Professor Arthur Conigrave
School of Life and Environmental Sciences
Professor Emeritus Arthur Conigrave (MD PhD FRACP FRSN) is an Endocrinologist specialising in the management of patients with metabolic bone disease (including osteoporosis and disorders of calcium metabolism), and a researcher in molecular endocrinology and metabolism. He has a special interest in the manner in which the body senses nutrients, particularly the macronutrients protein and carbohydrate, and two key mineral ions, calcium and phosphate. He is an expert on Calcium Sensing Receptor (CaSR) signaling mechanisms and accurately predicted that the CaSR mediates L-amino acid-induced release of important gut hormones. He is past Chair of the NHMRC Grant Review Panel in Musculoskeletal Medicine, former Dean of Sydney Medical School, and a two-time winner of the Lilly Endocrinology Research Awards.
Our research focuses on the mechanisms that underpin nutrient sensing in the body. This includes macronutrients such as protein and their constituent amino acids, and key micronutrients such as calcium and inorganic phosphate. We study the mechanisms by which dietary nutrients are detected, and how appetite responses are prioritised and coordinated. The role of FGF21 in modulating dietary protein appetite and in selection between protein- and carbohydrate-rich food sources is one key area of concern. We also study class C G-protein coupled receptors for amino acids and divalent cations, some of which, such as the calcium-sensing receptor, whose canonical ligand binding site is occupied by L-amino acids, respond to more than one class of nutrient, depending on the composition of the local environment.
Publications
Book Chapters
- Quinn, S., Conigrave, A. (2003). Alternative agonists and modulators: evidence that the calcium-sensing receptor is a multi-modal sensor. In Chattopadhyay, Naibedya; Brown, Edward M (Eds.), Calcium-sensing Receptor, (pp. 203-226). Germany: Springer.
Journals
- Zaman, K., Mun, H., Solon-Biet, S., Senior, A., Raubenheimer, D., Simpson, S., Conigrave, A. (2024). Mice Regulate Dietary Amino Acid Balance and Energy Intake by Selecting between Complementary Protein Sources. The Journal of Nutrition, 154(6), 1766-1780. [More Information]
- Zuo, H., Wang, L., Mendez, J., Eng, E., Zhang, Z., Lin, X., Grassucci, R., Hendrickson, W., Clarke, O., Javitch, J., Conigrave, A., et al (2024). Promiscuous G-protein activation by the calcium-sensing receptor. Nature, 629(8011), 481-488. [More Information]
- Bränström, R., Vukojević, V., Lu, M., Shabo, I., Mun, H., Conigrave, A., Farnebo, L., Larsson, C. (2023). Ca2+-activated K+ channels modulate membrane potential in the human parathyroid cell: Possible role in exocytosis. Experimental Cell Research, 433(2), 113858. [More Information]
Conferences
- Conigrave, A., Lok, H., Mun, H. (2007). Effects of specific amino acids on the calcium sensor. 6th Symposium on Nutritional Aspects of Osteoporosis 2006, United States: Elsevier.
- Brennan-Speranza, T., Rybchyn, M., Halbout, P., Conigrave, A., Mason, R. (2007). Strontium ranelate effects in human osteoblasts support its uncoupling effect on bone formation and bone resorption. 29th Annual Meeting American Society for Bone and Mineral Research (ASBMR), Washington DC, USA: American Society for Bone and Mineral Research.
- Mason, R., Conigrave, A., Rybchyn, M., Brennen, T. (2007). Strontium ranelate effects on bone formation and bone resorption: an in vitro in human osteoblasts. Seventh European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, Washington, DC: Springer UK.
2024
- Zaman, K., Mun, H., Solon-Biet, S., Senior, A., Raubenheimer, D., Simpson, S., Conigrave, A. (2024). Mice Regulate Dietary Amino Acid Balance and Energy Intake by Selecting between Complementary Protein Sources. The Journal of Nutrition, 154(6), 1766-1780. [More Information]
- Zuo, H., Wang, L., Mendez, J., Eng, E., Zhang, Z., Lin, X., Grassucci, R., Hendrickson, W., Clarke, O., Javitch, J., Conigrave, A., et al (2024). Promiscuous G-protein activation by the calcium-sensing receptor. Nature, 629(8011), 481-488. [More Information]
2023
- Bränström, R., Vukojević, V., Lu, M., Shabo, I., Mun, H., Conigrave, A., Farnebo, L., Larsson, C. (2023). Ca2+-activated K+ channels modulate membrane potential in the human parathyroid cell: Possible role in exocytosis. Experimental Cell Research, 433(2), 113858. [More Information]
- Conigrave, A., Simpson, S. (2023). Calcium-Sensing Receptors Mediate Amino Acid Signals From the Liver to Islet Alpha Cells. Journal of Clinical Endocrinology and Metabolism, 108(9), e893-e894. [More Information]
- Brennan, S., Mun, H., Delbridge, L., Kuchel, P., Conigrave, A. (2023). Temperature sensing by the calcium-sensing receptor. Frontiers in Physiology, 14. [More Information]
2022
- Khan, M., Brown, A., Edwards, K., Gregory, K., Leach, K., Conigrave, A. (2022). Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects Ca2+ Sensing but Not G Protein Interaction. Journal of Bone and Mineral Research, 37(9), 1787-1807. [More Information]
- Josephs, T., Zhang, F., Dinh, L., Keller, A., Conigrave, A., Capuano, B., Gregory, K., Leach, K. (2022). Personalised medicines for familial hypercalcemia and hyperparathyroidism. Journal of Molecular Endocrinology, 69(1), 243-257. [More Information]
- Yang, C., Rybchyn, M., De Silva, W., Matthews, J., Holland, A., Conigrave, A., Mason, R. (2022). UV-induced DNA Damage in Skin is Reduced by CaSR Inhibition. Photochemistry and Photobiology, 98(5), 1157-1166. [More Information]
2021
- Huang, A., Binmahfouz, L., Hancock, D., Anderson, P., Ward, D., Conigrave, A. (2021). Calcium-Sensing Receptors Control CYP27B1-Luciferase Expression: Transcriptional and Posttranscriptional Mechanisms. Journal of the Endocrine Society, 5(9), bvab057. [More Information]
- Park, J., Zuo, H., Frangaj, A., Fu, Z., Yen, L., Zhang, Z., Mosyak, L., Slavkovich, V., Liu, J., Ray, K., Conigrave, A., et al (2021). Symmetric activation and modulation of the human calcium-sensing receptor. Proceedings of the National Academy of Sciences of the United States of America, 118(51), e2115849118. [More Information]
- Rybchyn, M., Brennan-Speranza, T., Mor, D., Cheng, Z., Chang, W., Conigrave, A., Mason, R. (2021). The mTORC2 Regulator Homer1 Modulates Protein Levels and Sub-Cellular Localization of the CaSR in Osteoblast-Lineage Cells. International Journal of Molecular Sciences, 22(12), 6509-1-6509-12. [More Information]
2020
- Leach, K., Hannan, F., Josephs, T., Keller, A., Møller, T., Ward, D., Kallay, E., Mason, R., Thakker, R., Riccardi, D., Conigrave, A., et al (2020). International union of basic and clinical pharmacology. CVIII. calcium-sensing receptor nomenclature, pharmacology, and function. Pharmacological Reviews, 72(3), 558-604. [More Information]
- Josephs, T., Keller, A., Khajehali, E., DeBono, A., Langmead, C., Conigrave, A., Capuano, B., Kufareva, I., Gregory, K., Leach, K. (2020). Negative allosteric modulators of the human calcium-sensing receptor bind to overlapping and distinct sites within the 7-transmembrane domain. British Journal of Pharmacology, 177(8), 1917-1930. [More Information]
2019
- Fayet, F., Brock, K., Wright, J., Ridges, L., Small, P., Seibel, M., Conigrave, A., Mason, R. (2019). Determinants of vitamin D status of healthy office workers in Sydney, Australia. Journal of Steroid Biochemistry and Molecular Biology, 189, 127-134. [More Information]
- Rybchyn, M., Islam, K., Brennan-Speranza, T., Cheng, Z., Brennan, S., Chang, W., Mason, R., Conigrave, A. (2019). Homer1 mediates CaSR-dependent activation of mTOR complex 2 and initiates a novel pathway for AKT-dependent beta-catenin stabilization in osteoblasts. Journal of Biological Chemistry, 294(44), 16337-16350. [More Information]
- Binmahfouz, L., Centeno, P., Conigrave, A., Ward, D. (2019). Identification of Serine-875 as an Inhibitory Phosphorylation Site in the Calcium-Sensing Receptor. Molecular Pharmacology, 96(2), 204-211. [More Information]
2018
- Gregory, K., Kufareva, I., Keller, A., Khajehali, E., Mun, H., Goolam, M., Mason, R., Capuano, B., Conigrave, A., Christopoulos, A., et al (2018). Dual Action Calcium-Sensing Receptor Modulator Unmasks Novel Mode-Switching Mechanism. Journal of the American Chemical Society, 1(2), 96-109. [More Information]
- Keller, A., Kufareva, I., Josephs, T., Diao, J., Mai, V., Conigrave, A., Christopoulos, A., Gregory, K., Leach, K. (2018). Identification of Global and Ligand-Specific Calcium Sensing Receptor Activation Mechanisms. Molecular Pharmacology, 93(6), 619-630. [More Information]
- Ward, B., Rea, S., Magno, A., Pedersen, B., Brown, S., Mullin, S., Arulpragasam, A., Ingley, E., Conigrave, A., Ratajczak, T. (2018). The endoplasmic reticulum-associated protein, OS-9, behaves as a lectin in targeting the immature calcium-sensing receptor. Journal of Cellular Physiology, 233(1), 38-56. [More Information]
2016
- Solon-Biet, S., Cogger, V., Pulpitel, T., Heblinski, M., Wahl, D., McMahon, A., Warren, A., Durrant-Whyte, J., Walters, K., Krycer, J., Ponton, F., Gokarn, R., Wali, J., Conigrave, A., James, D., Raubenheimer, D., Le Couteur, D., Simpson, S., et al (2016). Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework. Cell Metabolism, 24(4), 555-565. [More Information]
- Gosby, A., Lau, N., Tam, C., Iglesias, M., Morrison, C., Caterson, I., Brand-Miller, J., Conigrave, A., Raubenheimer, D., Simpson, S. (2016). Raised FGF-21 and Triglycerides Accompany Increased Energy Intake Driven by Protein Leverage in Lean, Healthy Individuals: A Randomised Trial. PloS One, 11(8), 1-16. [More Information]
- Geng, Y., Mosyak, L., Kurinov, I., Zuo, H., Sturchler, E., Cheng, T., Subramanyam, P., Brown, A., Brennan, S., Mun, H., Conigrave, A., et al (2016). Structural mechanism of ligand activation in human calcium-sensing receptor. eLife, 5, 1-25. [More Information]
2015
- Cook, A., Mistry, S., Gregory, K., Furness, S., Sexton, P., Scammells, P., Conigrave, A., Christopoulos, A., Leach, K. (2015). Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics. British Journal of Pharmacology, 172(1), 185-200. [More Information]
- Brennan-Speranza, T., Conigrave, A. (2015). Osteocalcin: An osteoblast-derived polypeptide hormone that modulates whole body energy metabolism. Calcified Tissue International, 96(1), 1-10. [More Information]
- Campion, K., McCormick, W., Warwicker, J., Bin Khayat, M., Atkinson-Dell, R., Steward, M., Delbridge, L., Mun, H., Conigrave, A., Ward, D. (2015). Pathophysiologic changes in extracellular pH modulate parathyroid calcium-sensing receptor activity and secretion via a histidine-independent mechanism. Journal of the American Society of Nephrology, 26(9), 2163-2171. [More Information]
2014
- Leach, K., Sexton, P., Christopoulos, A., Conigrave, A. (2014). Engendering biased signalling from the calcium-sensing receptor for the pharmacotherapy of diverse disorders. British Journal of Pharmacology, 171(5), 1142-1155. [More Information]
- Ujvari, B., Mun, H., Conigrave, A., Ciofi, C., Madsen, T. (2014). Invasive toxic prey may imperil the survival of an iconic giant lizard, the Komodo dragon. Pacific Conservation Biology, 20(4), 363-365. [More Information]
- Puckeridge, M., Chapman, B., Conigrave, A., Kuchel, P. (2014). Membrane flickering of the human erythrocyte: physical and chemical effectors. European Biophysics Journal, 43(4-5), 169-177. [More Information]
2013
- Conigrave, A., Ward, D. (2013). Calcium-sensing receptor (CaSR): Pharmacological properties and signaling pathways. Best Practice and Research: Clinical Endocrinology and Metabolism, 27(3), 315-331. [More Information]
- Avlani, V., Ma, W., Mun, H., Leach, K., Delbridge, L., Christopoulos, A., Conigrave, A. (2013). Calcium-sensing receptor-dependent activation of CREB phosphorylation in HEK293 cells and human parathyroid cells. American Journal of Physiology - Endocrinology and Metabolism, 304(10), E1097-E1104. [More Information]
- Puckeridge, M., Chapman, B., Conigrave, A., Kuchel, P. (2013). Corrigendum to Quantitative model of NMR chemical shifts of 23Na + induced by TmDOTP: Applications in studies of Na+ transport in human erythrocytes (Journal of Inorganic Biochemistry (2012) 115 (211-219)). Journal of Inorganic Biochemistry, 121, 196.
2012
- Leach, K., Wen, A., Davey, A., Sexton, P., Conigrave, A., Christopoulos, A. (2012). Identification of Molecular Phenotypes and Biased Signaling Induced by Naturally Occurring Mutations of the Human Calcium-Sensing Receptor. Endocrinology, 153(9), 4304-4316. [More Information]
- Davey, A., Leach, K., Valant, C., Conigrave, A., Sexton, P., Christopoulos, A. (2012). Positive and Negative Allosteric Modulators Promote Biased Signaling at the Calcium-Sensing Receptor. Endocrinology, 153(3), 1232-1241. [More Information]
- Puckeridge, M., Chapman, B., Conigrave, A., Kuchel, P. (2012). Quantitative model of NMR chemical shifts of (23)Na(+) induced by TmDOTP: Applications in studies of Na(+) transport in human erythrocytes. Journal of Inorganic Biochemistry, 115, 211-219. [More Information]
2011
- Lazarus, S., Pretorius, C., Khafagi, F., Campion, K., Brennan, S., Conigrave, A., Brown, E., Ward, D. (2011). A novel mutation of the primary protein kinase C phosphorylation site in the calcium-sensing receptor causes autosomal dominant hypocalcemia. European Journal of Endocrinology, 164(3), 429-435. [More Information]
- Broadhead, G., Mun, H., Avlani, V., Jourdon, O., Church, W., Christopoulos, A., Delbridge, L., Conigrave, A. (2011). Allosteric Modulation of the Calcium-sensing Receptor by y-Glutamyl Peptides Inhibition of PTH Secretion, Suppression of Intracellular cAMP Levels and A Common Mechanism of Action with L-Amino Acids. Journal of Biological Chemistry, 286(11), 8786-8797. [More Information]
- Rybchyn, M., Slater, M., Conigrave, A., Mason, R. (2011). An Akt-dependent increase in canonical Wnt Signalling and a Decrease in Sclerostin Protein Levels Are Involved in Strontium Ranelate-induced Osteogenic Effects in Human Osteoblasts. Journal of Biological Chemistry, 286(27), 23771-23779. [More Information]
2010
- Conigrave, A., Hampson, D. (2010). Broad-spectrum amino acid-sensing class C G-protein coupled receptors: Molecular mechanisms, physiological significance and options for drug development. Pharmacology and Therapeutics, 127(3), 252-260. [More Information]
- Hannan, F., Nesbit, M., Turner, J., Stacey, J., Cianferotti, L., Christie, P., Conigrave, A., Whyte, M., Thakker, R. (2010). Comparison of human chromosome 19q13 and syntenic region on mouse chromosome 7 reveals absence, in man, of 11.6 Mb containing four mouse calcium-sensing receptor-related sequences: relevance to familial benign hypocalciuric hypercalcaemia type 3. European Journal of Human Genetics, 18(4), 442-447. [More Information]
- Gosby, A., Soares-Wynter, S., Campbell, C., Badaloo, A., Antonelli, M., Hall, R., Martinez-Cordero, C., Jebb, S., Brand-Miller, J., Caterson, I., Conigrave, A., Simpson, S., et al (2010). Design and testing of foods differing in protein to energy ratios. Appetite, 55(2), 367-370. [More Information]
2009
- Mun, H., Brennan, S., Delbridge, L., Wilkinson, M., Brown, E., Conigrave, A. (2009). Adenomatous human parathyroid cells exhibit impaired sensitivity to L-amino acids. The Journal of Clinical Endocrinology and Metabolism, 94(9), 3567-3574. [More Information]
- Szekely, D., Brennan, S., Mun, H., Conigrave, A., Kuchel, P. (2009). Effectors of the frequency of calcium oscillations in HEK-293 cells: wavelet analysis and a computer model. European Biophysics Journal, 39(1), 149-165. [More Information]
- Brennan-Speranza, T., Rybchyn, M., Green, W., Atwa, S., Conigrave, A., Mason, R. (2009). Osteoblasts play key roles in the mechanisms of action of strontium ranelate. British Journal of Pharmacology, 157, 1291-1300. [More Information]
2008
- Conigrave, A., Brown, E., Rizzoli, A. (2008). Dietary Protein and Bone Health: Roles of Amino Acid-Sensing Receptors in the Control of Calcium Metabolism and Bone Homeostasis. Annual Review of Nutrition, 28, 131-155. [More Information]
- Lu, M., Forsberg, L., Hoog, A., Juhlin, C., Vukojevic, V., Larsson, C., Conigrave, A., Delbridge, L., Gill, A., Bark, C., et al (2008). Heterogeneous expression of SNARE proteins SNAP-23, SNAP-25, Syntaxin1 and VAMP in human parathyroid tissue. Molecular And Cellular Endocrinology, 287(1-2), 72-80. [More Information]
- Au, A., McDonald, K., Gill, A., Sywak, M., Diamond, T., Conigrave, A., Clifton-Bligh, R. (2008). PTH Mutation with Primary Hyperparathyroidism and Undetectable Intact PTH. New England Journal of Medicine, 359(11), 1184-1186. [More Information]
2007
- Lee, H., Mun, H., Lewis, N., Crouch, M., Culverston, E., Mason, R., Conigrave, A. (2007). Allosteric activation of the extracellular Ca2+- sensing receptor by L-amino acids enhances ERK1/2 phosphorylation. Biochemical Journal, 404(1), 141-149. [More Information]
- Conigrave, A., Mun, H., Lok, H. (2007). Aromatic L-amino Acids activate the calcium-sensing receptor. The Journal of Nutrition, 137(Supplement), 1524S-1527S. [More Information]
- Conigrave, A., Lok, H., Mun, H. (2007). Effects of specific amino acids on the calcium sensor. 6th Symposium on Nutritional Aspects of Osteoporosis 2006, United States: Elsevier.
2006
- Conigrave, A., Hampson, D. (2006). Broad-spectrum L-amino acid sensing by class 3 G-protein-coupled receptors. Trends in Endocrinology and Metabolism, 17(10), 398-407. [More Information]
- Conigrave, A., Brown, E. (2006). Taste Receptors in the Gastrointestinal Tract II. L-Amino acid sensing by calcium-sensing receptors: implications for GI physiology. American Journal of Physiology: Gastrointestinal and Liver Physiology, 291(5), G753-G761. [More Information]
2005
- Mun, H., Culverston, E., Franks, A., Collyer, C., Clifton-Bligh, R., Conigrave, A. (2005). A double mutation in the extracellular Ca2+-sensing receptor's venus flytrap domain that selectively disables L-amino acid sensing. Journal of Biological Chemistry, 280(32), 29067-29072. [More Information]
- Brennan-Speranza, T., Muir, M., Conigrave, A., Mason, R. (2005). Is strontium anabolic?: Mechanisms of action in human osteoblasts. 15th Annual Scientific Meeting of the Australian and New Zealand Bone and Mineral Society 2005.
- Mun, H., Conigrave, A., Wilkinson, M., Delbridge, L. (2005). Surgery for hyperparathyroidism: does morphology or function matter most? Surgery, 138(6), 1111-1120. [More Information]
2004
- Conigrave, A., Lok, H. (2004). Activation Of Renal Calcium And Water Excretion By Novel Physiological And Pharmacological Activators Of The Calcium-Sensing Receptor. Clinical and Experimental Pharmacology and Physiology, 31(5), 368-371. [More Information]
- Shemon, A., Sluyter, R., Conigrave, A., Wiley, J. (2004). Chelerythrine And Other Benzophenanthridine Alkaloids Block The Human P2X(7) Receptor. British Journal of Pharmacology, 142(6), 1015-1019. [More Information]
- Brennan-Speranza, T., Muir, M., Conigrave, A., Mason, R. (2004). Functional responses of bone cells to stimulation by strontium. Australian and New Zealand Bone and Mineral Society, 14th Annual Scientific Meeting.
2003
- Conigrave, A., Franks, A. (2003). Allosteric activation of plasma membrane receptors - physiological implications and structural origins. Progress in Biophysics and Molecular Biology, 81, 219-240. [More Information]
- Quinn, S., Conigrave, A. (2003). Alternative agonists and modulators: evidence that the calcium-sensing receptor is a multi-modal sensor. In Chattopadhyay, Naibedya; Brown, Edward M (Eds.), Calcium-sensing Receptor, (pp. 203-226). Germany: Springer.
- Tan, Y., Cardinal, J., Franks, A., Mun, H., Lewis, N., Harris, L., Prins, J., Conigrave, A. (2003). Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor. The Journal of Clinical Endocrinology and Metabolism, 88(2), 605-610. [More Information]
2002
- Conigrave, A., Franks, A., Brown, E., Quinn, S. (2002). L-Amino acid sensing by the calcium-sensing receptor: a general mechanism for coupling protein and calcium metabolism? European Journal of Clinical Nutrition, 56(11), 1072-1080. [More Information]
- Bradbury, R., Cropley, J., Kifor, O., Lovicu, F., De Iongh, R., Kable, E., Brown, E., Seely, E., Peat, B., Conigrave, A. (2002). Localization of the extracellular Ca2+ -sensing receptor in the human placenta. Placenta, 23(2-3), 192-200. [More Information]
- Zhang, Z., Qiu, W., Quinn, S., Conigrave, A., Brown, E., Bai, M. (2002). Three adjacent serines in the extracellular domains of the CaR are required for L-amino acid-mediated potentiation of the receptor function. Journal of Biological Chemistry, 277(37), 33727-33735. [More Information]
2001
- Conigrave, A. (2001). Molecular mechanisms of receptor dysfunction: implications for endocrine disorders. Current Opinion in Endocrinology, Diabetes and Obesity, 8(1), 41-46. [More Information]
- Conigrave, A., Gu, B., Zhang, W., Wiley, J., Fernando, K., Tasevski, V., Luttrell, B. (2001). P2Y11 receptor expression by human lymphocytes: evidence for two cAMP-linked purinoceptors. European Journal of Pharmacology, 426, 157-163. [More Information]
Selected Grants
2017
- Towards the rational design of calcium sensing receptor allosteric modulators for the treatment of osteoporosis and calcium handling disorders, Leach K, Conigrave A, National Health and Medical Research Council (NHMRC)/Project Grants
2016
- Identifying the cellular and structural basis for skeletal fragility in Type 2 Diabetes, Brennan-Speranza T, Mason R, Conigrave A, Rebecca L Cooper Medical Research Foundation/Research Grant
- Is FGF21 the master regulator of protein intake?, Simpson S, James D, Raubenheimer D, Conigrave A, Le Couteur D, Australian Research Council (ARC)/Discovery Projects (DP)