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Research: Center of Excellence for Neuroscience

Principal Investigators

Dr.Xu

Assistant Professor

Human Molecular Genetics and Pharmacogenetics for Neuropsychiatric Disorders

email: chun.xu@ttuhsc.edu

   

Dr. Chun Xu received her MD and master degree from the Harbin Medical University, China as well as her PhD from the Karolinska Institute, Stockholm, Sweden. She has an outstanding background in molecular genetics for neuropsychiatric disorders, pharmacogenetics/pharmacogenomics, nutrigenetics/nutrigenomics, cancer genetics, and immune-genetics. After completing my PhD in Neuroscience and neurogenetics, her achievements included: Confirmation of linkage of the dopamine transporter locus to attention-deficit/hyperactivity disorder (Xu et al., 2001); Exclusion mapping of adrenergic receptors a2A and a1C in Tourettes Syndrome (Xu et al., 2003); Pharmacogentics study: Identification and characterization of a novel polymorphism of CYP2A6 gene which alters nicotine activity in vivo in tobacco dependency (Xu et al., 2002); Demonstration of strong association of TRPM2 and NDUFV2 variants with bipolar disorder using both population-based association and family-based association (Xu et al., 2006, 2008 and 2009); a genome-wide-association (GWA) study, replication, and combined analyses of primary biliary cirrhosis using 373,400 SNPs on the Illumina 370 HapMap BeadChip (Xu et al. the New England of Journal Medicine, 2009 and Nature Genetics 2010). Her basic research has been funded by a number of Canadian research foundations and NARSAD.

The primary goal of Dr. Chun Xu’s research is to identify susceptibility genes for neuropsychiatric diseases and medication treatment outcome, including schizophrenia (SC), bipolar disorder (BP), dementia, attention deficit hyperactivity disorder (ADHD), and epilepsy. The laboratory of neuropsychiatric genetics/genomics and pharmacogenetics/pharmacogenomics will continue the long-standing basic research program of the PI to define the genetic architecture, epigenetic profile, and environmental sources of the most severe and heritable neuropsychiatric disorders in collaboration with faculty members of the Texas Tech University Health Sciences Center as well as national and international collaboration.

 

Studies are ongoing in the areas of:

 

     1) Large scale genome-wide association studies (GWAS) on BP, SC

     2) Replication study based on GWAS signals

     3) Biological follow-up of candidate genes and pathway-based analysis

     4) Genetic risk prediction

     5) Rare variant identification by next generation sequencing technology

     6) Identification of biomarkers of the disease risk and novel targets for future medication for dementia and neuropsychiatric disorders methylation sequencing.

    7) Identification of biomarkers of human longevity and healthy aging

 

Research Specialties

Behavior genetics, pharmacogenetics, and human molecular genetics.

 

Selected Publications

1.  Liu X, Invernizzi P, Lu Y, Kosoy R, Lu Y, Bianchi I, Podda M, Xu C et al, Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat Genet. 2010 Aug;42:658-60.

2.  Hirschfield GM, Liu X, Han Y, Gorlov IP, Lu Y, Xu C et al, Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis. Nat Genet. 2010 Aug;42:655-7.

3. Hirschfield GM Liu, Xu C, Lu Y, Xie G, Lu Y, Gu X, Walker EJ, Jing K, Juran BD BSc, Mason AL, Myers RP, Peltekian KM, Ghent CN, Coltescu C, Atkinson EJ , Heathcote EJ, Lazaridis KN, Amos CI, Siminovitch KA (2009). Genomewide association analysis identifies HLA, IL12A and IL12RB2 as risk loci for primary biliary cirrhosis. New England Journal of Medicine 360 (24):2544-55

4. Li C, Li X, Miao Y, Wang Q, Jiang W, Xu C et al., (2009) SubpathwayMiner: a software package for flexible identification of pathways.  Nucleic Acids Research  37 (19) e131

5. Walker EJ, Hirschfield GM, Xu C, Lu Y, Liu X, Lu Y, Coltescu C, Wang K, Newman WG, Bykerk V, Keystone EC, Mosher D, Amos CI, Heathcote EJ, Siminovitch KA (2009) CTLA4/ICOS gene variants and haplotypes are associated with rheumatoid arthritis and primary biliary cirrhosis in the Canadian population. Arthritis Rheum. 2009 Apr;60(4):931-7

6. Xu C, Li PP, Cooke RG, Parikh SV, Wang K, Kennedy JL, Warsh JJ  (2009) TRPM2 variants and bipolar disorder risk: confirmation in a family-based association study. Bipolar Disord. 2009 Feb;11(1):1-10.

7. Xu C, Li P.P., Kennedy JL et al (2008) Further support for association of the mitochondrial complex I subunit gene NDUFV2 with bipolar disorder Bipolar Disorders 10:105

8. Xu C, Li P.P., Cooke R et al (2006) Genetic Evaluation of TRPM2 Variants and BD Risk:  Confirmation in a Family-Based Association Study (Am J Psychiatry, submitted).

9. Xu C, Macciardi F, Li P.P et al (2006) Association of the Putative Susceptibility Gene, Transient Receptor Potential Protein Melastatin Type 2, with Bipolar Disorder.  Am J Med.Genet. 2006;141B:36-43.

10. Xu C., Warsh J.J., Li PP et al (2005). Further Support for Association of the Mitochondrial Complex I Subunit Gene NDUFV2 with Bipolar Disorder. Biol Psychiatry, 57: 178S.

11. Xu, C., Warsh, J. J., Kennedy et al (2004). Association of the Putative Bipolar Disorder Susceptibility Gene, TRPM2, With Bipolar II Disorder. Int. Neuropsychopharm 7: S357.

12. Xu C, Ozbay F, Wigg K et al (2003) Evaluation of adrenergic receptors 2A and 1C and Gilles de la Tourette Syndrome. Am J Med Genet. May 15;119B(1):54-9

13. Xu C, Goodz S, Sellers EM et al (2002) CYP2A6 Genetic Variation and Potential Consequences. Advanced Drug Delivery Review 54, 1245-1256.

14. Xu C, Rao YS, Xu B et al (2002) A novel polymorphism in exon 9 of CYP2A6 gene alters activity in vivo. BBRC 290: 318-324

15. Dai Y, Xu C, Holmberg M et al (2001) Linkage analysis suggests a region of importance for multiple sclerosis in 3p14-13. Genes Immun.  Dec;2(8):451-4

16. Barr CL, Xu C, Kroft J, Feng Y et al (2001) Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder. Biol Psychiatry 49: 333-339

17. Xu C, Schachar R, Tannock R et al (2001) Linkage study of the a2A adrenergic receptor in attention-deficit hyperactivity disorder families. American journal of Medical Genetics (Neuropsychiatric Genetics) 105: 159-162

18. Xu C, Dai YM, Lorentzen JC et al (2001) Linkage analysis in multiple sclerosis of chromosomal regions syntenic to experimental autoimmune disease loci. Europe of Journal of Human Genetics 9: 458-463

19 Xu C, Dai YM and Jan Hillert (1999) Association and linkage analysis of candidate chromosomal regions in multiple sclerosis: indication of disease genes in 12q23 and 7 ptr-15.  Europe of Journal of Human Genetics 7(2): 110-116

20. Ligers A, Xu C Saarinen S, Oleup O, and Hillert J (1999) The CTLA-4 gene is associated with multiple sclerosis. Journal of Neuroimmunology  97: 182-190

21.  He Bin, Xu C, Yang B et al (1998) Linkage and association analysis of genes encoding cytokines and myelin proteins in multiple sclerosis. Journal of Neuroimmunology  86:13-19

22. Xu C and Jan Hillert  (1998) Absence of linkage with the neuronal nitric oxide (NOS1) gene in forty-one multiplex Swedish MS families. European of Journal Neurology 5: 393-396 

23. Anna Wedell, Xu C, et al., (1994) A steroid 21-hydroxylase allele concomitantly carrying four disease-causing mutations is not uncommon in the Swedish population. Human Genetics 93: 204-206.

24. Xu C et al., (1991) Studies on chromosomal fragile sites of the patients with GTT, cervical cancer and ovary.    Chinese Journal of Gynecology and Obstetrics 25: 157

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