Skip to Content

Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 
Chin  Chiang

Chin Chiang, Ph.D.

Professor of Cell and Developmental Biology
Researcher

Contact Information:

Vanderbilt University Medical Center
4110-A Medical Center North
Nashville, TN 37232-8240
615-322-9422

Research Description

Our research focuses on the role Sonic hedgehog signaling plays in the pathogenesis of the two most common types of pediatric cancers, soft tissue sarcomas and brain tumors. We study the tumor cells-of-origin, initiation and propagation. In addition, we are also interested in identifying tumor biomarkers and compounds that inhibit their growth. We use state of the art approaches that include stem cell manipulation, molecular genetics, orthotopic grafting, proteomics, genome-wide RNA sequencing and CHIP.

Another area of interest is to understand how the complex brain circuitry is established from a rather small number of neural stem cells. We study signaling pathways that regulate brain stem cell proliferation and differentiation.

Publications
  • Bebesh, A.E., Fleming, J.T., Chiang, C., Carter, B.D. and Tyska, M.J.. Expression and localization of myosin-1d in the developing nervous system. Brain Res. 2012; 1440: 9.
  • Cheng, F.Y., Huang, X., Sarangi, A., Ketova, T., Cooper, M.K., Litingtung, Y. and Chiang, C.. Widespread contribution of Gdf7 lineage to cerebellar cell types and implications for Hedgehog-driven medulloblastoma formation. Plos One. 2012; 7: 35541.
  • Huang, X., Dubuc, A.M., Hashizume, R., Berg, J., He, Y., Chiang, C. Cooper, M.K., Northcott, P.A., Yatlor, M.D., Barnes, M.J., Tijan, T., Chen, J., Hackett, C.S., Weiss, W.A., David James, C., Rowitch, D.H., Shuman, M.A., Jan, Y.H. and Jan L.Y.. Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics. Genes Dev. 2012; 26: 1780.
  • Ryan K.E. and Chiang, C.. Hedgehog Secretion and Signal Transduction in Vertebrates. J. Biol. Chem. 2012; 287: 179015.
  • Mason, T.A., Kolobova, E., Liu, J., Roland, J.T., Chiang, C.. Darinaparsin is a multivalent chemotherapeutic which induces incomplete stress response with disruption of microtubules and Shh signaling. Plos One. 2011; 6((11)): 27699.
  • Huang X, Liu J, Ketova T, Fleming JT, Grover VK, Cooper MK, Litingtung Y, Chiang C. Transventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 May 5/4/2010; 107(18): 8422-7. PMID: 20400693, PMCID: PMC2889567, PII: 0911838107, DOI: 10.1073/pnas.0911838107, ISSN: 1091-6490.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20400693.
  • Huang, X., Ketova, T., Litingtung, Y. and Chiang, C. Isolation, Enrichment and Maintenance of Medulloblastoma Stem Cells. J. Vis. Exp. 2010; 43: 2086.
  • Huang, X., Sarangi, A., Ketova, T., Cooper, M. K., Litingtung, Y. and Chiang, C.. Intracranial Orthotopic Allografting of Medulloblastoma. J. Vis. Exp. 2010; 44: 2153.
  • Huang X, Ketova T, Fleming JT, Wang H, Dey SK, Litingtung Y, Chiang C. Sonic hedgehog signaling regulates a novel epithelial progenitor domain of the hindbrain choroid plexus. Development [print-electronic]. 2009 Aug; 136(15): 2535-43. PMID: 19570847, PMCID: PMC2709062, PII: dev.033795, DOI: 10.1242/dev.033795, ISSN: 0950-1991.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/19570847.
  • Oh S, Huang X, Liu J, Litingtung Y, Chiang C. Shh and Gli3 activities are required for timely generation of motor neuron progenitors. Dev. Biol [print-electronic]. 2009 Jul 7/15/2009; 331(2): 261-9. PMID: 19433083, PMCID: PMC2703695, PII: S0012-1606(09)00563-6, DOI: 10.1016/j.ydbio.2009.05.539, ISSN: 1095-564X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/19433083.
  • Li Y, Gordon J, Manley NR, Litingtung Y, Chiang C. Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis. Dev. Biol [print-electronic]. 2008 Oct 10/1/2008; 322(1): 145-55. PMID: 18692041, PMCID: PMC3780977, PII: S0012-1606(08)01081-6, DOI: 10.1016/j.ydbio.2008.07.021, ISSN: 1095-564X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18692041.
  • Huang X, Goudy SL, Ketova T, Litingtung Y, Chiang C. Gli3-deficient mice exhibit cleft palate associated with abnormal tongue development. Dev. Dyn. 2008 Oct; 237(10): 3079-87. PMID: 18816854, DOI: 10.1002/dvdy.21714, ISSN: 1058-8388.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18816854.
  • Fogel JL, Chiang C, Huang X, Agarwala S. Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling. Dev. Dyn. 2008 May; 237(5): 1359-72. PMID: 18429041, PMCID: PMC2586936, DOI: 10.1002/dvdy.21536, ISSN: 1058-8388.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18429041.
  • Zhang H, Lawson WE, Polosukhin VV, Pozzi A, Blackwell TS, Litingtung Y, Chiang C. Inhibitor of differentiation 1 promotes endothelial survival in a bleomycin model of lung injury in mice. Am. J. Pathol [print-electronic]. 2007 Oct; 171(4): 1113-26. PMID: 17717145, PMCID: PMC1988863, PII: S0002-9440(10)62377-2, DOI: 10.2353/ajpath.2007.070226, ISSN: 0002-9440.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17717145.
  • Huang X, Litingtung Y, Chiang C. Ectopic sonic hedgehog signaling impairs telencephalic dorsal midline development: implication for human holoprosencephaly. Hum. Mol. Genet [print-electronic]. 2007 Jun 6/15/2007; 16(12): 1454-68. PMID: 17468181, PII: ddm096, DOI: 10.1093/hmg/ddm096, ISSN: 0964-6906.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17468181.
  • Huang X, Litingtung Y, Chiang C. Region-specific requirement for cholesterol modification of sonic hedgehog in patterning the telencephalon and spinal cord. Development. 2007 Jun; 134(11): 2095-105. PMID: 17507410, PII: 134/11/2095, DOI: 10.1242/dev.000729, ISSN: 0950-1991.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17507410.
  • Li Y, Litingtung Y, Ten Dijke P, Chiang C. Aberrant Bmp signaling and notochord delamination in the pathogenesis of esophageal atresia. Dev. Dyn. 2007 Mar; 236(3): 746-54. PMID: 17260385, DOI: 10.1002/dvdy.21075, ISSN: 1058-8388.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17260385.
  • Guerrero, I and Chiang, C.. A conserved mechanism of Hedgehog gradient formation by lipid modifications. Trends in Cell Biology. 2007; 17: 1-5.
    Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed.
  • Li Y, Zhang H, Litingtung Y, Chiang C. Cholesterol modification restricts the spread of Shh gradient in the limb bud. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2006 Apr 4/25/2006; 103(17): 6548-53. PMID: 16611729, PMCID: PMC1458921, PII: 0600124103, DOI: 10.1073/pnas.0600124103, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16611729.
  • Chiang, C. From Oligodactyly to Polydactyly:role of Shh and Gli3 in limb morphogenesis. In Hedgehog-Gli Signaling and Human Disease, Edited by A. Ruiz I Altaba. 2006; 137-45.
  • Zhang, H., Litingtung, Y. and Chiang, C.. Sonic Hedgehog signaling in viceral organ development. In Shh and Gli signaling in Development. Edited by S. Howie and C. Fisher. 2006.
  • Oh S, Huang X, Chiang C. Specific requirements of sonic hedgehog signaling during oligodendrocyte development. Dev. Dyn. 2005 Nov; 234(3): 489-96. PMID: 15880651, DOI: 10.1002/dvdy.20422, ISSN: 1058-8388.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15880651.
  • van Bokhoven H, Celli J, van Reeuwijk J, Rinne T, Glaudemans B, van Beusekom E, Rieu P, Newbury-Ecob RA, Chiang C, Brunner HG. MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome. Nat. Genet [print-electronic]. 2005 May; 37(5): 465-7. PMID: 15821734, PII: ng1546, DOI: 10.1038/ng1546, ISSN: 1061-4036.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15821734.
  • Li Y, Zhang H, Choi SC, Litingtung Y, Chiang C. Sonic hedgehog signaling regulates Gli3 processing, mesenchymal proliferation, and differentiation during mouse lung organogenesis. Dev. Biol. 2004 Jun 6/1/2004; 270(1): 214-31. PMID: 15136151, PII: S0012160604001691, DOI: 10.1016/j.ydbio.2004.03.009, ISSN: 0012-1606.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15136151.
  • Powles N, Marshall H, Economou A, Chiang C, Murakami A, Dickson C, Krumlauf R, Maconochie M. Regulatory analysis of the mouse Fgf3 gene: control of embryonic expression patterns and dependence upon sonic hedgehog (Shh) signalling. Dev. Dyn. 2004 May; 230(1): 44-56. PMID: 15108308, DOI: 10.1002/dvdy.20028, ISSN: 1058-8388.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15108308.
  • Chiang CW, Kanies C, Kim KW, Fang WB, Parkhurst C, Xie M, Henry T, Yang E. Protein phosphatase 2A dephosphorylation of phosphoserine 112 plays the gatekeeper role for BAD-mediated apoptosis. Mol. Cell. Biol. 2003 Sep; 23(18): 6350-62. PMID: 12944463, PMCID: PMC193703, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12944463.
  • Litingtung Y, Dahn RD, Li Y, Fallon JF, Chiang C. Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity. Nature [print-electronic]. 2002 Aug 8/29/2002; 418(6901): 979-83. PMID: 12198547, PII: nature01033, DOI: 10.1038/nature01033, ISSN: 0028-0836.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12198547.
  • Liu W, Li G, Chien JS, Raft S, Zhang H, Chiang C, Frenz DA. Sonic hedgehog regulates otic capsule chondrogenesis and inner ear development in the mouse embryo. Dev. Biol. 2002 Aug 8/15/2002; 248(2): 240-50. PMID: 12167401, PII: S0012160602907335, ISSN: 0012-1606.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12167401.
  • Perriton CL, Powles N, Chiang C, Maconochie MK, Cohn MJ. Sonic hedgehog signaling from the urethral epithelium controls external genital development. Dev. Biol. 2002 Jul 7/1/2002; 247(1): 26-46. PMID: 12074550, PII: S0012160602906688, DOI: 10.1006/dbio.2002.0668, ISSN: 0012-1606.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12074550.
  • Ohkubo Y, Chiang C, Rubenstein JL. Coordinate regulation and synergistic actions of BMP4, SHH and FGF8 in the rostral prosencephalon regulate morphogenesis of the telencephalic and optic vesicles. Neuroscience. 2002; 111(1): 1-17. PMID: 11955708, PII: S0306452201006169, ISSN: 0306-4522.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11955708.
  • Chiang C, Litingtung Y, Harris MP, Simandl BK, Li Y, Beachy PA, Fallon JF. Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function. Dev. Biol. 2001 Aug 8/15/2001; 236(2): 421-35. PMID: 11476582, PII: S0012-1606(01)90346-X, DOI: 10.1006/dbio.2001.0346, ISSN: 0012-1606.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11476582.
  • Mo R, Kim JH, Zhang J, Chiang C, Hui CC, Kim PC. Anorectal malformations caused by defects in sonic hedgehog signaling. Am. J. Pathol. 2001 Aug; 159(2): 765-74. PMID: 11485934, PMCID: PMC1850556, PII: S0002-9440(10)61747-6, DOI: 10.1016/S0002-9440(10)61747-6, ISSN: 0002-9440.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11485934.
  • Chattopadhyay A, Chiang CW, Yang E. BAD/BCL-[X(L)] heterodimerization leads to bypass of G0/G1 arrest. Oncogene. 2001 Jul 7/27/2001; 20(33): 4507-18. PMID: 11494146, DOI: 10.1038/sj.onc.1204584, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11494146.
  • Chiang CW, Harris G, Ellig C, Masters SC, Subramanian R, Shenolikar S, Wadzinski BE, Yang E. Protein phosphatase 2A activates the proapoptotic function of BAD in interleukin- 3-dependent lymphoid cells by a mechanism requiring 14-3-3 dissociation. Blood. 2001 Mar 3/1/2001; 97(5): 1289-97. PMID: 11222372, ISSN: 0006-4971.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11222372.
  • Pak JH, Huang FL, Li J, Balschun D, Reymann KG, Chiang C, Westphal H, Huang KP. Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: a study with knockout mice. Proc. Natl. Acad. Sci. U.S.A. 2000 Oct 10/10/2000; 97(21): 11232-7. PMID: 11016969, PMCID: PMC17183, PII: 210184697, DOI: 10.1073/pnas.210184697, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11016969.
  • Litingtung Y, Chiang C. Control of Shh activity and signaling in the neural tube. Dev. Dyn. 2000 Oct; 219(2): 143-54. PMID: 11002335, PII: 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1050>3.0.CO;2-Q, DOI: 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1050>3.0.CO;2-Q, ISSN: 1058-8388.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11002335.
  • Litingtung Y, Chiang C. Specification of ventral neuron types is mediated by an antagonistic interaction between Shh and Gli3. Nat. Neurosci. 2000 Oct; 3(10): 979-85. PMID: 11017169, DOI: 10.1038/79916, ISSN: 1097-6256.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11017169.
  • Borycki AG, Brunk B, Tajbakhsh S, Buckingham M, Chiang C, Emerson CP. Sonic hedgehog controls epaxial muscle determination through Myf5 activation. Development. 1999 Sep; 126(18): 4053-63. PMID: 10457014, ISSN: 0950-1991.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10457014.
  • Pierani A, Brenner-Morton S, Chiang C, Jessell TM. A sonic hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord. Cell. 1999 Jun 6/25/1999; 97(7): 903-15. PMID: 10399918, PII: S0092-8674(00)80802-8, ISSN: 0092-8674.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10399918.
  • Chiang C, Swan RZ, Grachtchouk M, Bolinger M, Litingtung Y, Robertson EK, Cooper MK, Gaffield W, Westphal H, Beachy PA, Dlugosz AA. Essential role for Sonic hedgehog during hair follicle morphogenesis. Dev. Biol. 1999 Jan 1/1/1999; 205(1): 1-9. PMID: 9882493, PII: S0012-1606(98)99103-5, DOI: 10.1006/dbio.1998.9103, ISSN: 0012-1606.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9882493.
  • Litingtung Y, Lei L, Westphal H, Chiang C. Sonic hedgehog is essential to foregut development. Nat. Genet. 1998 Sep; 20(1): 58-61. PMID: 9731532, DOI: 10.1038/1717, ISSN: 1061-4036.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9731532.
  • Kos L, Chiang C, Mahon KA. Mediolateral patterning of somites: multiple axial signals, including Sonic hedgehog, regulate Nkx-3.1 expression. Mech. Dev. 1998 Jan; 70(1-2): 25-34. PMID: 9510022, ISSN: 0925-4773.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9510022.
  • Knezevic, V., De Santo, R., Schughart, K., Huffstadt, U., Chiang, C., Mahon, K.A. and Mackem, S. Hoxd-12 differentially affects preaxial and postaxial chondrogenic branches in the limb and regulates sonic hedgehog in a positive feedback loop. Development. 1997; 124: 4523-36.
  • Yuryev A, Patturajan M, Litingtung Y, Joshi RV, Gentile C, Gebara M, Corden JL. The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins. Proc. Natl. Acad. Sci. U.S.A. 1996 Jul 7/9/1996; 93(14): 6975-80. PMID: 8692929, PMCID: PMC38919, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8692929.
  • Chiang C, Litingtung Y, Lee E, Young K, Corden JL, Westphal H and Beachy PA. Cyclopia and defective axial patterning in mice lacking Sonic Hedgehog gene function. Nature. 1996; 383: 407-13.
  • Chiang, C., Yong, K.E., and Beachy, P.A.. Controlof drosphila trachael branching by the novel homeodomain gene unplugges, a regulatory target for genes of the bithorax complex. Development. 1995; 121: 3901-12.
  • Fan, C.-M., Porter, J.A., Chiang, C., Chang, D.T., Beachy, P.A., Tessier,-Lavigne, M.. Long range sclerotome induction by Sonic Hedgehog: direct role of the amino-terminal clleavage product and modulation by the cyclic AMP signalling pathway. Cell. 1995; 81: 457-65.
  • Hynes, M., Porter, J.A., Chiang, C, Chang, D., Tessier-Lavigne, M., Beachy P.A., and Rosenthal, A.. Induction of midbrain dopaminergic neurons product of hedgehog autoproteolysis. Neuron. 1995; 15: 35-44.
  • Lopez, A., Chang, D.T., Chiang, C., Porter, J., maria, A.R., Simandl, K., Beachy, P.A., and Fallon, J.F.. Limb patterning activity and restricted posterior localization of the amino terminal product of hedgehog autoproteolysis. Current Biology. 1995; 5: 791-6.
  • Roelink, H., Porter, J., Chiang, C., Tanabe, Y., Chang, D.T., Beachy, P.A., and Jessell, T.M.. Concentration-dependent induction of floor plate and motor neuron differentiation by the amino terminal autoproteolytic fragment of Sonic Hedgehog. Cell. 1995; 81: 445-55.
  • Chang, D.T., Lopez, A., von Kessler, D.P., Chiang, C., Simandl, K., Renbin, Z., Seldin, M.F., Fallon, J.F., and Beachy, P.A. Products, genetic linkage, and limb patterning activity of a murine hedgehog gene. Development. 1994; 120: 3339-53.
  • Chiang, C., andBeachy, P.A. Expression of a novel Toll-like gene spans the parasegment boundary and contributes to hedgehog function in the adult eye of Drosophila. Mech. Dev. 1994; 47: 225-39.
  • Chiang, C.,, Patel, N., Young, K., and Beachy, P.A.. The novel homeodomain gene buttonless specifies differentiation and axonal guidance functions of Drosophila dorsal median cells. Development. 1994; 120: 3581-93.