Professor Daniela Riccardi

Emeritus Professor

: riccardi@cardiff.ac.uk

: Available for postgraduate supervision

The ability of cells to monitor changes in the environment is crucial to life. In humans, excessive exposure to certain noxious external cues can result in a variety of life-threatening diseases such as asthma, smoker’s cough (COPD) and scarring of the lung (pulmonary fibrosis). Previously in my laboratory we have discovered the existence of “sensors” throughout our body. Currently we are investigating: i) The ability of noxious stimuli such as smoke and urban particulate matter to activate these sensors; ii) The consequences of aberrant activation of these sensors at the molecular, cellular and whole organism level; iii) The possibility to use new and existing drugs targeting these sensors to specifically prevent currently incurable inflammatory lung disease.

Useful links

Development of inhaled CaSR antagonists, calcilytics, for asthma:

https://www.youtube.com/watch?v=jIqz46r9thU&feature=youtu.be

Calcilytics as novel therapeutics for pulmonary fibrosis:

https://www.medrxiv.org/content/10.1101/2020.03.12.20034751v1

I obtained my BA in Zoology and MRes in Physiopathological methods from the University of Milan, Italy, where I investigated mechanisms of fluid transport across mammalian epithelia. I did my PhD in Physiology working between the University of Milan and the Harvard Medical School, Boston, MA, USA, under the supervision of Prof. SC Hebert, in the Renal Division of the Brigham and Women's Hospital. There, in 1993 we identified the first G protein-coupled receptor for an ion, calcium. The paper describing the cloning of the Calcium-Sensing Receptor, CaSR, from parathyroid glands is now a "citation classic" with >2,000 citations. While in Prof Hebert lab, I was awarded a Research Fellowship from the National Kidney Foundation to identify the renal CaSR. The parathyroid and kidney CaR are the target for a novel class of small molecule drugs, the calcimimetics, which were developed for the treatment of chronic kidney disease. In 2004, calcimimetics were the first G protein-coupled receptor allosteric modulators to enter the market and in 2014 calcimimetics were within the top 100 most sold drugs. In 1997, I moved to the UK where I established my independent research group at Manchester University and in 2004 I moved to Cardiff University as a Reader, then Professor (2012) within the School of Biosciences. Currently my group is actively pursuing the development of CaSR-based therapeutics for the treatment of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis.

Honours and awards

2002 - John Haddad Young Investigator Award (AIMM/ASBMR)
2000 - The Wellcome Trust Prize for Excellence in Physiology
1995 - First Prize, Excellence in Research (ASN/NKF)

Professional memberships

2018 - European Respiratory Society
2018 - Welsh Thoracic Society
1997 - Physiological Society

Academic positions

2015 - present: Deputy Head of School
2004 - present: Reader and Professor, Cardiff University
1997 - 2004: Lecturer and Senior Lecturer, University of Manchester, UK
1993 - 1997: Research Fellow, renal Division, Harvard Medical School, Boston, MA USA

Speaking engagements

Asthma UK Day: the opportunity of asthma research in Wales (2017)

Committees and reviewing

Journal reviewer (e.g., Nature, PNAS, JCI, Science TM, Scientific Reports...)
Physiological Society Council (2012-2016)
BBSRC pool of experts (2015-2017)

2015

Lopez-Fernandez, I., Schepelmann, M., Brennan, S. C., Yarova, P. L. and Riccardi, D. 2015. The calcium-sensing receptor: one of a kind. Experimental Physiology 100(12), pp. 1392-1399. (10.1113/EP085137)
Yarova, P. L. et al. 2015. Calcium-sensing receptor antagonists abrogate airways hyperresponsiveness and inflammation in allergic asthma. Science Translational Medicine 7(284), article number: 284ra60. (10.1126/scitranslmed.aaa0282)

2014

Vazquez, M., Evans, B. A. J., Riccardi, D., Evans, S. L., Ralphs, J. R., Dillingham, C. M. and Mason, D. J. 2014. A new method to investigate how mechanical loading of osteocytes controls osteoblasts. Frontiers in Endocrinology 5, article number: 208. (10.3389/fendo.2014.00208)
Brennan, S. C., Davies, T. S., Schepelmann, M. and Riccardi, D. 2014. Emerging roles of the extracellular calcium-sensing receptor in nutrient sensing: control of taste modulation and intestinal hormone secretion. British Journal of Nutrition 111(S1), pp. S16-S22. (10.1017/S0007114513002250)
Vazquez, M., Evans, B., Evans, S., Ralphs, J., Riccardi, D. and Mason, D. 2014. Development of a novel in vitro 3D osteoblast-osteocyte co-culture model to investigate mechanically-induced signalling. International Journal of Experimental Pathology 95(3), pp. A34-A35. (10.1111/iep.12078)
Wadey, R., Pinches, M. G., Jones, H. B., Riccardi, D. and Price, S. A. 2014. Tissue expression and correlation of a panel of urinary biomarkers following Cisplatin-induced kidney injury. Toxicologic Pathology 42(3), pp. 591-602. (10.1177/0192623313492044)
Varma, S. et al. 2014. Grainyheadlike 2 distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis. AJP: Lung Cellular and Molecular Physiology 306(5), pp. L405-L419. (10.1152/ajplung.00143.2013)

2013

Lembrechts, R. et al. 2013. Functional expression of the multimodal extracellular calcium-sensing receptor in pulmonary neuroendocrine cells. Journal of Cell Science 126(19), pp. 4490-4501. (10.1242/jcs.131656)
Ward, D. T., Mughal, M. Z., Ranieri, M., Dvorak-Ewell, M. M., Valenti, G. and Riccardi, D. 2013. Molecular and clinical analysis of a neonatal severe hyperparathyroidism case caused by a stop mutation in the calcium-sensing receptor extracellular domain representing in effect a human 'knockout'. European Journal of Endocrinology 169(1), pp. K1-K7. (10.1530/EJE-13-0094)
Brennan, S. C. et al. 2013. Calcium sensing receptor signalling in physiology and cancer. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1833(7), pp. 1732-1744. (10.1016/j.bbamcr.2012.12.011)
Riccardi, D., Brennan, S. C. and Chang, W. 2013. The extracellular calcium-sensing receptor, CaSR, in fetal development. Best Practice & Research Clinical Endocrinology & Metabolism 27(3), pp. 443-453. (10.1016/j.beem.2013.02.010)
Brennan, S. C. et al. 2013. Fetal calcium regulates branching morphogenesis in the developing human and mouse lung: involvement of voltage-gated calcium channels. PLoS ONE 8(11), pp. e80294. (10.1371/journal.pone.0080294)
Brown, E. M., Hebert, S. C., Riccardi, D. and Geibel, J. P. 2013. The calcium-sensing receptor. In: Alpern, R. J., Moe, O. W. and Caplan, M. eds. Seldin and Giebisch's The Kidney (Fifth Edition)., Vol. 5. Physiology & Pathophysiology Vol. 1-2. Dordrecht: Elsevier, pp. 2187-2224., (10.1016/B978-0-12-381462-3.00063-X)

2012

Riccardi, D. 2012. Parathyroid hormone-independent role for the calcium-sensing receptor in the control of urinary calcium excretion. Journal of the American Society of Nephrology 23(11), pp. 1766-1768. (10.1681/ASN.2012090955)
Chia, P. W., Brennan, S. C., Slawin, A. M. Z., Riccardi, D. and O'Hagan, D. 2012. Allosteric agonists of the calcium receptor (CaR): fluorine and SF5 analogues of cinacalcet. Organic & Biomolecular Chemistry 10(39), pp. 7922-7927. (10.1039/c2ob26402a)
Ward, D. T. and Riccardi, D. 2012. New concepts in calcium-sensing receptor pharmacology and signalling. British Journal of Pharmacology 165(1), pp. 35-48. (10.1111/j.1476-5381.2011.01511.x)
Riccardi, D. and Kemp, P. J. 2012. The calcium-sensing receptor beyond extracellular calcium homeostasis: Conception, development, adult physiology, and disease. Annual Review of Physiology 74, pp. 271-297. (10.1146/annurev-physiol-020911-153318)

2011

Vazquez, M., Evans, B. A. J., Ralphs, J. R., Riccardi, D. and Mason, D. J. 2011. Bone in vitro 3D osteoblast-osteocyte co-culture model. International Journal of Experimental Pathology 92(6), pp. A18-A18. (10.1111/j.1365-2613.2011.00780.x)
Telezhkin, V., Brazier, S. P., Mears, R., Müller, C. T., Riccardi, D. and Kemp, P. J. 2011. Cysteine residue 911 in C-terminal tail of human BKCaα channel subunit is crucial for its activation by carbon monoxide. Pflugers Archiv-European Journal of Physiology 461(6), pp. 665-675. (10.1007/s00424-011-0924-7)
Finney, B., Wilkinson, W. J., Searchfield, L., Cole, M., Bailey, S. L., Kemp, P. J. and Riccardi, D. 2011. An exon 5-less splice variant of the extracellular calcium-sensing receptor rescues absence of the full-length receptor in the developing mouse lung. Experimental Lung Research 37(5), pp. 269-278. (10.3109/01902148.2010.545471)
Cayzac, S. H., Rocher, A., Obeso, A., Gonzalez, C., Riccardi, D. and Kemp, P. J. 2011. Spermine attenuates carotid body glomus cell oxygen sensing by inhibiting L-type Ca2+ channels. Respiratory Physiology & Neurobiology 175(1), pp. 80-89. (10.1016/j.resp.2010.09.009)
Wilkinson, W. J. et al. 2011. Alveolar epithelial CNGA1 channels mediate cGMP-stimulated, amiloride-insensitive, lung liquid absorption. Pflügers Archiv European Journal of Physiology 462(2), pp. 267-279. (10.1007/s00424-011-0971-0)
Searchfield, L., Price, S., Betton, G., Jasani, B., Riccardi, D. and Griffiths, D. F. R. 2011. Glutathione S-transferases as molecular markers of tumour progression and prognosis in renal cell carcinoma. Histopathology 58(2), pp. 180-190. (10.1111/j.1365-2559.2010.03733.x)

2010

Sourial, S., Searchfield, L., Schuppe-Koistinen, I., Betton, G. R., Riccardi, D. and Price, S. A. 2010. Application of Dolichos biflorus in immunoassay detection of kidney collecting duct biomarkers. Biomarkers 15(5), pp. 424-435. (10.3109/1354750X.2010.483526)
Price, S. A. et al. 2010. Characterization of Renal Papillary Antigen 1 (RPA-1), a Biomarker of Renal Papillary Necrosis. Toxicologic Pathology 38(3), pp. 346-358. (10.1177/0192623310362246)
Telezhkin, V., Brazier, S. P., Cayzac, S. H., Wilkinson, W. J., Riccardi, D. and Kemp, P. J. 2010. Mechanism of inhibition by hydrogen sulfide of native and recombinant BKCa channels. Respiratory Physiology & Neurobiology 172(3), pp. 169-178. (10.1016/j.resp.2010.05.016)
Riccardi, D. and Brown, E. M. 2010. Physiology and pathophysiology of the calcium-sensing receptor in the kidney. American Journal of Physiology-Renal Physiology 298(3), pp. F485-F499. (10.1152/ajprenal.00608.2009.)
Warburton, D. et al. 2010. Lung organogenesis. Current Topics in Developmental Biology 90, pp. 73-158. (10.1016/S0070-2153(10)90003-3)

2009

Wilkinson, W. J., Gadeberg, H., Harrison, A. W. J., Allen, N. D., Riccardi, D. and Kemp, P. J. 2009. Carbon monoxide is a rapid modulator of recombinant and native P2X(2) ligand-gated ion channels. British Journal of Pharmacology 158(3), pp. 862-871. (10.1111/j.1476-5381.2009.00354.x)
Kemp, P. J. et al. 2009. Enzyme-linked oxygen sensing by potassium channels. Annals of the New York Academy of Sciences 1177, pp. 112-118. (10.1111/j.1749-6632.2009.05025.x)
Topala, C., Schoeber, J., Searchfield, L., Riccardi, D., Hoenderop, J. and Bindels, R. 2009. Activation of the Ca2+-sensing receptor stimulates the activity of the epithelial Ca2+ channel TRPV5. Cell Calcium 45(4), pp. 331-339. (10.1016/j.ceca.2008.12.003)
Brazier, S. P., Telezhkin, V., Mears, R., Müller, T., Riccardi, D. and Kemp, P. J. 2009. Cysteine residues in the C-terminal tail of the human BKCaα subunit are important for channel sensitivity to carbon monoxide. Presented at: International Society of Arterial Chemoreception. 17th Meeting, Valladolid, Spain, 1-5 July 2008Arterial Chemoreceptors. Advances in Experimental Medicine and Biology Vol. 648. Netherlands: Springer Netherlands pp. 49-56., (10.1007/978-90-481-2259-2_5)
Alam, M. et al. 2009. Calcification is associated with loss of functional calcium-sensing receptor in vascular smooth muscle cells. Cardiovascular Research 81(2), pp. 260-268. (10.1093/cvr/cvn279)
Topala, C., Schoeber, J. P. H., Searchfield, L., Riccardi, D., Hoenderop, J. G. J. and Bindels, R. J. M. 2009. Activation of the Ca2+-sensing receptor stimulates the activity of the epithelial Ca2+ channel TRPV5. Cell Calcium 45(4), pp. 331-339.
Riccardi, D., Finney, B. A., Wilkinson, W. J. and Kemp, P. J. 2009. Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR. Pflugers Archiv-European Journal of Physiology 458(6), pp. 1007-1022. (10.1007/s00424-009-0681-z)
De Proost, I. et al. 2009. Purinergic signaling in the pulmonary neuroepithelial body microenvironment unraveled by live cell imaging. The FASEB Journal 23(4), pp. 1153-1160. (10.1096/fj.08-109579)
Telezhin, V., Brazier, S. P., Cayzac, S., Müller, C. T., Riccardi, D. and Kemp, P. J. 2009. Hydrogen Sulfide inhibits human BKCa channels. Advances in Experimental Medicine and Biology 648, pp. 65-72. (10.1007/978-90-481-2259-2_7)
Cayzac, S., Rocher, A., Obeso, A., Gonzalez, C., Kemp, P. J. and Riccardi, D. 2009. Effects of the polyamine spermine on arterial chemoreception. Presented at: International Society of Arterial Chemoreception. 17th Meeting, Valladolid, Spain, 1-5 July 2008 Presented at Gonzalez, C., Nurse, C. A. and Peers, C. eds.Arterial chemoreceptors. Advances in Experimental Medicine and Biology Vol. 648. Netherlands: Springer Netherlands pp. 97-104., (10.1007/978-90-481-2259-2_11)

2008

Finney, B. et al. 2008. Regulation of mouse lung development by the extracellular calcium-sensing receptor, CaR. Journal of Physiology 586(24), pp. 6007-6019. (10.1113/jphysiol.2008.161687)
De Proost, I. et al. 2008. Functional live cell imaging of the pulmonary neuroepithelial body microenvironment. American Journal of Respiratory Cell and Molecular Biology 39(2), pp. 180-189. (10.1165/rcmb.2008-0011OC)
Williams, S. E., Brazier, S. P., Baban, N., Telezhkin, V., Muller, C. T., Riccardi, D. and Kemp, P. J. 2008. A structural motif in the C-terminal tail of slo1 confers carbon monoxide sensitivity to human BKCa channels. Pflugers Archiv-European Journal of Physiology 456(3), pp. 561-572. (10.1007/s00424-007-0439-4)
Vizard, T. N., O'Keeffe, G. W., Gutierrez, H., Kos, C. H., Riccardi, D. and Davies, A. M. 2008. Regulation of axonal and dendritic growth by the extracellular calcium-sensing receptor. Nature Neuroscience 11(3), pp. 285-291. (10.1038/nn2044)
Gibbons, C. E., Maldonado-Perez, D., Shah, A. N., Riccardi, D. and Ward, D. T. 2008. Calcium-sensing receptor antagonism or lithium treatment ameliorates aminoglycoside-induced cell death in renal epithelial cells. Biochimica et Biophysica Acta - Molecular Basis of Disease 1782(3), pp. 188-195. (10.1016/j.bbadis.2008.01.003)
Riccardi, D. and Martin, D. 2008. The role of the calcium-sensing receptor in the pathophysiology of secondary hyperparathyroidism. NDT Plus 1(Suppl.), pp. i7-i11. (10.1093/ndtplus/sfm038)
Timmermans, J. P. et al. 2008. Expression of P2X receptors in LAD-2 cells and human lung mast cells [Abstract]. Purinergic Signalling 4(S1), pp. S159. (10.1007/s11302-008-9116-0)
Wilkinson, W. J., Hanne, G., Harrison, A. W. J., Allen, N. D., Riccardi, D. and Kemp, P. J. 2008. Carbon monoxide is a rapid modulator of recombinant and native P2X2 ligand-gated ion channels [Abstract]. Purinergic Signalling 4(S1), pp. 26. (10.1007/s11302-008-9116-0)
Gamba, G. and Riccardi, D. 2008. Cell biology of thiazide bone effects. Presented at: 2nd International Urolithiasis Research Symposium, Indianapolis, IN, USA, 17-18 April 2008 Presented at Evan, A. P. et al. eds.Renal Stone Disease 2: 2nd International Urolithiasis Research Symposium, Indianapolis, Indiana, 17-18 April 2008. AIP Conference Proceedings Vol. 1049. New York: American Institute of Physics pp. 44-52., (10.1063/1.2998060)

2007

Dvorak, M. M. et al. 2007. Thiazide Diuretics Directly Induce Osteoblast Differentiation and Mineralized Nodule Formation by Interacting with a Sodium Chloride Co-Transporter in Bone. Journal of the American Society of Nephrology 18(9), pp. 2509-2516. (10.1681/ASN.2007030348)
Lu, W., Worthington, J., Riccardi, D., Balment, R. J. and McCrohan, C. R. 2007. Seasonal changes in peptide, receptor and ion channel mRNA expression in the caudal neurosecretory system of the European flounder (Platichthys flesus). General and Comparative Endocrinology 153(1-3), pp. 262-272. (10.1016/j.ygcen.2007.05.004)

2006

Lu, W. et al. 2006. Molecular characterization and expression of Urotensin II and its receptor in the flounder (Platichthys flesus): A hormone system supporting body fluid homeostasis in euryhaline fish. Endocrinology 147(8), pp. 3692-3708. (10.1210/en.2005-1457)
Kemp, P. J., Williams, S. E., Mason, H. S., Wootton, P., Iles, D. E., Riccardi, D. and Peers, C. 2006. Functional proteomics of BK potassium channels: Defining the acute oxygen sensor. In: Chadwick, D. J. and Goode, J. eds. Signalling Pathways in Acute Oxygen Sensing: Novartis Foundation Symposium 272. Novartis Foundation Symposia Wiley-Blackwell, pp. 141-151., (10.1002/9780470035009.ch12)
Kemp, P. J., Peers, C., Riccardi, D., Iles, D. E., Mason, H. S., Wootton, P. and Williams, S. E. 2006. In search of the acute oxygen sensor: Functional proteomics and acute regulation of large-conductance, calcium-activated potassium channels by hemeoxygenase-2. In: Hayashida, Y., Gonzalez, C. and Kondo, H. eds. The Arterial Chemoreceptors., Vol. 580. Advances in Experimental Medicine and Biology Springer, pp. 137-146., (10.1007/0-387-31311-7_21)
Kemp, P. J., Williams, S. E. J., Mason, H. S., Wootton, P., Iles, D. E., Riccardi, D. and Peers, C. 2006. General discussion II. Novartis Foundation Symposium(272), pp. 131-140.

2005

Ward, D. T., Maldonado-Perez, D., Hollins, L. and Riccardi, D. 2005. Aminoglycosides induce acute cell signaling and chronic cell death in renal cells that express the calcium-sensing receptor. Journal of the American Society of Nephrology 16(5), pp. 1236-1244. (10.1681/ASN.2004080631)
Ward, D. T., Hamilton, K., Burnand, R., Smith, C. P., Tomlinson, D. R. and Riccardi, D. 2005. Altered expression of iron transport proteins in streptozotocin-induced diabetic rat kidney. Biochimica et Biophysica Acta - Molecular Basis of Disease 1740(1), pp. 79-84. (10.1016/j.bbadis.2005.01.008)
Maldonado-Perez, D. and Riccardi, D. 2005. The calcium-sensing receptor as a nutrient sensor [RETRACTED]. Biochemical Society Transactions 33(1), pp. 316-320. (10.1042/BST0330316)

2004

Williams, S. E. J. et al. 2004. Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel. Science, pp. 2993-2997. (10.1126/science.1105010)
Dvorak, M. M., Siddiqua, A., Ward, D. T., Carter, D. H., Dallas, S. L., Nemeth, E. F. and Riccardi, D. 2004. Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones.. Proceedings of the National Academy of Sciences of the USA 101(14), pp. 5140-5145. (10.1073/pnas.0306141101)
Lu, W. et al. 2004. Coexpression of corticotropin-releasing hormone and urotensin I precursor genes in the caudal neurosecretory system of the Euryhaline flounder (Platichthys flesus): A possible shared role in peripheral regulation. Endocrinology 145(12), pp. 5786-5797. (10.1210/en.2004-0144)
Procino, G. et al. 2004. Extracellular calcium antagonizes forskolin-induced aquaporin 2 trafficking in collecting duct cells. Kidney International 66(6), pp. 2245-2255. (10.1111/j.1523-1755.2004.66036.x)
Brierley, M. J., Bauer, C. S., Lu, W., Riccardi, D., Balment, R. J. and McCrohan, C. R. 2004. Voltage- and Ca2+-dependent burst generation in neuroendocrine dahlgren cells in the teleost platichthys flesus. Journal of Neuroendocrinology 16(10), pp. 832-841. (10.1111/j.1365-2826.2004.01238.x)
Moreno, E. et al. 2004. A single nucleotide polymorphism alters the activity of the renal Na+:Cl- cotransporter and reveals a role for transmembrane segment 4 in chloride and thiazide affinity. Journal of Biological Chemistry 279(16), pp. 16553-16560. (10.1074/jbc.M400602200)
Dvorak, M. M. and Riccardi, D. 2004. Ca2+ as an extracellular signal in bone. Cell Calcium 35(3), pp. 249-255. (10.1016/j.ceca.2003.10.014)
Riccardi, D. 2004. The role of extracellular calcium in the regulation of intracellular calcium and cell function (II). Some answers and more questions. Cell Calcium 35(3), pp. 179-181. (10.1016/j.ceca.2003.10.007)

2003

Maldonado-Pérez, D., Breitwieser, G. E., Gama, L., Elliott, A. C., Ward, D. T. and Riccardi, D. 2003. Human calcium-sensing receptor can be suppressed by antisense sequences. Biochemical and Biophysical Research Communications 311(3), pp. 610-617. (10.1016/j.bbrc.2003.10.041)
Brierley, M. J. et al. 2003. Electrical activity of caudal neurosecretory neurons in seawater- and freshwater-adapted flounder: responses to cholinergic agonists. Journal of Experimental Biology 206(22), pp. 4011-4020. (10.1242/jeb.00631)
Ferguson, C. J. et al. 2003. Iron handling and gene expression of the divalent metal transporter, DMT1, in the kidney of the anemic Belgrade (b) rat. Kidney International 64(5), pp. 1755-1764. (10.1046/j.1523-1755.2003.00274.x)
Wareing, M. et al. 2003. Altered dietary iron intake is a strong modulator of renal DMT1 expression. American Journal of Physiology-Renal Physiology 285(6), pp. F1050-F1059. (10.1152/ajprenal.00064.2003)

2002

Riccardi, D. 2002. Wellcome prize lecture cell surface, ion-sensing receptors. Experimental Physiology 87(4), pp. 403-411. (10.1111/j.1469-445X.2002.tb00053.x)
Ward, D. T., McLarnon, S. J. and Riccardi, D. 2002. Aminoglycosides increase intracellular calcium levels and ERK activity in proximal tubular OK cells expressing the extracellular calcium-sensing receptor. Journal of the American Society of Nephrology, pp. 1481-1489. (10.1097/01.ASN.0000015623.73739.B8)
McLarnon, S. J., Holden, D., Ward, D. T., Jones, M. N., Elliott, A. C. and Riccardi, D. 2002. Aminoglycoside antibiotics induce pH-sensitive activation of the calcium-sensing receptor. Biochemical and Biophysical Research Communications 297(1), pp. 71-77. (10.1016/S0006-291X(02)02133-2)
Konstas, A. A. et al. 2002. Regulation of the epithelial sodium channel by N4WBP5A, a novel Nedd4/Nedd4-2-interacting protein. Journal of Biological Chemistry 277(33), pp. 29406-29416. (10.1074/jbc.M203018200)
McLarnon, S. J. and Riccardi, D. 2002. Physiological and pharmacological agonists of the extracellular Ca2+-sensing receptor. European Journal of Pharmacology 447(2-3), pp. 271-278. (10.1016/S0014-2999(02)01849-6)
Ward, D. and Riccardi, D. 2002. Renal physiology of the extracellular calcium-sensing receptor. Pflugers Archiv European Journal of Physiology 445(2), pp. 169-176. (10.1007/s00424-002-0914-x)

2001

Ferguson, C. J., Wareing, M., Ward, D. T., Green, R., Smith, C. P. and Riccardi, D. 2001. Cellular localization of divalent metal transporter DMT-1 in rat kidney. American Journal of Physiology-Renal Physiology 280(5), pp. F803-F814.
Ward, D. T., Yau, S. K., Mee, A. P., Mawer, E. B., Miller, C. A., Garland, H. O. and Riccardi, D. 2001. Functional, molecular, and biochemical characterization of streptozotocin-induced diabetes. Journal of the American Society of Nephrology 12(4), pp. 779-790.

2000

Wareing, M., Ferguson, C. J., Green, R., Riccardi, D. and Smith, C. P. 2000. In vivo characterization of renal iron transport in the anaesthetized rat. The Journal of Physiology 524(2), pp. 581-586. (10.1111/j.1469-7793.2000.00581.x)
Riccardi, D., Traebert, M., Ward, D. T., Kaissling, B., Biber, J., Hebert, S. C. and Murer, H. 2000. Dietary phosphate and parathyroid hormone alter the expression of the calcium-sensing receptor (CaR) and the Na + -dependent P i transporter (NaPi-2) in the rat proximal tubule. Pflugers Archiv European Journal of Physiology 441(2-3), pp. 379-387. (10.1007/s004240000436)
Riccardi, D. 2000. Calcium ions as extracellular, first messengers. Zeitschrift fur Kardiologie -Supplement- 89(Supp 2), pp. 9-14.

Module contributor: BI2331 Physiology
Module contributor: BI3355 Advances in Physiology and Pathophysiology

Research goal: to develop CaSR antagonists, calcilytics, as novel therapeutics for pulmonary diseases such as asthma, COPD and pulmonary fibrosis

Asthma remains incurable, a major and increasing cause of global suffering and premature death and affects 340 million people worldwide. Current standard asthma therapy is palliative and 5-10% of asthma sufferers do not respond to any treatment at all. What is needed is a new approach to asthma therapy which is safe, that targets the underlying cause of the disease and that prevents environmentally-induced asthma exacerbations. During asthma, the expression of certain polycations such as eosinophil cationic protein, major basic protein, spermine and spermidine) and of polyamines such as poly-L-arginine is increased. We have made the discovery that the CaSR is expressed in the airways, where activation of this receptor by polycations and polyamines drives airways hyperreactivity, bronchoconstriction and inflammation in allergic asthma (Figure 1). Excitingly, blocking the CaSR using calcilytics, we could prevent all of these effects (Yarova et al, 2015). Recently we have also shown that inhaled calcilytics suppress inflammation as well as the current standard-of-care, inhaled corticosteroids, but they also suppress airway hyperresponsiveness and remodelling while corticosteroids do not (Yarova et al, JPET 2020)(Figure 2).

Recently my laboratory has also made the discovery that the CaSR can also be activated by chemicals contained in cigarette smoke and car fumes, and by urban particulate matter (Mansfield et al, 2019)(Figure 3), strongly implicating the CaSR in the development of currently untreatable diseases such as COPD (smoker’s cough) and idiopathic pulmonary fibrosis (Wolffs et al, 2020).

Oral calcilytics were initially developed as an anti-osteoporosis drug. While they were safe and well-tolerated in patients, their development was terminated due to lack of efficacy for this indication. Our goal is repurpose existing calcilytics, delivered topically to the lung, as novel therapeutics to treat inflammatory lung disorders in people. In addition, in collaboration with Prof Andrea Brancale (Cardiff School of Pharmacy), we are also developing entirely novel calcilytics with an optimal lung delivery profile for the treatment of lung disease.

Patent: WO2014049351 Calcium/cation-sensing receptor (casr) antagonist like nps89636 for use in treating inflammatory lung disorders (asthma or copd)

References:

Yarova et al. Sci Trans Med 284, ra60, 2015 (doi: 10.1126/scitranslmed.aaa0282)
Yarova et al., JPET 2020 (DOI: https://doi.org/10.1124/jpet.120.000281
Mansfield et al.,Eur Resp J 2019; 54: Suppl. 63, PA2401
Wolffs et al: https://www.medrxiv.org/content/10.1101/2020.03.12.20034751v1
https://patents.google.com/patent/WO2014049351A1/en

Collaborators

National

Profs A Brancale, K Broadley, B Hope-Gill, G Taylor, Drs EJ Kidd, WR Ford, B Kariuki, (Cardiff);
Prof K Lewis (Swansea University and Respiratory Innovation Wales);
Prof L Mur (Aberystwyth University);
Profs CJ Corrigan, JPT Ward, C Page and C Hawrylowicz (King's College London)
Prof D Thickett (Birmingham University)
Dr DT Ward (Manchester University)

International

Prof E Kallay, Dr M Schepelmann (Vienna University)
Dr I Ellinger, R Ecker (TissueGnostics, Vienna)
Dr W Chang (UCSF, USA)
Prof G Gamba, Mexico City (UNAM)
Prof YS Prakash and C Pabelick (Mayo Clinic, Rochester, USA)
Dr M Ranieri, Prof G Valenti (University of Bari, Italy)
Prof S Ying (CMU, China)

Work funded by

Asthma UK, King's Commercialisation Institute, The Live Sciences Research Network, Marie Curie ITN “Multifaceted CaSR” and Marie Curie ETN “CaSR Biomedicine", KESS2 studentship, the Saunders Legacy Research Fund

Active research grants

Marie Curie ETN "Biomedicine"
KESS2 studentship

Role of the calcium-sensing recepto in inflammatory lung disease
Novel therapies for asthma, chronic obstructve pulmonary disease and pulmonary fibrosis
Mechanisms of pathological vascular calcification
Calcium-sensing receptor-based therapeutics for pulmonary disease

Past projects

All my PhD students have graduated successfully and on time. Here is a list of PhD students I have supervised in the last 5 years:

Main supervisor :

Ping Huang - (Marie Cure ETN "CaSR Biomedicine" - Developing CaSR-based therapeutics, calcilytics, for steroid-resistant asthma (2016-2019)
Bethan Mansfield (KESS2 PhD student) - Development of calcilytics for inflammatory lung disease (2018-current)
Kasope Wolffs - Role of the calcium-sensing receptor in the development of pulmonary fibrosis (2017-current)
Richard Bruce - Role of the calcium-sensing receptor in pulmonary remodelling (2017-current)
Petar Popov (Masters student)

Professor Daniela Riccardi

Overview

Useful links

Biography

Honours and awards

Professional memberships

Academic positions

Speaking engagements

Committees and reviewing

Publications

2022

2021

2020

2019

2018

2017

2016