Xianhua Piao, MD, PhD
Professor
Pediatrics
School of Medicine

Working in neonatal intensive care unit and laboratory, Dr. Piao’s career follows the bedside-to-bench-to-bedside paradigm. Her research began by characterizing an autosomal recessive human brain malformation that she and her mentor Chris Walsh termed bilateral frontoparietal polymicrogyria (BFPP). Together, they discovered that germline loss-of-function mutations in the adhesion G-protein-coupled receptor (aGPCR) GPR56, also called ADGRG1, cause BFPP. Over time, this discovery transformed our understanding of polymicrogyria and yielded a molecular diagnostic. Following the thread of GPR56 biology also led to a vigorous bench research program. Dr. Piao’s research team has steadily uncovered a remarkable diversity of cell type- and ligand-specific functions of GPR56 during various stages of brain development and homeostasis, including cortical patterning, central nervous system myelin formation and repair, and synaptic refinement. In doing so, Dr. Piao undertook a pioneering role in deorphanizing aGPCRs and revealing mechanisms underlying aGPCR-mediated cell-cell and cell-matrix interactions. This basic science also provides foundational knowledge for drug discoveries in targeting aGPCRs, the second largest human GPCR family. In January 2019, Dr. Piao was recruited from Harvard Medical School / Boston Children's Hospital to UCSF to direct the Newborn Brain Research Institute and assume the Benioff Professorship in Children’s Health. In her new role, Dr. Piao has built a collaborative and cohesive team that broadly addresses how early insults, such as maternal inflammation and hypoxic-ischemic injuries affect fetal and neonatal brain development.

• Microglial GPR56 is the molecular target of maternal immune activation-induced parvalbumin-positive interneuron deficits.
  Science advances 2022 Yu D, Li T, Delpech JC, Zhu B, Kishore P, Koshi T, Luo R, Pratt KJB, Popova G, Nowakowski TJ, Villeda SA, Piao X
• The Inhibitory Receptor GPR56 (Adgrg1) Is Specifically Expressed by Tissue-Resident Memory T Cells in Mice But Dispensable for Their Differentiation and Function In Vivo.
  Cells 2021 Hsiao CC, Kragten NAM, Piao X, Hamann J, van Gisbergen KPJM
• Phospholipid-flippase chaperone CDC50A is required for synapse maintenance by regulating phosphatidylserine exposure.
  The EMBO journal 2021 Li T, Yu D, Oak HC, Zhu B, Wang L, Jiang X, Molday RS, Kriegstein A, Piao X
• Human microglia states are conserved across experimental models and regulate neural stem cell responses in chimeric organoids.
  Cell stem cell 2021 Popova G, Soliman SS, Kim CN, Keefe MG, Hennick KM, Jain S, Li T, Tejera D, Shin D, Chhun BB, McGinnis CS, Speir M, Gartner ZJ, Mehta SB, Haeussler M, Hengen KB, Ransohoff RR, Piao X, Nowakowski TJ
• The association of COVID-19 infection in pregnancy with preterm birth: A retrospective cohort study in California.
  Lancet regional health. Americas 2021 Karasek D, Baer RJ, McLemore MR, Bell AJ, Blebu BE, Casey JA, Coleman-Phox K, Costello JM, Felder JN, Flowers E, Fuchs JD, Gomez AM, Karvonen K, Kuppermann M, Liang L, McKenzie-Sampson S, McCulloch CE…
• Association of Maternal Immune Activation during Pregnancy and Neurologic Outcomes in Offspring.
  The Journal of pediatrics 2021 Jain S, Baer RJ, McCulloch CE, Rogers E, Rand L, Jelliffe-Pawlowski L, Piao X
• Unexpected redundancy of Gpr56 and Gpr97 during hematopoietic cell development and differentiation.
  Blood advances 2021 Maglitto A, Mariani SA, de Pater E, Rodriguez-Seoane C, Vink CS, Piao X, Lukke ML, Dzierzak E
• GPR56/ADGRG1 is a platelet collagen-responsive GPCR and hemostatic sensor of shear force.
  Proceedings of the National Academy of Sciences of the United States of America 2020 Yeung J, Adili R, Stringham EN, Luo R, Vizurraga A, Rosselli-Murai LK, Stoveken HM, Yu M, Piao X, Holinstat M, Tall GG
• Cell type-specific evaluation of ADGRG1/GPR56 function in developmental central nervous system myelination.
  Glia 2020 Chiou B, Gao C, Giera S, Folts CJ, Kishore P, Yu D, Oak HC, Jiang R, Piao X
• A splicing isoform of GPR56 mediates microglial synaptic refinement via phosphatidylserine binding.
  The EMBO journal 2020 Li T, Chiou B, Gilman CK, Luo R, Koshi T, Yu D, Oak HC, Giera S, Johnson-Venkatesh E, Muthukumar AK, Stevens B, Umemori H, 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.
  The Journal of biological chemistry 2019 Zhu B, Luo R, Jin P, Li T, Oak HC, Giera S, Monk KR, Lak P, Shoichet BK, Piao X
• The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors.
  Annals of the New York Academy of Sciences 2019 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, …
• Long noncoding RNAs interact with mRNAs: A new perspective on the mechanism of premature brain injury.
  Neuroscience letters 2019 Chen R, Piao X, Xiao M, Wang F, Liu L
• Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556.
  Neurogenetics 2019 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
• Adhesion G Protein-Coupled Receptors as Drug Targets for Neurological Diseases.
  Trends in pharmacological sciences 2019 Folts CJ, Giera S, Li T, Piao X
• Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes.
  Immunity 2018 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, …
• The adhesion receptor GPR56 is activated by extracellular matrix collagen III to improve β-cell function.
  Cellular and molecular life sciences : CMLS 2018 Olaniru OE, Pingitore A, Giera S, Piao X, Castañera González R, Jones PM, Persaud SJ
• Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells.
  eLife 2018 Giera S, Luo R, Ying Y, Ackerman SD, Jeong SJ, Stoveken HM, Folts CJ, Welsh CA, Tall GG, Stevens B, Monk KR, Piao X
• GPR56/ADGRG1 regulates development and maintenance of peripheral myelin.
  The Journal of experimental medicine 2018 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 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma.
  Cell reports 2017 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, …
• Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy.
  Muscle & nerve 2017 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
• Adhesion G-protein coupled receptors and extracellular matrix proteins: Roles in myelination and glial cell development.
  Developmental dynamics : an official publication of the American Association of Anatomists 2017 Mehta P, Piao X
• Gpr126/Adgrg6 Has Schwann Cell Autonomous and Nonautonomous Functions in Peripheral Nerve Injury and Repair.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2016 Mogha A, Harty BL, Carlin D, Joseph J, Sanchez NE, Suter U, Piao X, Cavalli V, Monk KR
• Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains.
  Neuron 2016 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
• Adhesion G protein-coupled receptors in nervous system development and disease.
  Nature reviews. Neuroscience 2016 Langenhan T, Piao X, Monk KR
• Adhesion GPCRs as Novel Actors in Neural and Glial Cell Functions: From Synaptogenesis to Myelination.
  Handbook of experimental pharmacology 2016 Sigoillot SM, Monk KR, Piao X, Selimi F, Harty BL
• Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury.
  Acta neuropathologica 2015 Chen P, Piao X, Bonaldo P
• Tethered agonists: a new mechanism underlying adhesion G protein-coupled receptor activation.
  Journal of receptor and signal transduction research 2015 Schöneberg T, Liebscher I, Luo R, Monk KR, Piao X
• High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice.
  Stem cell research 2015 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
• The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211.
  Neuron 2015 Petersen SC, Luo R, Liebscher I, Giera S, Jeong SJ, Mogha A, Ghidinelli M, Feltri ML, Schöneberg T, Piao X, Monk KR
• The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development.
  Nature communications 2015 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 GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA.
  Nature communications 2015 Ackerman SD, Garcia C, Piao X, Gutmann DH, Monk KR
• International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.
  Pharmacological reviews 2015 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, …
• New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors.
  Annals of the New York Academy of Sciences 2014 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, …
• G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.
  Proceedings of the National Academy of Sciences of the United States of America 2014 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
• Mechanism for adhesion G protein-coupled receptor GPR56-mediated RhoA activation induced by collagen III stimulation.
  PloS one 2014 Luo R, Jeong SJ, Yang A, Wen M, Saslowsky DE, Lencer WI, Araç D, Piao X
• Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning.
  Science (New York, N.Y.) 2014 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 …
• 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.
  The FEBS journal 2013 Wu MP, Doyle JR, Barry B, Beauvais A, Rozkalne A, Piao X, Lawlor MW, Kopin AS, Walsh CA, Gussoni E
• GPR56 functions together with α3β1 integrin in regulating cerebral cortical development.
  PloS one 2013 Jeong SJ, Luo R, Singer K, Giera S, Kreidberg J, Kiyozumi D, Shimono C, Sekiguchi K, Piao X
• Dissecting signaling and functions of adhesion G protein-coupled receptors.
  Annals of the New York Academy of Sciences 2012 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…
• GPR56 and the developing cerebral cortex: cells, matrix, and neuronal migration.
  Molecular neurobiology 2012 Singer K, Luo R, Jeong SJ, Piao X
• Characterization of G protein-coupled receptor 56 protein expression in the mouse developing neocortex.
  The Journal of comparative neurology 2012 Jeong SJ, Luo R, Li S, Strokes N, Piao X
• Disease-associated mutations prevent GPR56-collagen III interaction.
  PloS one 2012 Luo R, Jin Z, Deng Y, Strokes N, Piao X
• Loss of Col3a1, the gene for Ehlers-Danlos syndrome type IV, results in neocortical dyslamination.
  PloS one 2012 Jeong SJ, Li S, Luo R, Strokes N, Piao X
• G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination.
  Proceedings of the National Academy of Sciences of the United States of America 2011 Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X
• A novel GPR56 mutation causes bilateral frontoparietal polymicrogyria.
  Pediatric neurology 2011 Luo R, Yang HM, Jin Z, Halley DJ, Chang BS, MacPherson L, Brueton L, Piao X
• G protein-coupled receptor56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination
  Proc Natl Acad Sci USA, 108(31), 12925-30. 2011 Luo, R., Jeong, S.J., Jin, Z., Strokes, N., Li, S., Piao, X.
• Adhesion-GPCRs in the CNS.
  Advances in experimental medicine and biology 2010 Strokes N, Piao X
• GPR56 and its related diseases.
  Progress in molecular biology and translational science 2009 Jin Z, Luo R, Piao X
• GPR56-regulated granule cell adhesion is essential for rostral cerebellar development.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2009 Koirala S, Jin Z, Piao X, Corfas G
• GPR56 regulates pial basement membrane integrity and cortical lamination.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2008 Li S, Jin Z, Koirala S, Bu L, Xu L, Hynes RO, Walsh CA, Corfas G, Piao X
• Disease-associated mutations affect GPR56 protein trafficking and cell surface expression.
  Human molecular genetics 2007 Jin Z, Tietjen I, Bu L, Liu-Yesucevitz L, Gaur SK, Walsh CA, Piao X
• Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes.
  Annals of neurology 2005 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
• A novel signaling mechanism in brain development.
  Pediatric research 2004 Piao X, Walsh CA
• G protein-coupled receptor-dependent development of human frontal cortex.
  Science (New York, N.Y.) 2004 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 Piao, X., Hill, R.S., Bodell, A., Chang, B.S., Basel-Vanagaite, L., Straussberg, R., Dobyns, W.B., Qasrawi, B., Winter, R.M., Innes, A.M., Voit, T., Ross, M.E., Michaud, J.L., Déscarie, J.C., …
• Bilateral frontoparietal polymicrogyria: clinical and radiological features in 10 families with linkage to chromosome 16.
  Annals of neurology 2003 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
• An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to chromosome 16q12.2-21.
  American journal of human genetics 2002 Piao X, Basel-Vanagaite L, Straussberg R, Grant PE, Pugh EW, Doheny K, Doan B, Hong SE, Shugart YY, Walsh CA
• recessive spotting: a linked locus that interacts with W/Kit but is not allelic.
  Genes to cells : devoted to molecular & cellular mechanisms 1998 Bennett DC, Trayner ID, Piao X, Easty DJ, Klüppel M, Alexander WS, Wagner EF, Bernstein A
• Oncogenic mutation in the Kit receptor tyrosine kinase alters substrate specificity and induces degradation of the protein tyrosine phosphatase SHP-1.
  Proceedings of the National Academy of Sciences of the United States of America 1996 Piao X, Paulson R, van der Geer P, Pawson T, Bernstein A
• A point mutation in the catalytic domain of c-kit induces growth factor independence, tumorigenicity, and differentiation of mast cells.
  Blood 1996 Piao X, Bernstein A
• Minimal residual disease in bone marrow transplant recipients with chronic myeloid leukemia.
  Bone marrow transplantation 1994 Xu WM, Piao XH, Addy L, Jamal M, Minden MD, Messner HA
• Expression of the Kit and KitA receptor isoforms in human acute myelogenous leukemia.
  Blood 1994 Piao X, Curtis JE, Minkin S, Minden MD, Bernstein A
• The preliminary observation on immunosuppressive effect of norcantharidin in mice.
  Immunopharmacology and immunotoxicology 1993 Yan MS, Xiue S, Wei LX, Piao XH
• Monoclonal antibody 55 (CD10) and complement used for purging autologous bone marrow in common acute lymphoblastic leukemia.
  Chinese medical journal 1990 Bai Y, Piao XH, Luo QL, Mao BZ