Our research focuses on molecular mechanisms that control both normal brain development and brain malformations. Starting with knowledge of a gene implicated in brain malformation in humans, we are using mouse models to unravel signaling pathways that specify the cellular architecture of the cortex. G-protein coupled receptors (GPCRs) are cell membrane proteins that orchestrate intracellular responses to external cues. We are particularly interested in a unique subfamily of GPCRs called adhesion GPCRs. Genetic studies have identified mutations in a specific adhesion GPCR, GPR56, that underlie bilateral frontoparietal polymicrogyria (BFPP)--a malformation named after the appearance of an excessive number of small folds, or gyri, on the surface of the brain (for details, see this PDF). On MRIs of patients with this condition, the cortex often appears to be comprised of an excessive number of small gyri, resulting in a scalloped appearance of the grey-white matter junction. Click to see pictures of BFPP in the human brain and learn more about GPR56. To investigate the specific tissue abnormalities underlying this disorder, we are characterizing the brains of mice lacking GPR56. We find that loss of GPR56 results in a "cobblestone-like" cortex--ectopic neuronal outgrowths on the brain surface cause it to resemble cobblestones. Studies in the cortex and cerebellum reveal that those neuronal ectopias are accompanied by disruption of the pial basement membrane, a thin layer of tissue ensheathing the surface of the brain. In parallel, we are examining how GPR56 signaling regulates myelination. Brain MRIs of patients with BFPP reveal associated myelination defects in the region of periventricular white matter. Oligodendrocytes are largely responsible for the development of myelin in those areas. It is possible that GPR56 signaling affects the interaction of oligodendrocytes and the axons and thus regulates myelination in the central nervous system. Using biochemical approaches, we are also investigating the functional domains of the GPR56 molecule, the ligand(s) that activate GPR56 and the signal transduction events that are triggered by GPR56 activation. Ultimately, we hope that our work will delineate novel signaling pathways that control the development of the mammalian brain and shed light on the underlying causes of brain malformations.


Xianhua Piao earned her M.D. from the Fourth Military Medical University in China and her PhD in Biology from the University of Toronto in Canada. Subsequently, she completed her residency in Pediatrics at NYU Medical Center and a fellowship in Newborn Medicine at Boston Children's Hospital and Harvard Medical School. Piao also participated in a postdoctoral fellowship at Harvard Medical School. Her research revealed a new genetic pathway in brain development and malformation, earning her the National Institutes of Health Clinical Investigator Award.



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  1. Zhu B, Luo R, Jin P, Li T, Oak HC, Giera S, Monk KR, Lak P, Shoichet BK, Piao X. GAIN domain-mediated cleavage is required for activation of G protein-coupled receptor 56 (GPR56) by its natural ligands and a small-molecule agonist. J Biol Chem. 2019 Dec 13; 294(50):19246-19254. View abstract
  2. Morgan RK, Anderson GR, Araç D, Aust G, Balenga N, Boucard A, Bridges JP, Engel FB, Formstone CJ, Glitsch MD, Gray RS, Hall RA, Hsiao CC, Kim HY, Knierim AB, Kusuluri DK, Leon K, Liebscher I, Piao X, Prömel S, Scholz N, Srivastava S, Thor D, Tolias KF, Ushkaryov YA, Vallon M, Van Meir EG, Vanhollebeke B, Wolfrum U, Wright KM, Monk KR, Mogha A. The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors. Ann N Y Acad Sci. 2019 Nov; 1456(1):5-25. View abstract
  3. Cauley ES, Hamed A, Mohamed IN, Elseed M, Martinez S, Yahia A, Abozar F, Abubakr R, Koko M, Elsayed L, Piao X, Salih MA, Manzini MC. Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556. Neurogenetics. 2019 05; 20(2):91-98. View abstract
  4. Folts CJ, Giera S, Li T, Piao X. Adhesion G Protein-Coupled Receptors as Drug Targets for Neurological Diseases. Trends Pharmacol Sci. 2019 04; 40(4):278-293. View abstract
  5. Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A, Walker AJ, Gergits F, Segel M, Nemesh J, Marsh SE, Saunders A, Macosko E, Ginhoux F, Chen J, Franklin RJM, Piao X, McCarroll SA, Stevens B. Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes. Immunity. 2019 01 15; 50(1):253-271.e6. View abstract
  6. Olaniru OE, Pingitore A, Giera S, Piao X, Castañera González R, Jones PM, Persaud SJ. The adhesion receptor GPR56 is activated by extracellular matrix collagen III to improve ß-cell function. Cell Mol Life Sci. 2018 Nov; 75(21):4007-4019. View abstract
  7. Giera S, Luo R, Ying Y, Ackerman SD, Jeong SJ, Stoveken HM, Folts CJ, Welsh CA, Tall GG, Stevens B, Monk KR, Piao X. Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells. Elife. 2018 05 29; 7. View abstract
  8. Ackerman SD, Luo R, Poitelon Y, Mogha A, Harty BL, D'Rozario M, Sanchez NE, Lakkaraju AKK, Gamble P, Li J, Qu J, MacEwan MR, Ray WZ, Aguzzi A, Feltri ML, Piao X, Monk KR. GPR56/ADGRG1 regulates development and maintenance of peripheral myelin. J Exp Med. 2018 03 05; 215(3):941-961. View abstract
  9. Moreno M, Pedrosa L, Paré L, Pineda E, Bejarano L, Martínez J, Balasubramaniyan V, Ezhilarasan R, Kallarackal N, Kim SH, Wang J, Audia A, Conroy S, Marin M, Ribalta T, Pujol T, Herreros A, Tortosa A, Mira H, Alonso MM, Gómez-Manzano C, Graus F, Sulman EP, Piao X, Nakano I, Prat A, Bhat KP, de la Iglesia N. GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma. Cell Rep. 2017 Nov 21; 21(8):2183-2197. View abstract
  10. Mehta P, Küspert M, Bale T, Brownstein CA, Towne MC, De Girolami U, Shi J, Beggs AH, Darras BT, Wegner M, Piao X, Agrawal PB. Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy. Muscle Nerve. 2017 05; 55(5):761-765. View abstract
  11. Mehta P, Piao X. Adhesion G-protein coupled receptors and extracellular matrix proteins: Roles in myelination and glial cell development. Dev Dyn. 2017 04; 246(4):275-284. View abstract
  12. Mogha A, Harty BL, Carlin D, Joseph J, Sanchez NE, Suter U, Piao X, Cavalli V, Monk KR. Gpr126/Adgrg6 Has Schwann Cell Autonomous and Nonautonomous Functions in Peripheral Nerve Injury and Repair. J Neurosci. 2016 12 07; 36(49):12351-12367. View abstract
  13. Salzman GS, Ackerman SD, Ding C, Koide A, Leon K, Luo R, Stoveken HM, Fernandez CG, Tall GG, Piao X, Monk KR, Koide S, Araç D. Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains. Neuron. 2016 Sep 21; 91(6):1292-1304. View abstract
  14. Langenhan T, Piao X, Monk KR. Adhesion G protein-coupled receptors in nervous system development and disease. Nat Rev Neurosci. 2016 09; 17(9):550-61. View abstract
  15. Sigoillot SM, Monk KR, Piao X, Selimi F, Harty BL. Adhesion GPCRs as Novel Actors in Neural and Glial Cell Functions: From Synaptogenesis to Myelination. Handb Exp Pharmacol. 2016; 234:275-298. View abstract
  16. Chen P, Piao X, Bonaldo P. Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury. Acta Neuropathol. 2015 Nov; 130(5):605-18. View abstract
  17. Schöneberg T, Liebscher I, Luo R, Monk KR, Piao X. Tethered agonists: a new mechanism underlying adhesion G protein-coupled receptor activation. J Recept Signal Transduct Res. 2015 Jun; 35(3):220-3. View abstract
  18. Petersen SC, Luo R, Liebscher I, Giera S, Jeong SJ, Mogha A, Ghidinelli M, Feltri ML, Schöneberg T, Piao X, Monk KR. The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211. Neuron. 2015 Feb 18; 85(4):755-69. View abstract
  19. Rao TN, Marks-Bluth J, Sullivan J, Gupta MK, Chandrakanthan V, Fitch SR, Ottersbach K, Jang YC, Piao X, Kulkarni RN, Serwold T, Pimanda JE, Wagers AJ. High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice. Stem Cell Res. 2015 May; 14(3):307-22. View abstract
  20. Ackerman SD, Garcia C, Piao X, Gutmann DH, Monk KR. The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Ga12/13 and RhoA. Nat Commun. 2015 Jan 21; 6:6122. View abstract
  21. Giera S, Deng Y, Luo R, Ackerman SD, Mogha A, Monk KR, Ying Y, Jeong SJ, Makinodan M, Bialas AR, Chang BS, Stevens B, Corfas G, Piao X. The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development. Nat Commun. 2015 Jan 21; 6:6121. View abstract
  22. Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B, Krishnan A, Liebscher I, Lin HH, Martinelli DC, Monk KR, Peeters MC, Piao X, Prömel S, Schöneberg T, Schwartz TW, Singer K, Stacey M, Ushkaryov YA, Vallon M, Wolfrum U, Wright MW, Xu L, Langenhan T, Schiöth HB. International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol Rev. 2015; 67(2):338-67. View abstract
  23. Liebscher I, Ackley B, Araç D, Ariestanti DM, Aust G, Bae BI, Bista BR, Bridges JP, Duman JG, Engel FB, Giera S, Goffinet AM, Hall RA, Hamann J, Hartmann N, Lin HH, Liu M, Luo R, Mogha A, Monk KR, Peeters MC, Prömel S, Ressl S, Schiöth HB, Sigoillot SM, Song H, Talbot WS, Tall GG, White JP, Wolfrum U, Xu L, Piao X. New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors. Ann N Y Acad Sci. 2014 Dec; 1333:43-64. View abstract
  24. White JP, Wrann CD, Rao RR, Nair SK, Jedrychowski MP, You JS, Martínez-Redondo V, Gygi SP, Ruas JL, Hornberger TA, Wu Z, Glass DJ, Piao X, Spiegelman BM. G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy. Proc Natl Acad Sci U S A. 2014 Nov 04; 111(44):15756-61. View abstract
  25. Luo R, Jeong SJ, Yang A, Wen M, Saslowsky DE, Lencer WI, Araç D, Piao X. Mechanism for adhesion G protein-coupled receptor GPR56-mediated RhoA activation induced by collagen III stimulation. PLoS One. 2014; 9(6):e100043. View abstract
  26. Bae BI, Tietjen I, Atabay KD, Evrony GD, Johnson MB, Asare E, Wang PP, Murayama AY, Im K, Lisgo SN, Overman L, Šestan N, Chang BS, Barkovich AJ, Grant PE, Topçu M, Politsky J, Okano H, Piao X, Walsh CA. Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning. Science. 2014 Feb 14; 343(6172):764-8. View abstract
  27. Wu MP, Doyle JR, Barry B, Beauvais A, Rozkalne A, Piao X, Lawlor MW, Kopin AS, Walsh CA, Gussoni E. G-protein coupled receptor 56 promotes myoblast fusion through serum response factor- and nuclear factor of activated T-cell-mediated signalling but is not essential for muscle development in vivo. FEBS J. 2013 Dec; 280(23):6097-113. View abstract
  28. Jeong SJ, Luo R, Singer K, Giera S, Kreidberg J, Kiyozumi D, Shimono C, Sekiguchi K, Piao X. GPR56 functions together with a3ß1 integrin in regulating cerebral cortical development. PLoS One. 2013; 8(7):e68781. View abstract
  29. Araç D, Aust G, Calebiro D, Engel FB, Formstone C, Goffinet A, Hamann J, Kittel RJ, Liebscher I, Lin HH, Monk KR, Petrenko A, Piao X, Prömel S, Schiöth HB, Schwartz TW, Stacey M, Ushkaryov YA, Wobus M, Wolfrum U, Xu L, Langenhan T. Dissecting signaling and functions of adhesion G protein-coupled receptors. Ann N Y Acad Sci. 2012 Dec; 1276:1-25. View abstract
  30. Singer K, Luo R, Jeong SJ, Piao X. GPR56 and the developing cerebral cortex: cells, matrix, and neuronal migration. Mol Neurobiol. 2013 Feb; 47(1):186-96. View abstract
  31. Jeong SJ, Luo R, Li S, Strokes N, Piao X. Characterization of G protein-coupled receptor 56 protein expression in the mouse developing neocortex. J Comp Neurol. 2012 Sep 01; 520(13):2930-40. View abstract
  32. Luo R, Jin Z, Deng Y, Strokes N, Piao X. Disease-associated mutations prevent GPR56-collagen III interaction. PLoS One. 2012; 7(1):e29818. View abstract
  33. Jeong SJ, Li S, Luo R, Strokes N, Piao X. Loss of Col3a1, the gene for Ehlers-Danlos syndrome type IV, results in neocortical dyslamination. PLoS One. 2012; 7(1):e29767. View abstract
  34. Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X. G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination. Proc Natl Acad Sci U S A. 2011 Aug 02; 108(31):12925-30. View abstract
  35. Luo R, Yang HM, Jin Z, Halley DJ, Chang BS, MacPherson L, Brueton L, Piao X. A novel GPR56 mutation causes bilateral frontoparietal polymicrogyria. Pediatr Neurol. 2011 Jul; 45(1):49-53. View abstract
  36. Strokes N, Piao X. Adhesion-GPCRs in the CNS. Adv Exp Med Biol. 2010; 706:87-97. View abstract
  37. Yang YX, Guo J, Jin Z, Yoon SY, Choi JY, Wang MH, Piao XS, Kim BW, Chae BJ. Lysine restriction and realimentation affected growth, blood profiles and expression of genes related to protein and fat metabolism in weaned pigs. J Anim Physiol Anim Nutr (Berl). 2009 Dec; 93(6):732-43. View abstract
  38. Jin Z, Luo R, Piao X. GPR56 and its related diseases. Prog Mol Biol Transl Sci. 2009; 89:1-13. View abstract
  39. Koirala S, Jin Z, Piao X, Corfas G. GPR56-regulated granule cell adhesion is essential for rostral cerebellar development. J Neurosci. 2009 Jun 10; 29(23):7439-49. View abstract
  40. Yang YX, Guo J, Yoon SY, Jin Z, Choi JY, Piao XS, Kim BW, Ohh SJ, Wang MH, Chae BJ. Early energy and protein reduction: effects on growth, blood profiles and expression of genes related to protein and fat metabolism in broilers. Br Poult Sci. 2009 Mar; 50(2):218-27. View abstract
  41. Li S, Jin Z, Koirala S, Bu L, Xu L, Hynes RO, Walsh CA, Corfas G, Piao X. GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci. 2008 May 28; 28(22):5817-26. View abstract
  42. Liu P, Piao XS, Kim SW, Wang L, Shen YB, Lee HS, Li SY. Effects of chito-oligosaccharide supplementation on the growth performance, nutrient digestibility, intestinal morphology, and fecal shedding of Escherichia coli and Lactobacillus in weaning pigs. J Anim Sci. 2008 Oct; 86(10):2609-18. View abstract
  43. Jin Z, Tietjen I, Bu L, Liu-Yesucevitz L, Gaur SK, Walsh CA, Piao X. Disease-associated mutations affect GPR56 protein trafficking and cell surface expression. Hum Mol Genet. 2007 Aug 15; 16(16):1972-85. View abstract
  44. Xianhua Piao and Christopher A. Walsh. GPR56 and Bilateral Frontoparietal Polymicrogyria. Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis. C.J. Epstein, R.P. Erickson, and A. Wynshaw-Boris eds. 2007; 1309-1312. View abstract
  45. Xianhua Piao. White Matter Injury. Primary Care of the Premature Infant. Brodsky D and Quellette MA eds. 2007. View abstract
  46. Zhaohui Jin, Ian Tietjen, Lihong Bu, Liqun Liu-Yesucevitz, Shantanu K. Gaur, Christopher A. Walsh, and Xianhua Piao. Disease-associated mutations affect intracellular traffic and function of GPR56. Pediatric Academic Societies 2007 Annual Meeting, May 3-8, 2007, Toronto, Canada. 2007. View abstract
  47. Zhaohui Jin, Ian Tietjen, Lihong Bu, Liqun Liu-Yesucevitz, Shantanu K. Gaur, Christopher A. Walsh, and Xianhua Piao. Posttranslational Modification of G Protein-coupled Receptor 56 (GPR56) is Essential for Its Function. G Protein-Coupled Receptors: Evolving Concepts and New Techniques (C1), Keystone, Colorado, February, 2006. 2006. View abstract
  48. Lihong Bu, Lei Xu, Anthony D. Hill, Liqun Liu-Yesucevitz, Richard O. Hynes, Christopher A. Walsh, and Xianhua Piao. Loss of GPR56 Function Leads to Cortical Lamination Defects. Gordon Conference—Neural Development, 2006, Salve Regina University, Newport, RI. 2006. View abstract
  49. Piao X, Chang BS, Bodell A, Woods K, Benzeev B, Topcu M, Guerrini R, Goldberg-Stern H, Sztriha L, Dobyns WB, Barkovich AJ, Walsh CA. Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes. Ann Neurol. 2005 Nov; 58(5):680-7. View abstract
  50. Xianhua Piao. The GPR56 Gene. International Symposium on Polymicrogyria Syndromes and Epilepsy. 2005. View abstract
  51. Xianhua Piao, Bernard S. Chang, Adria Bodell, Katherine Woods, BFPP clinical collaborative group, and Christopher A. Walsh. Mutations in GPR56 define classic Bilateral Frontoparietal Polymicrogyria (BFPP) syndrome. Pediatric Academic Societies 2005 Annual Meeting, Washington DC, May, 2005. 2005. View abstract
  52. Piao X, Walsh CA. A novel signaling mechanism in brain development. Pediatr Res. 2004 Sep; 56(3):309-10. View abstract
  53. Chang BS, Piao X, Giannini C, Cascino GD, Scheffer I, Woods CG, Topcu M, Tezcan K, Bodell A, Leventer RJ, Barkovich AJ, Grant PE, Walsh CA. Bilateral generalized polymicrogyria (BGP): a distinct syndrome of cortical malformation. Neurology. 2004 May 25; 62(10):1722-8. View abstract
  54. Piao X, Hill RS, Bodell A, Chang BS, Basel-Vanagaite L, Straussberg R, Dobyns WB, Qasrawi B, Winter RM, Innes AM, Voit T, Ross ME, Michaud JL, Déscarie JC, Barkovich AJ, Walsh CA. G protein-coupled receptor-dependent development of human frontal cortex. Science. 2004 Mar 26; 303(5666):2033-6. View abstract
  55. Xianhua Piao, Randall Collura, Alice S. Bailey, David Reich, Maryellen Ruvolo, and Christopher A. Walsh. Evolutionarily dynamic G-protein-coupled receptor regulates the development of human cerebral cortex. The American Society of Human Genetics 2004 Annual Meeting. 2004. View abstract
  56. Chang BS, Piao X, Bodell A, Basel-Vanagaite L, Straussberg R, Dobyns WB, Qasrawi B, Winter RM, Innes AM, Voit T, Grant PE, Barkovich AJ, Walsh CA. Bilateral frontoparietal polymicrogyria: clinical and radiological features in 10 families with linkage to chromosome 16. Ann Neurol. 2003 May; 53(5):596-606. View abstract
  57. Piao X, Basel-Vanagaite L, Straussberg R, Grant PE, Pugh EW, Doheny K, Doan B, Hong SE, Shugart YY, Walsh CA. An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to chromosome 16q12.2-21. Am J Hum Genet. 2002 Apr; 70(4):1028-33. View abstract
  58. Bennett DC, Trayner ID, Piao X, Easty DJ, Klüppel M, Alexander WS, Wagner EF, Bernstein A. recessive spotting: a linked locus that interacts with W/Kit but is not allelic. Genes Cells. 1998 Apr; 3(4):235-44. View abstract
  59. Piao X, Paulson R, van der Geer P, Pawson T, Bernstein A. Oncogenic mutation in the Kit receptor tyrosine kinase alters substrate specificity and induces degradation of the protein tyrosine phosphatase SHP-1. Proc Natl Acad Sci U S A. 1996 Dec 10; 93(25):14665-9. View abstract
  60. Piao X, Bernstein A. A point mutation in the catalytic domain of c-kit induces growth factor independence, tumorigenicity, and differentiation of mast cells. Blood. 1996 Apr 15; 87(8):3117-23. View abstract
  61. Xianhua Piao. Ph.D. Dissertation: Oncogenic Property of the Kit Receptor and Its Activating Mutant Allele. 1996. View abstract
  62. Xu WM, Piao XH, Addy L, Jamal M, Minden MD, Messner HA. Minimal residual disease in bone marrow transplant recipients with chronic myeloid leukemia. Bone Marrow Transplant. 1994 Aug; 14(2):299-306. View abstract
  63. Piao X, Curtis JE, Minkin S, Minden MD, Bernstein A. Expression of the Kit and KitA receptor isoforms in human acute myelogenous leukemia. Blood. 1994 Jan 15; 83(2):476-81. View abstract
  64. Bai Y, Piao XH, Luo QL, Mao BZ. Monoclonal antibody 55 (CD10) and complement used for purging autologous bone marrow in common acute lymphoblastic leukemia. Chin Med J (Engl). 1990 May; 103(5):385-90. View abstract
  65. Bai Y, Lu S, and Piao XH. Killing of Acute Lymphoblastic Leukemic Cells with Cytotoxic Monoclonal Antibody CD7. Chinese Journal of Hematology. 1990; 11:519-524. View abstract
  66. Mao BZ, Luo QL, Bai Y, Piao XH, and Zhang ZH. In Vitro Autologous Bone Marrow Purging and Phase I Clinical Trial. Journal of Clinical Medicine. 1989; 14:434-439. View abstract
  67. Piao XH and Bai Y. Separation, Purging, and Preservation of Bone Marrow Cells in Autologous Bone Marrow Transplantation. Journal of Clinical Hematology. 1988; 1(1):22-29. View abstract
  68. Piao XH, Liu Y, Bai Y. Elimination of Leukemic Cells from Bone Marrow with Monoclonal Antibody. Chinese Journal of Hematology. 1988; 9:331-333. View abstract
  69. Xianhua Piao. M.Sc. Thesis: In Vitro Purging and Autologous Bone Marrow Transplantation in Common Acute Lymphoblastic Leukemia Patients. 1987. View abstract