Chin Chiang, M.D., Ph.D.

Professor

chin.chiang@vanderbilt.edu

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Faculty Appointments
Professor of Cell and Developmental Biology
Education
Ph.D., Genetics and Cell biology, Washington State University, Pullman, WashingtonM.D., Chemical engineering, Washington State University, Pullman, WashingtonB.S., Chemical engineering, State University of New York, Buffalo, New York
Office Address
4114, MRB3
Nashville, TN 37232-8240
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.
Research Keywords
Hedgehog signaling in development and cancer
Publications
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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Guerrero, I and Chiang, C.. A conserved mechanism of Hedgehog gradient formation by lipid modifications. Trends in Cell Biology. 2007; 17: 1-5.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.,, 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.

Available Postdoctoral Position Details
Posted: 8/23/2013
Contact Chin Chiang at chin.chiang@vanderbilt.edu for more details.