Research Director Thue W. Schwartz
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Curriculum in Brief
Thue W. Schwartz is presently Professor of Molecular Pharmacology at University of Copenhagen coming from a background in both academia/MRC research professor; in the pharmaceutical industry /VP of research in Corporate Research at Novo Nordisk; and in biotech / founder and chief scientific officer of the biotech company 7TM Pharma A/S devoted to discoveries of pharmaceuticals against metabolic diseases based on his molecular pharmacology research.
Currently Dr. Schwartz is head of the cross disciplinary "Food Fitness & Pharma" UNIK directed against life style diseases (~20 M EUR grant from the Danish Ministry of Science and Innovation, 2009-13).
Awards and Honors
Thue W. Schwartz has received a number of prizes and honors including the Anders Jahre Prize (Olso), the Novo Nordisk Foundation Prize and the Lundbeck Foundation Price and has served on the editorial board of a number of journals such as Mol. Pharmacol. and J. Med. Chem.
He has also served on the Scientific Advisory Board of a number of biotech companies and biotech investment funds in Denmark, USA and Canada and on the Board of Directors of companies such as Neurosearch A/S.
He was in 1994 elected as member of the Royal Danish Academy of Science and Letters.
Dr. Schwartz has worked on molecular endocrinology and molecular pharmacology with enteroendocrine peptide hormones, neuropeptides and their receptors as the main theme. Initial physiological contributions in the field included the demonstration that pancreatic polypeptide is a hormone and characterization of its control through vago-vagal mechanisms and the use of this as a measure of vagal activity, damage and neurophathy.
Biochemical contributions included isolation and characterization of novel endocrine peptides and the identification of mono-basic cleavage as a major peptide precursor processing mechanism.
Initial pharmacological contributions included identification of novel Y receptor subtypes and the design of prototype receptor subtype selective ligands. Subsequently Dr. Schwartz pioneered modern molecular pharmacology by demonstrating through receptor mutagenesis combined with medicinal and computational chemistry that non-peptide drug candidates work through a surprising novel, allosteric mechanism. This work has served as the basis for the development of knowledge-based drug discovery methods used for example in his company, 7TM Pharma A/S.
Based on molecular pharmacological work in a number of different receptors and using meticulous, metal-ion site engineering as tools Dr. Schwartz identified a unifying Global Toggle Switch Model for the molecular mechanism of action of 7TM receptors, the largest family of proteins in the human genome and major target of medical drugs.
In recent years, Dr. Schwartz has returned to the basic research work in the field of enteroendocrinology, combining molecular and computational pharmacology with the development of novel transgenic animal models.
He is, for example the sole inventor of two drug candidates based on enteroendocrine hormones which both have been taken into clinical phase-II studies and has authored approx. 250 scientific publications of which 9 are published in Nature or Science (6 of which as first and/or corresponding author) and he has an h-index of 59 and an average number of citations per publication of 45 (ISI).
Key Recent Discoveries
• Common structural basis for constitutive activity in the ghrelin receptor family
Identification of the ghrelin receptor and its constitutive activity as being involved in regulation of food intake, for example B. Holst, N. Holliday, A. Bach, C. E. Elling, H. Cox & T. W. Schwartz: .
J. Biol. Chem. (2004) 279:53806-53817. (cited more than 80 times).
• Molecular Mechanism of 7TM Receptor Activation - a Global Toggle Switch Model
Identification of the molecular activation mechanism for 7TM receptors, the large family of proteins in the human genome, reviewed in T.W.Schwartz, T.M.Frimurer, B.Holst, M.M.Rosenkilde & C.E.Elling.
Annu. Rev. Pharmacol. Toxicol. (2006) 46: 481-519 (cited more 80 times).
• GPR39 deficiency is associated with pancreatic islet cell dysfunction
Identification of the GPR39 receptor as an important regulator of pancreatic islet function, for example B.Holst, K.L.Egerod, C.Jin, P.S.Petersen, M.V.Østergaard, J.Hald, J.Størling, T.Mandrup-Poulsen, J.J.Holst, P.Thams, C.Ørskov. N.Wierup, F.Sundler, O.D.Madsen & T.W.Schwartz: .
Endocrinology (2009) 150: 2577-85.