Katty Kang, M.D., Ph.D.

Katty Kang, M.D., Ph.D.

Associate Professor of Neurology

: jingqiong.kang@vanderbilt.edu
: (615) 936-8399
: 465 21st Ave. South
Nashville, Tennessee - 37232

Research Description

The Kang Laboratory is interested in understanding the role of GABAergic signaling in disease conditions as well as in normal brain development. Currently, lab staff members are investigating the molecular pathophysiology of genetic variations in GABAA receptor subunits and two common pediatric syndromes: epilepsy and autism. They are trying to understand why a single nucleotide change in a particular GABAA receptor subunit gene could give rise to severe epilepsy, impaired social and learning abilities as well as other comorbidities which could define the whole life of a child. They use in vitro approaches to understand the details of how a mutant GABAA receptor subunit gene and protein behaves and the adaptive responses of the host cell. They use in vivo approaches, such as genetically modified mouse models, to understand the changes at more physiological and systematic levels. Lab staffers aim to dissect out the detailed changes at gene, protein, cell, neural circuitry, and behavioral levels for given GABAA subunit gene mutations and how the changes give rise to clinic phenotypes. Their final goal is to identify mechanism-based therapies for those who suffer from these disorders in order to improve patients’ treatments and life outcomes.

Selected Publications

Huang X, Zhou C, Tian M, Kang JQ, Shen W, Verdier K, Pimenta A, MacDonald RL. Overexpressing wild-type ¿2 subunits rescued the seizure phenotype in Gabrg2(+/Q390X) Dravet syndrome mice. Epilepsia [print-electronic]. 2017 Aug; 58(8): 1451-61. PMID: 28586508, PMCID: PMC5554098, DOI: 10.1111/epi.13810, ISSN: 1528-1167.
Warner TA, Liu Z, Macdonald RL, Kang JQ. Heat induced temperature dysregulation and seizures in Dravet Syndrome/GEFS+ Gabrg2(+/Q390X) mice. Epilepsy Res [print-electronic]. 2017 Aug; 134: 1-8. PMID: 28505490, PMCID: PMC5512282, PII: S0920-1211(17)30262-0, DOI: 10.1016/j.eplepsyres.2017.04.020, ISSN: 1872-6844.
Ishii A, Kang JQ, Schornak CC, Hernandez CC, Shen W, Watkins JC, Macdonald RL, Hirose S. A de novo missense mutation of GABRB2 causes early myoclonic encephalopathy. J. Med. Genet [print-electronic]. 2017 Mar; 54(3): 202-11. PMID: 27789573, PMCID: PMC5384423, PII: jmedgenet-2016-104083, DOI: 10.1136/jmedgenet-2016-104083, ISSN: 1468-6244.
Delahanty RJ, Zhang Y, Bichell TJ, Shen W, Verdier K, Macdonald RL, Xu L, Boyd K, Williams J, Kang JQ. Beyond Epilepsy and Autism: Disruption of GABRB3 Causes Ocular Hypopigmentation. Cell Rep. 2016 Dec 12/20/2016; 17(12): 3115-24. PMID: 28009282, PMCID: PMC5240804, PII: S2211-1247(16)31641-2, DOI: 10.1016/j.celrep.2016.11.067, ISSN: 2211-1247.
Wang J, Shen D, Xia G, Shen W, Macdonald RL, Xu D, Kang JQ. Differential protein structural disturbances and suppression of assembly partners produced by nonsense GABRG2 epilepsy mutations: implications for disease phenotypic heterogeneity. Sci Rep. 2016 Oct 10/20/2016; 6: 35294. PMID: 27762395, PMCID: PMC5071880, PII: srep35294, DOI: 10.1038/srep35294, ISSN: 2045-2322.
Kang JQ, Macdonald RL. Molecular Pathogenic Basis for GABRG2 Mutations Associated With a Spectrum of Epilepsy Syndromes, From Generalized Absence Epilepsy to Dravet Syndrome. JAMA Neurol. 2016 Aug 8/1/2016; 73(8): 1009-16. PMID: 27367160, PMCID: PMC5426359, PII: 2529988, DOI: 10.1001/jamaneurol.2016.0449, ISSN: 2168-6157.
Warner TA, Shen W, Huang X, Liu Z, Macdonald RL, Kang JQ. Differential molecular and behavioural alterations in mouse models of GABRG2 haploinsufficiency versus dominant negative mutations associated with human epilepsy. Hum. Mol. Genet [print-electronic]. 2016 Aug 8/1/2016; 25(15): 3192-207. PMID: 27340224, PMCID: PMC5179921, PII: ddw168, DOI: 10.1093/hmg/ddw168, ISSN: 1460-2083.
Xia G, P Pourali S, Warner TA, Zhang CQ, L Macdonald R, Kang JQ. Altered GABAA receptor expression in brainstem nuclei and SUDEP in Gabrg2(+/Q390X) mice associated with epileptic encephalopathy. Epilepsy Res [print-electronic]. 2016 Jul; 123: 50-4. PMID: 27131289, PMCID: PMC5433248, PII: S0920-1211(16)30049-3, DOI: 10.1016/j.eplepsyres.2016.04.002, ISSN: 1872-6844.
Wang J, Luttrell J, Zhang N, Khan S, Shi N, Wang MX, Kang JQ, Wang Z, Xu D. Exploring Human Diseases and Biological Mechanisms by Protein Structure Prediction and Modeling. Adv. Exp. Med. Biol. 2016; 939: 39-61. PMID: 27807743, DOI: 10.1007/978-981-10-1503-8_3, ISSN: 0065-2598.
Kang JQ, Shen W, Zhou C, Xu D, Macdonald RL. The human epilepsy mutation GABRG2(Q390X) causes chronic subunit accumulation and neurodegeneration. Nat. Neurosci [print-electronic]. 2015 Jul; 18(7): 988-96. PMID: 26005849, PMCID: PMC4482801, PII: nn.4024, DOI: 10.1038/nn.4024, ISSN: 1546-1726.
Warner TA, Kang JQ, Kennard JA, Harrison FE. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer’s disease. Epilepsy Res [print-electronic]. 2015 Feb; 110: 20-5. PMID: 25616451, PMCID: PMC4306812, PII: S0920-1211(14)00333-7, DOI: 10.1016/j.eplepsyres.2014.11.017, ISSN: 1872-6844.
Kang JQ, Shen W, Macdonald RL. Trafficking-deficient mutant GABRG2 subunit amount may modify epilepsy phenotype. Ann. Neurol [print-electronic]. 2013 Oct; 74(4): 547-59. PMID: 23720301, PMCID: PMC3839255, DOI: 10.1002/ana.23947, ISSN: 1531-8249.
Shah CR, Forsberg CG, Kang JQ, Veenstra-VanderWeele J. Letting a typical mouse judge whether mouse social interactions are atypical. Autism Res [print-electronic]. 2013 Jun; 6(3): 212-20. PMID: 23436806, PMCID: PMC3664268, DOI: 10.1002/aur.1280, ISSN: 1939-3806.
Kang JQ, Barnes G. A common susceptibility factor of both autism and epilepsy: functional deficiency of GABA A receptors. J Autism Dev Disord. 2013 Jan; 43(1): 68-79. PMID: 22555366, DOI: 10.1007/s10803-012-1543-7, ISSN: 1573-3432.
Kang JQ, Shen W, Macdonald RL. Trafficking-deficient mutant GABRG2 subunit amount may modify epilepsy phenotype. 2013.
Macdonald RL, Kang JQ. MRNA surveillance and endoplasmic reticulum quality control processes alter biogenesis of mutant GABAA receptor subunits associated with genetic epilepsies. Epilepsia. 2012 Dec; 53 Suppl 9: 59-70. PMID: 23216579, PMCID: PMC3762703, DOI: 10.1111/epi.12035, ISSN: 1528-1167.
Macdonald RL, Kang JQ, Gallagher MJ. GABAA Receptor Subunit Mutations and Genetic Epilepsies. 2012.
Delahanty RJ, Kang JQ, Brune CW, Kistner EO, Courchesne E, Cox NJ, Cook EH, Macdonald RL, Sutcliffe JS. Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism. Mol. Psychiatry [print-electronic]. 2011 Jan; 16(1): 86-96. PMID: 19935738, PMCID: PMC3428055, PII: mp2009118, DOI: 10.1038/mp.2009.118, ISSN: 1476-5578.
Kang JQ, Shen W, Lee M, Gallagher MJ, Macdonald RL. Slow degradation and aggregation in vitro of mutant GABAA receptor gamma2(Q351X) subunits associated with epilepsy. J. Neurosci. 2010 Oct 10/13/2010; 30(41): 13895-905. PMID: 20943930, PMCID: PMC2976503, PII: 30/41/13895, DOI: 10.1523/JNEUROSCI.2320-10.2010, ISSN: 1529-2401.
Macdonald RL, Kang JQ, Gallagher MJ. Mutations in GABAA receptor subunits associated with genetic epilepsies. J. Physiol. (Lond.) [print-electronic]. 2010 Jun 6/1/2010; 588(Pt 11): 1861-9. PMID: 20308251, PMCID: PMC2901974, PII: jphysiol.2010.186999, DOI: 10.1113/jphysiol.2010.186999, ISSN: 1469-7793.
Kang JQ, Macdonald RL. Making sense of nonsense GABA(A) receptor mutations associated with genetic epilepsies. Trends Mol Med [print-electronic]. 2009 Sep; 15(9): 430-8. PMID: 19717338, PMCID: PMC3076198, PII: S1471-4914(09)00122-1, DOI: 10.1016/j.molmed.2009.07.003, ISSN: 1471-499X.
Kang JQ, Shen W, Macdonald RL. Two molecular pathways (NMD and ERAD) contribute to a genetic epilepsy associated with the GABA(A) receptor GABRA1 PTC mutation, 975delC, S326fs328X. J. Neurosci. 2009 Mar 3/4/2009; 29(9): 2833-44. PMID: 19261879, PMCID: PMC2687144, PII: 29/9/2833, DOI: 10.1523/JNEUROSCI.4512-08.2009, ISSN: 1529-2401.
Kang JQ, Shen W, Macdonald RL. The GABRG2 mutation, Q351X, associated with generalized epilepsy with febrile seizures plus, has both loss of function and dominant-negative suppression. J. Neurosci. 2009 Mar 3/4/2009; 29(9): 2845-56. PMID: 19261880, PMCID: PMC2754234, PII: 29/9/2845, DOI: 10.1523/JNEUROSCI.4772-08.2009, ISSN: 1529-2401.
Macdonald RL, Kang JQ. Molecular pathology of genetic epilepsies associated with GABAA receptor subunit mutations. Epilepsy Curr. 2009 Jan; 9(1): 18-23. PMID: 19396344, PMCID: PMC2668111, DOI: 10.1111/j.1535-7511.2008.01278.x, ISSN: 1535-7597.
Kang JQ, Shen W, Macdonald RL. Why does fever trigger febrile seizures? GABAA receptor gamma2 subunit mutations associated with idiopathic generalized epilepsies have temperature-dependent trafficking deficiencies. J. Neurosci. 2006 Mar 3/1/2006; 26(9): 2590-7. PMID: 16510738, PII: 26/9/2590, DOI: 10.1523/JNEUROSCI.4243-05.2006, ISSN: 1529-2401.
Feng HJ, Kang JQ, Song L, Dibbens L, Mulley J, Macdonald RL. Delta subunit susceptibility variants E177A and R220H associated with complex epilepsy alter channel gating and surface expression of alpha4beta2delta GABAA receptors. J. Neurosci. 2006 Feb 2/1/2006; 26(5): 1499-506. PMID: 16452673, PII: 26/5/1499, DOI: 10.1523/JNEUROSCI.2913-05.2006, ISSN: 1529-2401.
Macdonald RL, Kang JQ, Gallagher MJ, Feng HJ. GABA(A) receptor mutations associated with generalized epilepsies. Adv. Pharmacol. 2006; 54: 147-69. PMID: 17175814, ISSN: 1054-3589.
Chong ZZ, Kang J, Li F, Maiese K. MGluRI targets microglial activation and selectively prevents neuronal cell engulfment through Akt and caspase dependent pathways. Curr Neurovasc Res. 2005 Jul; 2(3): 197-211. PMID: 16181114, PMCID: PMC1986675, ISSN: 1567-2026.
Macdonald RL, Gallagher MJ, Feng HJ, Kang J. GABA(A) receptor epilepsy mutations. Biochem. Pharmacol. 2004 Oct 10/15/2004; 68(8): 1497-506. PMID: 15451392, PII: S0006-2952(04)00543-X, DOI: 10.1016/j.bcp.2004.07.029, ISSN: 0006-2952.
Kang JQ, Macdonald RL. The GABAA receptor gamma2 subunit R43Q mutation linked to childhood absence epilepsy and febrile seizures causes retention of alpha1beta2gamma2S receptors in the endoplasmic reticulum. J. Neurosci. 2004 Oct 10/6/2004; 24(40): 8672-7. PMID: 15470132, PII: 24/40/8672, DOI: 10.1523/JNEUROSCI.2717-04.2004, ISSN: 1529-2401.
Chong ZZ, Kang JQ, Maiese K. AKT1 drives endothelial cell membrane asymmetry and microglial activation through Bcl-xL and caspase 1, 3, and 9. Exp. Cell Res. 2004 Jun 6/10/2004; 296(2): 196-207. PMID: 15149850, PII: S0014482704000497, DOI: 10.1016/j.yexcr.2004.01.021, ISSN: 0014-4827.
Chong ZZ, Kang JQ, Maiese K. Essential cellular regulatory elements of oxidative stress in early and late phases of apoptosis in the central nervous system. Antioxid. Redox Signal. 2004 Apr; 6(2): 277-87. PMID: 15025929, DOI: 10.1089/152308604322899341, ISSN: 1523-0864.
Kang JQ, Chong ZZ, Maiese K. Akt1 protects against inflammatory microglial activation through maintenance of membrane asymmetry and modulation of cysteine protease activity. J. Neurosci. Res. 2003 Oct 10/1/2003; 74(1): 37-51. PMID: 13130504, DOI: 10.1002/jnr.10740, ISSN: 0360-4012.
Chong ZZ, Lin SH, Kang JQ, Maiese K. The tyrosine phosphatase SHP2 modulates MAP kinase p38 and caspase 1 and 3 to foster neuronal survival. Cell. Mol. Neurobiol. 2003 Oct; 23(4-5): 561-78. PMID: 14514016, ISSN: 0272-4340.
Kang JQ, Chong ZZ, Maiese K. Critical role for Akt1 in the modulation of apoptotic phosphatidylserine exposure and microglial activation. Mol. Pharmacol. 2003 Sep; 64(3): 557-69. PMID: 12920191, PII: 64/3/557, DOI: 10.1124/mol.64.3.557, ISSN: 0026-895X.
Chong ZZ, Kang JQ, Maiese K. Erythropoietin: cytoprotection in vascular and neuronal cells. Curr Drug Targets Cardiovasc Haematol Disord. 2003 Jun; 3(2): 141-54. PMID: 12769640, ISSN: 1568-0061.
Chong ZZ, Kang JQ, Maiese K. Apaf-1, Bcl-xL, cytochrome c, and caspase-9 form the critical elements for cerebral vascular protection by erythropoietin. J. Cereb. Blood Flow Metab. 2003 Mar; 23(3): 320-30. PMID: 12621307, ISSN: 0271-678X.
Chong ZZ, Kang JQ, Maiese K. Erythropoietin fosters both intrinsic and extrinsic neuronal protection through modulation of microglia, Akt1, Bad, and caspase-mediated pathways. Br. J. Pharmacol. 2003 Mar; 138(6): 1107-18. PMID: 12684267, PMCID: PMC1573758, DOI: 10.1038/sj.bjp.0705161, ISSN: 0007-1188.
Chong ZZ, Lin SH, Kang JQ, Maiese K. Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8. J. Neurosci. Res. 2003 Mar 3/1/2003; 71(5): 659-69. PMID: 12584724, DOI: 10.1002/jnr.10528, ISSN: 0360-4012.
Chong ZZ, Kang JQ, Maiese K. Metabotropic glutamate receptors promote neuronal and vascular plasticity through novel intracellular pathways. Histol. Histopathol. 2003 Jan; 18(1): 173-89. PMID: 12507297, ISSN: 0213-3911.
Kenneth Maiese, Zhaozhong Chong, Jing-Qiong Kang, et. al. ISBN10: 140207400X ISBN13: 9781402074004 Cover: Hardcover. Neuronal and Vascular Plasticity: Elucidating Basic Cellular Mechanisms for Future Therapeutic Discovery. [place unknown: publisher unknown]; 2003.
Chong ZZ, Kang JQ, Maiese K. Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation. 2002 Dec 12/3/2002; 106(23): 2973-9. PMID: 12460881, ISSN: 1524-4539.
Chong ZZ, Kang JQ, Maiese K. Angiogenesis and plasticity: role of erythropoietin in vascular systems. J. Hematother. Stem Cell Res. 2002 Dec; 11(6): 863-71. PMID: 12590701, DOI: 10.1089/152581602321080529, ISSN: 1525-8165.
Chong ZZ, Kang JQ, Maiese K. Hematopoietic factor erythropoietin fosters neuroprotection through novel signal transduction cascades. J. Cereb. Blood Flow Metab. 2002 May; 22(5): 503-14. PMID: 11973422, DOI: 10.1097/00004647-200205000-00001, ISSN: 0271-678X.