S Conway, D A Rees, R H Stimson, B R Walker, J M Connell and R J Ross Health Status of Adults with Congenital Adrenal Hyperplasia: A Cohort Study of 203 Patients. J Clin Endocrinol Metab 2010 Epub Date: 2010/08/20

M Whitaker, M Debono, H Huatan, D Merke, W Arlt and R Ross An oral multi-particulate, modified release, hydrocortisone replacement therapy that provides physiological cortisol exposure.  Clinical Endoccrinology 2013 Doi: 10.1111/cen. 12316