Research Assistant Professor, Department of Genetics
The main research interests are identifying the susceptibility genes and variants of human complex and rare diseases using combined information of genome-wide DNA variation, gene expression and epigenomic, and further validate using in vitro and in vivo methods.
Velo-cardio-facial syndrome (VCFS), also known as DiGeorge syndrome, Shprintzen syndrome, and 22q11 deletion syndrome (22q11DS), is caused by a deletion of a small segment of the long arm of chromosome 22. It is the most common microdeletion syndrome in humans. The severity of the syndrome varies greatly. One of my current project is to determine whether sequence variants in the genes we identify could modify the phenotype in human 22q11DS patients. TBX1 is a major cardiovascular gene on chr22q11 deletion region, but previous study suggested that the common variations in TBX1 gene are not associated with cardiovascular defects in this syndrome. A genome-wide association study (GWAS) was performed to find genetic modifiers of cardiovascular anomalies on 22q11DS subjects. The causative genes identified in this study will be functional validated using zebrafish and mouse model. The causative variants in those genes will be identified through target capture and next-generation sequencing.
The Pima Indians of Arizona have the highest reported prevalence of type 2 diabetes mellitus (T2DM) of any population in the world. They are also a very obese population. Studies have shown that both T2DM and obesity are heritable diseases. My previous work, together with Dr. Leslie Baier, excluded TCF7L2, which has been strongly associated with T2DM risk in Caucasian populations, as a major risk for T2DM among the Pima Indian population. However, KCNQ1 which was reported as the major T2DM gene in Asian was strongly associated with T2D in Pima Indian. Further GWAS identified NFIB (Nuclear factor 1 B-type) as a Pima Indians population specific obesity gene, and further in vitro functional studies suggested that NFIB could potentially affect adiposity via the lipolysis pathway. Ongoing studies in cells and mice seek to better understand the function of NFIB and its role in the development of obesity. Efforts towards understanding the role of NFIB in lipolysis pathway could help us develop a new therapeutic for obesity, T2DM and hyperlipidemia.
A. Article Published:
1. Yan Dong, Tingwei Guo, Michael Traurig, Clint C. Mason, Sayuko Kobes, Jessica Perez, William C. Knowler, Clifton Bogardus, Robert L. Hanson, Leslie J. Baier. SIRT1 is Associated with a Decrease in Acute Insulin Secretion and a Sex Specific Increase in Risk for Type 2 Diabetes in Pima Indians. Molecular Genetics and Metabolism. (In press).
2. Guo T, McGinn DM, Blonska A, Shanske A, Bassett A, Chow E, Bowser M, Sheridan M, Beemer F, Devriendt K, Swillen A, Breckpot J, Digilio MC, Marino B, Dallapiccola B, Carpenter C, Zheng X, Johnson J, Chung J, Higgins AM, Philip N, Simon TJ, Coleman K, Heine-Suner D, Rosell J, Kates W, Devoto M, Goldmuntz E, Zackai E, Wang T, Shprintzen R, Emanuel B, Morrow B; the International Chromosome 22q11.2 Consortium. Genotype and Cardiovascular Phenotype Correlations with TBX1 in 1,022 Velo-Cardio-Facial/DiGeorge/22q11.2 Deletion Syndrome Patients. Hum Mutat. 2011 Jul 27.
3. Alkalay AA, Guo T, Montagna C, Digilio MC, Dallapiccola B, Marino B, Morrow B. Genetic dosage compensation in a family with velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome. Am J Med Genet A. 2011 Mar;155(3):548-54.
4. Xu M, Xing Q, Li S, Zheng Y, Wu S, Gao R, Yu L, Guo T, Yang Y, Liu J, Zhang A, Zhao X, He G, Zhou J, Wang L, Xuan J, Du J, Li X, Feng G, Lin Z, Xu Y, St Clair D, Lin Z, He L. Pharacogenetic effects of dopamine transporter gene polymorphisms on response to chlorpromazine and clozapine and on extrapyramidal syndrome in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Aug 16;34(6):1026-32.
5. Zhang R, Zhong NN, Liu XG, Yan H, Qiu C, Han Y, Wang W, Hou WK, Liu Y, Gao CG, Guo TW, Lu SM, Deng HW, Ma J. Is the EFNB2 locus associated with schizophrenia? Single nucleotide polymorphisms and haplotypes analysis. Psychiatry Res. 2010 May 18..
6. Zhang R, Lu SM, Qiu C, Liu XG, Gao CG, Guo TW, Valenzuela RK, Deng HW, Ma J. Population-based and family-based association studies of ZNF804A locus and schizophrenia. Mol Psychiatry. 2010 May 11.
7. Ma J, Sun J, Zhang H, Zhang R, Kang WH, Gao CG, Liu HS, Ma XH, Min ZX, Zhao WX, Ning QL, Wang SH, Zhang YC, Guo TW, Lu SM. Evidence for transmission disequilibrium at the DAOA gene locus in a schizophrenia family sample. Neurosci Lett. 2009 Sep 22;462(2):105-8.
8. Guo T, Hanson RL, Traurig M, Li Muller Y, Ma L, Mack J, Kobes S, Knowler WC, Bogardus C, Baier LJ. TCF7L2 is Not a Major Susceptibility Gene for Type 2 Diabetes in Pima Indians: An Analysis of 3501 Individuals. Diabetes. 2007 Dec;56(12):3082-8
9. Liu Y, Shi Y, Guo T, Gao J, Qin W, Li S, Tang W, Feng G, Zhu S, Liu H, He L., No association between the Nuclear Receptor Coactivator 7 gene and schizophrenia in the Chinese Han population. Schizophr Res. 2007 Jan;89 (1-3):360-1.
10. TW Guo, FC Zhang, MS Yang, XC Gao, L Bian, SW Duan, ZJ Zheng, JJ Gao, HY Wang, RL Li, GY Feng, David St Clair and L He, Positive Association of the DIO2 (Deiodinase Type 2) Gene with Mental Retardation in the iodine-deficient areas of China，J Med Genet 41: 585-590
11. Ting-wei Guo, Fu-chang Zhang, Maosheng Yang , Xiao-cai Gao, Li Bian, Qian Ji,，Jie Ma, Jianjun Gao，Zi-jian Zheng, Rui-lin Li,Guo-yin Feng , Lin He, Lack of association of the thyroid transcription factor 1 gene with mental retardation in the iodine-deficient areas of China, Psychiatr Genet. 2005 Dec;15(4):233.
12. Guo TW, Zhang FC, Gao JJ, Bian L, Gao XC, Ma J, Yang M, Ji Q, Duan SW, Zheng ZJ, Li RL, Feng GY, St Clair D, He L. Polymorphisms in the TSHR (thyrotropin receptor) gene on chromosome 14q31 are not associated with mental retardation in the iodine-deficient areas of China. Neurosci Lett. 2005 Jul 1-8;382(1-2):179-84.
13. Xu MQ, Xing QH, Zheng YL, Li S, Gao JJ, He G, Guo TW, Feng GY, Xu F, He L. Association of AKT1 gene polymorphisms with risk of schizophrenia and with response to antipsychotics in the Chinese population. J Clin Psychiatry. 2007 Sep;68(9):1358-67.
14. J Ma, W Qin, X Y Wang, T W Guo, L Bian, S W Duan, X W Li, F G Zou, Y R Fang, J X Fang, G Y Feng, N F Gu, D St Clair, L He, Further evidence for the association between G72/G30 genes and schizophrenia in two ethnically distinct populations, Molecular Psychiatry 11, 479 - 487 (01 May 2006)
15. Sun Y, Zhang F, Gao J, Gao X, Guo T, Zhang K, Shi Y, Zheng Z, Tang W, Zheng Y, Li S, Li X, Feng G, Shen X, He L. Positive association between POU1F1 and mental retardation in young females in the Chinese Han population. Hum Mol Genet. 2006 Apr 1;15 (7):1237-43.
16. Sun Y, Zhang F, Gao J, Gao X, Guo T, Shi Y, Tang W, Li S, Zheng Z, Zheng Y, Li X, Feng G, He L. Variants in the RAB3A gene are not associated with mental retardation in the Chinese population.Neurosci Lett. 2006 Jun 19;401(1-2):114-8.
17. Gao J, Gao X, Qin W, Dang F, Zhang F, Qian X, Zeng X, Xing Q, Zheng Z, Li J, Guo T, Chang H, Feng G, He L. No observable relationship between the ACE gene insertion/deletion polymorphism and psychometric IQ and psychomotor ability in Chinese children. Neuropsychobiology. 2006;53(4):196-202.
18. Bian L, Yang JD, Guo TW, Duan Y, Qin W, Sun Y, Feng GY, He L. Association Study of the A2M and LRP1 Genes with Alzheimer Disease in the Han Chinese. Biol Psychiatry. 2005 Nov 1; 58(9):731-7.
19. Liu J, Shi Y, Tang J, Guo T, Li X, Yang Y, Chen Q, Zhao X, He G, Feng G, Gu N, Zhu S, Liu H, He L. SNPs and haplotypes in the S100B gene reveal association with schizophrenia. Biochem Biophys Res Commun. 2005 Mar 4;328(1):335-41.
20. Duan S, Yin H, Chen W, Xing Q, chen Q, Guo T, Gao J, Li X, Gao R, Liu Z, Gu N, Feng G, He L. No association between the serotonin 1B receptor gene and schizophrenia in a case-control and family-based association study. Neurosci Lett. 2005 Mar 11;376(2):93-7.
21. Liu J, Shi Y, Tang W, Guo T, Li D, Yang Y, Zhao X, Wang H, Li X, Feng G, Gu N, Zhu S, Liu H, Guo Y, Shi J, Sang H, Yan L, He L. Positive association of the human GABA-A-receptor beta 2 subunit gene haplotype with schizophrenia in the Chinese Han population. Biochem Biophys Res Commun. 2005 Sep 2;334(3):817-23.
22. Gao J, Zhang F, Guo T, Gao X, Duan S, Wang H, Zheng Z, Huang T, Feng G, St Clair D, He L. Distribution of apolipoprotein E allele frequencies of the Han Chinese in an iodine-deficient mountainous area. Ann Hum Biol. 2004 Sep-Oct;31(5):578-85.
23. L Bian, JD Yang, TW Guo, Y Sun, SW Duan, WY Chen, YX Pan, GY Feng, L He, Insulin-degrading enzyme and Alzheimer’s: a genetic association study in the Han Chinese，Neurology ; 63: 241
24. Shiwei Duan, Yifeng Xu, Wuyan Chen, Zhuangjun Liu, Tingwei Guo, Jianjun Gao, Li Bian, Yonglan Zhen, Xiuxia Li, Xiaoju Zhang, Chao Li, Yuxi Pan, Niufan Gu, Guoyin Feng，Lin He, No association between the promoter variants of tumor necrosis factor alpha (TNFα) and schizophrenia in Chinese Han population. Neurosci Lett. 2004 Aug 12;366(2):139-43.
25. M S Yang, L Yu, T W Guo, S M Zhu, H J Liu, Y Y Shi, N-F Gu, G Y Feng, L He, Evidence for association between single nucleotide polymorphisms in T complex protein 1 gene and schizophrenia in the Chinese Han population, J Med Genet 2004;41:e63.
26. Yang Lin, Guo Ailian, He Jun, Guo Tingwei. A study on lignin degradation for the use of corn stalk, Journal of Northwest University (Natural Science Edition) (Chinese). Aug. 2001, Vol. 31 No. 4
27. Guo Ailian,Guo Tingwei,Yang Lin,Zhao Jianshe:Enzymatic Study on Species Isolation from Nature to Secrete Active Raw-Starch Glycoamylase, FOOD SCIENCE (Chinese), 2001 Vol.22 No.10
28. Guo Ailian, Guo Tingwei, Sun Xianfeng, Yang Lin, He Jun, Screening of high raw-starch Glucoamlase producing strain by UV and He-Ne Laser irradiation and its application. ACTA PHOTONICA SINICA (Chinese) Vo1128 No19, September 1999
29. Guo Ailian, Guo Tingwei, Zhu Hongli,Lang Huiyun,Ma Hongjun.(1999) He-Ne Laser treated of the protoplast from aspergillus Niger Sx, ACTA PHOTONICA SINICA (Chinese),Vo1128, No 17, July 1999
30. Guo Tingwei, Guo Ailian, Yanglin. Studies of isolation and fermentation condition of Raw-starch glucoamylase producing strain, China Brewing (Chinese), 1998 (6):15-17
B. Book Chapter:
Tingwei Guo, David St Clair, and Lin He. 2008 “The DIO2 (deiodinase type 2) gene and mental retardation in iodine-deficiency” in Comprehensive Handbook on Iodine: Nutritional, Endocrine and Pathological Aspects, Profs Victor R Preedy, Gerard N. Burrow & Ronald Ross Watson (Publisher: Elsevier).
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Albert Einstein College of Medicine
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