Rajesh V Thakker


Affiliation: University of Oxford
Country: UK


  1. Gorvin C, Babinsky V, Malinauskas T, Nissen P, Schou A, Hanyaloglu A, et al. A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate β-arrestin-biased signaling. Sci Signal. 2018;11: pubmed publisher
    ..Thus, our results demonstrate CaSR signaling through β-arrestin and the importance of the Arg680-Glu767 salt bridge in mediating signaling bias. ..
  2. Hannan F, Kállay E, Chang W, Brandi M, Thakker R. The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases. Nat Rev Endocrinol. 2018;: pubmed publisher
  3. Xi L, de Falco P, Barbieri E, Karunaratne A, Bentley L, Esapa C, et al. Bone matrix development in steroid-induced osteoporosis is associated with a consistently reduced fibrillar stiffness linked to altered bone mineral quality. Acta Biomater. 2018;76:295-307 pubmed publisher
    ..These results will help in the design of new composite musculoskeletal implants for bone repair. ..
  4. Stevenson M, Lines K, Thakker R. Molecular Genetic Studies of Pancreatic Neuroendocrine Tumors: New Therapeutic Approaches. Endocrinol Metab Clin North Am. 2018;47:525-548 pubmed publisher
    ..Therapies targeting epigenetic regulation and MEN1 gene replacement have been reported to be effective in preclinical models. ..
  5. Thakker R. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Mol Cell Endocrinol. 2014;386:2-15 pubmed publisher
    ..MEN4 is caused by heterozygous mutations of CDNK1B which encodes the 196 amino-acid CDK1 p27Kip1, which is activated by H3K4 methylation. ..
  6. Yates C, Newey P, Thakker R. Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1. Lancet Diabetes Endocrinol. 2015;3:895-905 pubmed publisher
    ..These challenges and controversies will be reviewed and possible approaches proposed. ..
  7. request reprint
    Thakker R. Genetics of endocrine and metabolic disorders: parathyroid. Rev Endocr Metab Disord. 2004;5:37-51 pubmed
  8. Lines K, Stevenson M, Thakker R. Animal models of pituitary neoplasia. Mol Cell Endocrinol. 2016;421:68-81 pubmed publisher
  9. Karunaratne A, Xi L, Bentley L, Sykes D, Boyde A, Esapa C, et al. Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis. Bone. 2016;84:15-24 pubmed publisher
    ..These findings provide a clear quantitative demonstration of how bone quality changes increase macroscopic fragility in secondary osteoporosis. ..

More Information


  1. request reprint
    Thakker R. Diseases associated with the extracellular calcium-sensing receptor. Cell Calcium. 2004;35:275-82 pubmed
    ..e. autoimmune) of hypoparathyroidism. Thus, abnormalities of the CaSR are associated with three hypercalcaemic and three hypocalcaemic disorders. ..
  2. Hannan F, Babinsky V, Thakker R. Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis. J Mol Endocrinol. 2016;57:R127-42 pubmed publisher
    ..In addition, calcimimetic and calcilytic drugs, which are positive and negative CaSR allosteric modulators, respectively, have been shown to be of potential benefit for these FHH and ADH disorders. ..
  3. Lines K, Vas Nunes R, Frost M, Yates C, Stevenson M, Thakker R. A MEN1 pancreatic neuroendocrine tumour mouse model under temporal control. Endocr Connect. 2017;6:232-242 pubmed publisher
    ..Thus, we have established a mouse model (Men1L/L /RIP2-CreER) to study early events in the development of pancreatic β-cell NETs. ..
  4. Gorvin C, Rogers A, Hastoy B, Tarasov A, Frost M, Sposini S, et al. AP2σ Mutations Impair Calcium-Sensing Receptor Trafficking and Signaling, and Show an Endosomal Pathway to Spatially Direct G-Protein Selectivity. Cell Rep. 2018;22:1054-1066 pubmed publisher
    ..Thus, compartmental bias for CaSR-mediated Gαq/11 endomembrane signaling provides a mechanistic basis for multidimensional GPCR signaling. ..
  5. Thakker R, Newey P, Walls G, Bilezikian J, Dralle H, Ebeling P, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97:2990-3011 pubmed publisher
    ..Thus, it is recommended that MEN1 patients and their families should be cared for by multidisciplinary teams comprising relevant specialists with experience in the diagnosis and treatment of patients with endocrine tumors. ..
  6. Piret S, Gorvin C, Trinh A, Taylor J, Lise S, Taylor J, et al. Autosomal dominant osteopetrosis associated with renal tubular acidosis is due to a CLCN7 mutation. Am J Med Genet A. 2016;170:2988-2992 pubmed publisher
    ..Thus, we identified a CLCN7 mutation in a family with autosomal dominant osteopetrosis, RTA, renal stones, epilepsy, and blindness. © 2016 Wiley Periodicals, Inc. ..
  7. Piret S, Olinger E, Reed A, Nesbit M, Hough T, Bentley L, et al. A mouse model for inherited renal fibrosis associated with endoplasmic reticulum stress. Dis Model Mech. 2017;10:773-786 pubmed publisher
  8. Babinsky V, Hannan F, Gorvin C, Howles S, Nesbit M, Rust N, et al. Allosteric Modulation of the Calcium-sensing Receptor Rectifies Signaling Abnormalities Associated with G-protein ?-11 Mutations Causing Hypercalcemic and Hypocalcemic Disorders. J Biol Chem. 2016;291:10876-85 pubmed publisher
  9. Hannan F, Howles S, Rogers A, Cranston T, Gorvin C, Babinsky V, et al. Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects. Hum Mol Genet. 2015;24:5079-92 pubmed publisher
    ..Thus, our studies demonstrate AP2σ2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue. ..
  10. Thakker R. Multiple endocrine neoplasia type 1 (MEN1). Best Pract Res Clin Endocrinol Metab. 2010;24:355-70 pubmed publisher
    ..The majority of MEN1 mutations are likely to disrupt the interactions of Menin with other proteins and thereby alter critical events in cell cycle regulation and proliferation...