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    Wenhan Chang

    TitleProfessor
    SchoolUCSF School of Medicine
    DepartmentMedicine
    Address4150 Clement St
    San Francisco CA 94121
    Phone415-575-0558x3880
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      My research investigates the roles of the extracellular Ca2+, insulin-like growth factor-1 (IGF1), parathyroid hormone (PTH), and vitamin D, and their respective receptors (CaSR, IGF1R, PTH1R, and VDR) in (1) controlling mineral homeostasis; (2) mediating skeletal development and facture healing; (3) regulating neuroendocrine functions; and (4) neuroprotection. We study mice with conditional knockout (KO) of genes encoding CaSR, IGF1, IGF1R, PTH1R, Cyp27b1, VDR, and their associated signaling molecules in parathyroid cells (PTC), intestinal epithelial cells, renal tubule cells, chondrocytes, bone cells, and/or neurons to determine their biological functions. These in vivo studies are complemented with in vitro cell/organ cultures of parathyroid cells/glands; primary intestinal and renal tubular cells and associated cell lines; primary chondrocyte, osteoblast, osteoclast, and related cell lines; and neurons to further delineate the underlying mechanisms. We perform union and nonunion bone fractures on the above KO mice and study the structural, biochemical, and biomechanics properties of the resulting callus to determine the functions of the CaSR, IGF1, IGF1R, PTH1R, Cyp27b1, VDR, and their associated signaling molecules in facture healing. Based on the above study, we are developing new pharmacological regimens for more robust skeletal anabolism to treat osteoporosis and repair bone. We also perform brain ischemia and traumatic brain injury protocols on the KO mice to assess the role of those molecules in the development of neuronal injury and to develop new therapies for neuroprotection against ischemia- and TBI-induced brain injury.
      Dr. Chang is also the director of the SF-VAMC Bone Imaging Core facility.


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      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Kim W, Takyar FM, Swan K, Jeong J, VanHouten J, Sullivan CA, Dann P, Yu H, Fiaschi-Taesch N, Chang W, Wysolmerski J, et al. Calcium-sensing receptor (CaSR) promotes breast cancer by stimulating intracrine actions of parathyroid hormone-related protein. Cancer Res. 2016 Jul 22. PMID: 27450451.
        View in: PubMed
      2. Joo A, Long R, Cheng Z, Alexander C, Chang W, Klein OD. Sprouty2 regulates endochondral bone formation by modulation of RTK and BMP signaling. Bone. 2016 Jul; 88:170-9. PMID: 27130872.
        View in: PubMed
      3. Al-Dujaili SA, Koh AJ, Dang M, Mi X, Chang W, Ma PX, McCauley LK. Calcium Sensing Receptor Function Supports Osteoblast Survival and Acts as a Co-Factor in PTH Anabolic Actions in Bone. J Cell Biochem. 2016 Jul; 117(7):1556-67. PMID: 26579618.
        View in: PubMed
      4. Zhang M, Wang H, Zhang J, Zhang H, Yang H, Wan X, Jing L, Lu L, Liu X, Yu S, Chang W, Wang M. Unilateral anterior crossbite induces aberrant mineral deposition in degenerative temporomandibular cartilage in rats. Osteoarthritis Cartilage. 2016 May; 24(5):921-31. PMID: 26746151.
        View in: PubMed
      5. Santa Maria C, Cheng Z, Li A, Wang J, Shoback D, Tu CL, Chang W. Interplay between CaSR and PTH1R signaling in skeletal development and osteoanabolism. Semin Cell Dev Biol. 2016 Jan; 49:11-23. PMID: 26688334.
        View in: PubMed
      6. Graca JA, Schepelmann M, Brennan SC, Reens J, Chang W, Yan P, Toka H, Riccardi D, Price SA. Comparative expression of the extracellular calcium-sensing receptor in the mouse, rat, and human kidney. Am J Physiol Renal Physiol. 2016 Mar 15; 310(6):F518-33. PMID: 26661650.
        View in: PubMed
      7. Schepelmann M, Yarova PL, Lopez-Fernandez I, Davies TS, Brennan SC, Edwards PJ, Aggarwal A, Graça J, Rietdorf K, Matchkov V, Fenton RA, Chang W, Krssak M, Stewart A, Broadley KJ, Ward DT, Price SA, Edwards DH, Kemp PJ, Riccardi D. The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure. Am J Physiol Cell Physiol. 2016 Feb 1; 310(3):C193-204. PMID: 26538090.
        View in: PubMed
      8. Bikle DD, Tahimic C, Chang W, Wang Y, Philippou A, Barton ER. Role of IGF-I signaling in muscle bone interactions. Bone. 2015 Nov; 80:79-88. PMID: 26453498; PMCID: PMC4600536 [Available on 11/01/16].
      9. Wang T, Wang Y, Menendez A, Fong C, Babey M, Tahimic CG, Cheng Z, Li A, Chang W, Bikle DD. Osteoblast-Specific Loss of IGF1R Signaling Results in Impaired Endochondral Bone Formation During Fracture Healing. J Bone Miner Res. 2015 Sep; 30(9):1572-84. PMID: 25801198.
        View in: PubMed
      10. Yarova PL, Stewart AL, Sathish V, Britt RD, Thompson MA, P Lowe AP, Freeman M, Aravamudan B, Kita H, Brennan SC, Schepelmann M, Davies T, Yung S, Cholisoh Z, Kidd EJ, Ford WR, Broadley KJ, Rietdorf K, Chang W, Bin Khayat ME, Ward DT, Corrigan CJ, T Ward JP, Kemp PJ, Pabelick CM, Prakash YS, Riccardi D. Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma. Sci Transl Med. 2015 Apr 22; 7(284):284ra60. PMID: 25904744.
        View in: PubMed
      11. Tang L, Peng M, Liu L, Chang W, Binder HJ, Cheng SX. Calcium-sensing receptor stimulates Cl(-)- and SCFA-dependent but inhibits cAMP-dependent HCO3(-) secretion in colon. Am J Physiol Gastrointest Liver Physiol. 2015 May 15; 308(10):G874-83. PMID: 25792563; PMCID: PMC4437021 [Available on 05/15/16].
      12. Aggarwal A, Prinz-Wohlgenannt M, Gröschel C, Tennakoon S, Meshcheryakova A, Chang W, Brown EM, Mechtcheriakova D, Kállay E. The calcium-sensing receptor suppresses epithelial-to-mesenchymal transition and stem cell- like phenotype in the colon. Mol Cancer. 2015; 14:61. PMID: 25879211; PMCID: PMC4405849.
      13. Yang T, Zhang J, Cao Y, Zhang M, Jing L, Jiao K, Yu S, Chang W, Chen D, Wang M. Wnt5a/Ror2 mediates temporomandibular joint subchondral bone remodeling. J Dent Res. 2015 Jun; 94(6):803-12. PMID: 25749876.
        View in: PubMed
      14. Kim JY, Ho H, Kim N, Liu J, Tu CL, Yenari MA, Chang W. Calcium-sensing receptor (CaSR) as a novel target for ischemic neuroprotection. Ann Clin Transl Neurol. 2014 Nov; 1(11):851-66. PMID: 25540800; PMCID: PMC4265057.
      15. Wang Y, Menendez A, Fong C, ElAlieh HZ, Chang W, Bikle DD. Ephrin B2/EphB4 mediates the actions of IGF-I signaling in regulating endochondral bone formation. J Bone Miner Res. 2014 Aug; 29(8):1900-13. PMID: 24677183; PMCID: PMC4108521.
      16. Akil O, Hall-Glenn F, Chang J, Li A, Chang W, Lustig LR, Alliston T, Hsiao EC. Disrupted bone remodeling leads to cochlear overgrowth and hearing loss in a mouse model of fibrous dysplasia. PLoS One. 2014; 9(5):e94989. PMID: 24788917; PMCID: PMC4006800.
      17. Onur TS, Wu R, Chu S, Chang W, Kim HT, Dang AB. Joint instability and cartilage compression in a mouse model of posttraumatic osteoarthritis. J Orthop Res. 2014 Feb; 32(2):318-23. PMID: 24167068; PMCID: PMC4462343.
      18. Wang Y, Bikle DD, Chang W. Autocrine and Paracrine Actions of IGF-I Signaling in Skeletal Development. Bone Res. 2013 Sep; 1(3):249-59. PMID: 26273506; PMCID: PMC4472106.
      19. Kim JY, Kim N, Yenari MA, Chang W. Hypothermia and pharmacological regimens that prevent overexpression and overactivity of the extracellular calcium-sensing receptor protect neurons against traumatic brain injury. J Neurotrauma. 2013 Jul 1; 30(13):1170-6. PMID: 23360235; PMCID: PMC3700438.
      20. Mamillapalli R, VanHouten J, Dann P, Bikle D, Chang W, Brown E, Wysolmerski J. Mammary-specific ablation of the calcium-sensing receptor during lactation alters maternal calcium metabolism, milk calcium transport, and neonatal calcium accrual. Endocrinology. 2013 Sep; 154(9):3031-42. PMID: 23782944; PMCID: PMC3749485.
      21. Cheng Z, Liang N, Chen TH, Li A, Santa Maria C, You M, Ho H, Song F, Bikle D, Tu C, Shoback D, Chang W. Sex and age modify biochemical and skeletal manifestations of chronic hyperparathyroidism by altering target organ responses to Ca2+ and parathyroid hormone in mice. J Bone Miner Res. 2013 May; 28(5):1087-100. PMID: 23239173; PMCID: PMC3617088.
      22. Riccardi D, Brennan SC, Chang W. The extracellular calcium-sensing receptor, CaSR, in fetal development. Best Pract Res Clin Endocrinol Metab. 2013 Jun; 27(3):443-53. PMID: 23856271; PMCID: PMC4462341.
      23. Tu CL, Crumrine DA, Man MQ, Chang W, Elalieh H, You M, Elias PM, Bikle DD. Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal differentiation and barrier function. J Invest Dermatol. 2012 Oct; 132(10):2350-9. PMID: 22622426; PMCID: PMC3434298.
      24. Dvorak-Ewell MM, Chen TH, Liang N, Garvey C, Liu B, Tu C, Chang W, Bikle DD, Shoback DM. Osteoblast extracellular Ca2+ -sensing receptor regulates bone development, mineralization, and turnover. J Bone Miner Res. 2011 Dec; 26(12):2935-47. PMID: 21956637; PMCID: PMC3222747.
      25. Rey O, Chang W, Bikle D, Rozengurt N, Young SH, Rozengurt E. Negative cross-talk between calcium-sensing receptor and ß-catenin signaling systems in colonic epithelium. J Biol Chem. 2012 Jan 6; 287(2):1158-67. PMID: 22094462; PMCID: PMC3256874.
      26. Wang Y, Cheng Z, Elalieh HZ, Nakamura E, Nguyen MT, Mackem S, Clemens TL, Bikle DD, Chang W. IGF-1R signaling in chondrocytes modulates growth plate development by interacting with the PTHrP/Ihh pathway. J Bone Miner Res. 2011 Jul; 26(7):1437-46. PMID: 21312270; PMCID: PMC3530140.
      27. Tu CL, Chang W, Bikle DD. The calcium-sensing receptor-dependent regulation of cell-cell adhesion and keratinocyte differentiation requires Rho and filamin A. J Invest Dermatol. 2011 May; 131(5):1119-28. PMID: 21209619; PMCID: PMC3078217.
      28. Dong Q, Cheng Z, Chang W, Blackman BE, Conte FA, Hu J, Shoback D, Miller WL. Naturally-occurring mutation in the calcium-sensing receptor reveals the significance of extracellular domain loop III region for class C G-protein-coupled receptor function. J Clin Endocrinol Metab. 2010 Oct; 95(10):E245-52. PMID: 20631026; PMCID: PMC3050095.
      29. Chang W, Dvorak M, Shoback D. Assessing constitutive activity of extracellular calcium-sensing receptors in vitro and in bone. Methods Enzymol. 2010; 484:253-66. PMID: 21036236; PMCID: PMC3528079.
      30. Chang W, Tu C, Chen TH, Bikle D, Shoback D. The extracellular calcium-sensing receptor (CaSR) is a critical modulator of skeletal development. Sci Signal. 2008; 1(35):ra1. PMID: 18765830; PMCID: PMC3538864.
      31. Tu CL, Chang W, Xie Z, Bikle DD. Inactivation of the calcium sensing receptor inhibits E-cadherin-mediated cell-cell adhesion and calcium-induced differentiation in human epidermal keratinocytes. J Biol Chem. 2008 Feb 8; 283(6):3519-28. PMID: 18065418.
        View in: PubMed
      32. Cheng Z, Tu C, Rodriguez L, Chen TH, Dvorak MM, Margeta M, Gassmann M, Bettler B, Shoback D, Chang W. Type B gamma-aminobutyric acid receptors modulate the function of the extracellular Ca2+-sensing receptor and cell differentiation in murine growth plate chondrocytes. Endocrinology. 2007 Oct; 148(10):4984-92. PMID: 17615148.
        View in: PubMed
      33. Chang W, Tu C, Cheng Z, Rodriguez L, Chen TH, Gassmann M, Bettler B, Margeta M, Jan LY, Shoback D. Complex formation with the Type B gamma-aminobutyric acid receptor affects the expression and signal transduction of the extracellular calcium-sensing receptor. Studies with HEK-293 cells and neurons. J Biol Chem. 2007 Aug 24; 282(34):25030-40. PMID: 17591780.
        View in: PubMed
      34. Dvorak MM, Chen TH, Orwoll B, Garvey C, Chang W, Bikle DD, Shoback DM. Constitutive activity of the osteoblast Ca2+-sensing receptor promotes loss of cancellous bone. Endocrinology. 2007 Jul; 148(7):3156-63. PMID: 17412806.
        View in: PubMed
      35. Tu CL, Chang W, Bikle DD. The role of the calcium sensing receptor in regulating intracellular calcium handling in human epidermal keratinocytes. J Invest Dermatol. 2007 May; 127(5):1074-83. PMID: 17124506.
        View in: PubMed
      36. Cheng Z, Tu C, Rodriguez L, Dvorak MM, Margeta M, Gassmann M, Bettler B, Shoback D, Chang W. WITHDRAWN: Type B gamma-aminobutyric Acid Receptors Modulate the Expression and Function of the Extracellular Ca2+-sensing Receptor in Murine Growth Plate Chondrocytes. Endocrinology. 2006 Sep 5. PMID: 16728489.
        View in: PubMed
      37. Wang Y, Nishida S, Sakata T, Elalieh HZ, Chang W, Halloran BP, Doty SB, Bikle DD. Insulin-like growth factor-I is essential for embryonic bone development. Endocrinology. 2006 Oct; 147(10):4753-61. PMID: 16857753.
        View in: PubMed
      38. Rodriguez L, Tu C, Cheng Z, Chen TH, Bikle D, Shoback D, Chang W. Expression and functional assessment of an alternatively spliced extracellular Ca2+-sensing receptor in growth plate chondrocytes. Endocrinology. 2005 Dec; 146(12):5294-303. PMID: 16166224.
        View in: PubMed
      39. Rodriguez L, Cheng Z, Chen TH, Tu C, Chang W. Extracellular calcium and parathyroid hormone-related peptide signaling modulate the pace of growth plate chondrocyte differentiation. Endocrinology. 2005 Nov; 146(11):4597-608. PMID: 16099862.
        View in: PubMed
      40. Tu CL, Chang W, Bikle DD. Phospholipase cgamma1 is required for activation of store-operated channels in human keratinocytes. J Invest Dermatol. 2005 Jan; 124(1):187-97. PMID: 15654973.
        View in: PubMed
      41. Chang W, Rodriguez L, Chen TH, Tu C, Shoback D. Extracellular Ca2+-sensing in cartilage. J Musculoskelet Neuronal Interact. 2004 Dec; 4(4):410-1. PMID: 15758285.
        View in: PubMed
      42. Loretz CA, Pollina C, Hyodo S, Takei Y, Chang W, Shoback D. cDNA cloning and functional expression of a Ca2+-sensing receptor with truncated C-terminal tail from the Mozambique tilapia (Oreochromis mossambicus). J Biol Chem. 2004 Dec 17; 279(51):53288-97. PMID: 15456780.
        View in: PubMed
      43. Chang W, Shoback D. Extracellular Ca2+-sensing receptors--an overview. Cell Calcium. 2004 Mar; 35(3):183-96. PMID: 15200142.
        View in: PubMed
      44. Komuves L, Oda Y, Tu CL, Chang WH, Ho-Pao CL, Mauro T, Bikle DD. Epidermal expression of the full-length extracellular calcium-sensing receptor is required for normal keratinocyte differentiation. J Cell Physiol. 2002 Jul; 192(1):45-54. PMID: 12115735.
        View in: PubMed
      45. Chang W, Tu C, Pratt S, Chen TH, Shoback D. Extracellular Ca(2+)-sensing receptors modulate matrix production and mineralization in chondrogenic RCJ3.1C5.18 cells. Endocrinology. 2002 Apr; 143(4):1467-74. PMID: 11897705.
        View in: PubMed
      46. Chang W, Pratt S, Chen TH, Bourguignon L, Shoback D. Amino acids in the cytoplasmic C terminus of the parathyroid Ca2+-sensing receptor mediate efficient cell-surface expression and phospholipase C activation. J Biol Chem. 2001 Nov 23; 276(47):44129-36. PMID: 11535593.
        View in: PubMed
      47. Shoback D, Chang W. Starvation amidst plenty--rickets and hypercalcemia in calcium receptor knockout mice. Endocrinology. 2001 Sep; 142(9):3733-5. PMID: 11517147.
        View in: PubMed
      48. Tu CL, Chang W, Bikle DD. The extracellular calcium-sensing receptor is required for calcium-induced differentiation in human keratinocytes. J Biol Chem. 2001 Nov 2; 276(44):41079-85. PMID: 11500521.
        View in: PubMed
      49. Chang W, Pratt SA, Chen TH, Tu CL, Mikala G, Schwartz A, Shoback D. Parathyroid cells express dihydropyridine-sensitive cation currents and L-type calcium channel subunits. Am J Physiol Endocrinol Metab. 2001 Jul; 281(1):E180-9. PMID: 11404236.
        View in: PubMed
      50. Gross C, De Baere E, Lo A, Chang W, Messiaen L. Cloning and characterization of human WDR10, a novel gene located at 3q21 encoding a WD-repeat protein that is highly expressed in pituitary and testis. DNA Cell Biol. 2001 Jan; 20(1):41-52. PMID: 11242542.
        View in: PubMed
      51. Chang W, Chen TH, Pratt S, Shoback D. Amino acids in the second and third intracellular loops of the parathyroid Ca2+-sensing receptor mediate efficient coupling to phospholipase C. J Biol Chem. 2000 Jun 30; 275(26):19955-63. PMID: 10764812.
        View in: PubMed
      52. Oda Y, Tu CL, Chang W, Crumrine D, Kömüves L, Mauro T, Elias PM, Bikle DD. The calcium sensing receptor and its alternatively spliced form in murine epidermal differentiation. J Biol Chem. 2000 Jan 14; 275(2):1183-90. PMID: 10625662.
        View in: PubMed
      53. Chang W, Pratt S, Chen TH, Shoback D. Protein kinase C activation blocks calcium receptor signaling in Xenopus laevis oocytes. Mol Cell Endocrinol. 1999 Dec 20; 158(1-2):13-23. PMID: 10630401.
        View in: PubMed
      54. Chang W, Tu C, Chen TH, Komuves L, Oda Y, Pratt SA, Miller S, Shoback D. Expression and signal transduction of calcium-sensing receptors in cartilage and bone. Endocrinology. 1999 Dec; 140(12):5883-93. PMID: 10579354.
        View in: PubMed
      55. Chang W, Tu C, Bajra R, Komuves L, Miller S, Strewler G, Shoback D. Calcium sensing in cultured chondrogenic RCJ3.1C5.18 cells. Endocrinology. 1999 Apr; 140(4):1911-9. PMID: 10098531.
        View in: PubMed
      56. Chang W, Chen TH, Pratt S, Shoback D. Regulation of extracellular calcium-activated cation currents by cAMP in parathyroid cells. Am J Physiol. 1998 Aug; 275(2 Pt 1):E213-21. PMID: 9688621.
        View in: PubMed
      57. Chang W, Pratt S, Chen TH, Nemeth E, Huang Z, Shoback D. Coupling of calcium receptors to inositol phosphate and cyclic AMP generation in mammalian cells and Xenopus laevis oocytes and immunodetection of receptor protein by region-specific antipeptide antisera. J Bone Miner Res. 1998 Apr; 13(4):570-80. PMID: 9556057.
        View in: PubMed
      58. Chang W, Chen TH, Pratt SA, Yen B, Fu M, Shoback D. Parathyroid Ca(2+)-conducting currents are modulated by muscarinic receptor agonists and antagonists. Am J Physiol. 1997 Nov; 273(5 Pt 1):E880-90. PMID: 9374672.
        View in: PubMed
      59. Chang W, Chen TH, Gardner P, Shoback D. Regulation of Ca(2+)-conducting currents in parathyroid cells by extracellular Ca(2+) and channel blockers. Am J Physiol. 1995 Nov; 269(5 Pt 1):E864-77. PMID: 7491938.
        View in: PubMed
      60. Chang W, Loretz CA. DPC blockade of transepithelial chloride absorption and single anion channels in teleost urinary bladder. Am J Physiol. 1993 Jul; 265(1 Pt 2):R66-75. PMID: 7688192.
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      61. Chang WH, Loretz CA. Identification of a stretch-activated monovalent cation channel from teleost urinary bladder cells. J Exp Zool. 1991 Sep; 259(3):304-15. PMID: 1717636.
        View in: PubMed
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