Xianhua Piao, MD, PhD

Professor in Residence
[email protected]
+1 415 502-3460

During development, cells of the brain execute an astonishingly intricate choreographed process that culminates in the precise localization of neurons wired in functional networked circuitry. After the formation and wiring completed, various cells continue to dialogue to maintain normal brain function. Errors in such interactions contribute to neurodevelopmental conditions including autism, schizophrenia, and cerebral palsy as well as neurodegeneration, such as Alzheimer’s disease. However, the molecular mechanisms underlying these dynamic interactions remain largely unknown. The Piao Lab seeks to understand how cells in the brain communicate with each other and with the extracellular matrix (ECM) during development and brain homeostasis and how perturbation of the communications leads to neurological disorders. Our current ongoing projects are centered on:

  1. Central Nervous System (CNS) Myelination
  2. Neuro-immune interplays during interneuron development 
  3. The impact of maternal immune activation on brain development 
  4. Molecular mechanisms underlying microglia-mediated synaptic pruning 
  5. Glial-glial and glial-neuronal interactions in Alzheimer’s disease
Research Summary: 
Neuro-immune interplay in brain development and disease.

Websites

Publications: 

Microglia regulate GABAergic neurogenesis in prenatal human brain through IGF1.

bioRxiv : the preprint server for biology

Yu D, Jain S, Wangzhou A, De Florencio S, Zhu B, Kim JY, Choi JJ, Paredes MF, Nowakowski TJ, Huang EJ, Piao X

Adhesion G protein-coupled receptor ADGRG1 promotes protective microglial response in Alzheimer's disease.

bioRxiv : the preprint server for biology

Zhu B, Wangzhou A, Yu D, Li T, Schmidt R, De Florencio SL, Chao L, Perez Y, Grinberg LT, Spina S, Ransohoff RM, Kriegstein AR, Seeley WW, Nowakowski T, Piao X

Loss of cardiomyocyte-specific adhesion G-protein-coupled receptor G1 (ADGRG1/GPR56) promotes pressure overload-induced heart failure.

Bioscience reports

Einspahr J, Xu H, Roy R, Dietz N, Melchior J, Raja J, Carter R, Piao X, Tilley DG

Assessing for prenatal risk factors associated with infant neurologic morbidity using a multivariate analysis.

Journal of perinatology : official journal of the California Perinatal Association

Jain S, Oltman S, Rogers E, Ryckman K, Petersen M, Baer RJ, Rand L, Piao X, Jelliffe-Pawlowski L

A cross-species proteomic map reveals neoteny of human synapse development.

Nature

Wang L, Pang K, Zhou L, Cebrián-Silla A, González-Granero S, Wang S, Bi Q, White ML, Ho B, Li J, Li T, Perez Y, Huang EJ, Winkler EA, Paredes MF, Kovner R, Sestan N, Pollen AA, Liu P, Li J, Piao X, García-Verdugo JM, Alvarez-Buylla A, Liu Z, Kriegstein AR

Collagen VI Is a Gi-Biased Ligand of the Adhesion GPCR GPR126/ADGRG6.

Cells

Wilde C, Chaudhry PM, Luo R, Simon KU, Piao X, Liebscher I

GPR56 S4 variant is required for microglia-mediated synaptic pruning.

Glia

Li T, Luo R, Schmidt R, D'Alessandro N, Kishore P, Zhu B, Yu D, Piao X

Microglial GPR56 is the molecular target of maternal immune activation-induced parvalbumin-positive interneuron deficits.

Science advances

Yu D, Li T, Delpech JC, Zhu B, Kishore P, Koshi T, Luo R, Pratt KJB, Popova G, Nowakowski TJ, Villeda SA, Piao X

Phospholipid-flippase chaperone CDC50A is required for synapse maintenance by regulating phosphatidylserine exposure.

The EMBO journal

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

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

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, Oltman SP, Pantell MS, Piao X, Prather AA, Schmidt RJ, Scott KA, Spellen S, Stookey JD, Tesfalul M, Rand L, Jelliffe-Pawlowski LL

Association of Maternal Immune Activation during Pregnancy and Neurologic Outcomes in Offspring.

The Journal of pediatrics

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

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

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

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

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

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

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

Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556.

Neurogenetics

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

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

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

The adhesion receptor GPR56 is activated by extracellular matrix collagen III to improve β-cell function.

Cellular and molecular life sciences : CMLS

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

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

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

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

Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy.

Muscle & nerve

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

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

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

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

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

Sigoillot SM, Monk KR, Piao X, Selimi F, Harty BL

Tethered agonists: a new mechanism underlying adhesion G protein-coupled receptor activation.

Journal of receptor and signal transduction research

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

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

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

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

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

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

New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors.

Annals of the New York Academy of Sciences

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

G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

Proceedings of the National Academy of Sciences of the United States of America

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

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.)

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

GPR56 functions together with α3β1 integrin in regulating cerebral cortical development.

PloS one

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

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

GPR56 and the developing cerebral cortex: cells, matrix, and neuronal migration.

Molecular neurobiology

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

Jeong SJ, Luo R, Li S, Strokes N, Piao X

Disease-associated mutations prevent GPR56-collagen III interaction.

PloS one

Luo R, Jin Z, Deng Y, 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

Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X

A novel GPR56 mutation causes bilateral frontoparietal polymicrogyria.

Pediatric neurology

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.

Luo, R., Jeong, S.J., Jin, Z., Strokes, N., Li, S., Piao, X.

Adhesion-GPCRs in the CNS.

Advances in experimental medicine and biology

Strokes N, Piao X

GPR56 and its related diseases.

Progress in molecular biology and translational science

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

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

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

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

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

Piao X, Walsh CA

G protein-coupled receptor-dependent development of human frontal cortex.

Science (New York, N.Y.)

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

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., Barkovich, A.J., Walsh, C.

Bilateral frontoparietal polymicrogyria: clinical and radiological features in 10 families with linkage to chromosome 16.

Annals of neurology

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

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

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

Piao X, Paulson R, van der Geer P, Pawson T, Bernstein A

Minimal residual disease in bone marrow transplant recipients with chronic myeloid leukemia.

Bone marrow transplantation

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

Piao X, Curtis JE, Minkin S, Minden MD, Bernstein A

The preliminary observation on immunosuppressive effect of norcantharidin in mice.

Immunopharmacology and immunotoxicology

Yan MS, Xiue S, Wei LX, Piao XH