University of Southern California

USC Neuroscience

Kai Wang

Assistant Professor, Psychiatry and Preventive Medicine; Member, Zilkha Neurogenetic Institute and Norris Comprehensive Cancer Center

Research Topics

  1. Bioinformatics approaches for high-throughput sequencing data
  2. Genomic analysis of brain disorders

Research Overview

1. Develop bioinformatics and computational biology methods to handle high-throughput genomics data sets, especially next-generation sequencing data. Previously, we have worked on SNP arrays and developed the PennCNV software for identifying copy number variations (CNVs) and the GenGen software for pathway-based association tests. Recently, we focused on whole-genome and whole-exome sequencing data, and developed the ANNOVAR software for functional annotation of genetic variants. With DNA and RNA sequencing data, we are developing methods to identify genetic variants (SNPs and CNVs), annotate variants, impute variants, infer expression level, identify somatic mutations, and perform association tests on genes, genomic regions and biological pathways.

2. Apply genomic approaches to a variety of brain disorders, especially brain cancer and neurodevelopmental diseases. I am currently collaborating with several colleagues at USC to examine brain disorders using high-throughput genomics approaches. For example, neurodevelopmental and neuropsychiatric diseases may result from perturbations of the nervous system, but it is extremely difficult to manipulate or interrogate this system in vivo in humans. Together with colleagues at the USC Broad CIRM center, we are establishing a stem cell model to identify genetic networks that link genetic risk to functional understanding of developmental processes. More importantly, the cellular system may be expanded to determine the functional impact of genetic lesions in other human diseases, or be used for personalized disease characterization and for optimization of therapeutic strategies. We are also interested in identifying genetic factors responsible for malignant transformation of meningioma and other brain tumors. Meningiomas are the most frequently diagnosed primary brain tumors, and can be broadly classified as benign versus anaplastic (malignant). The malignant tumors constitute ~3% of all meningiomas. However, little is known on what genes cause malignant transformation, and this will ultimately delay the development of effective treatment or prognosis strategies. Together with several colleagues at the Department of Neurosurgery, we will use high-throughput DNA and RNA sequencing approaches to identify somatic mutations, copy number alternations, fusion genes and splicing isoforms that make meningiomas become malignant, and test the therapeutic potential of targeted knockdown of gain-of-function mutations.

Contact Information

Web Sites:
Lab Website
ANNOVAR
PennCNV
E-mail:
kaiwang@usc.edu
Mailing Address:
1501 San Pablo Street
ZNI 221
Los Angeles, CA 90089
Office Location:
ZNI 245
Office Phone:
(323) 442-3917
Lab Location:
ZNI 221
Lab Phone:
(323) 442-3785
Fax:
(323) 442-2145

Education

  • B.S., Peking University, 2000
  • Ph.D., University of Washington, 2005
  • Postdoc, University of Pennsylvania and Children's Hospital of Philadelphia, 2010

Selected Publications

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Chen G, Chang X, Curtis C, Wang K. Precise inference of copy number alterations from SNP arrays. Bioinformatics, in press, 2013

Gao F, Ling C, Shi L, Commins D, Zada G, Mack W, Wang K. Inversion-mediated gene fusions involving NAB2-STAT6 in an unusual malignant meningioma. British Journal of Cancer, in press

Wang K, Kim C, Bradfield J, Guo Y, Toskala E, Otieno FG, Hou C, Thomas K, Cardinale C, Lyon GL, Golhar R, Hakonarson H. Whole-genome DNA/RNA sequencing on a novel Mendelian disease with neuromuscular and cardiac involvement.Genome Medicine, in press

Gao F, Lin E, Feng Y, Mack WJ, Shen Y, Wang K. Characterizing immunoglobulin repertoire from whole blood by a personal genome sequencer. PLoS ONE, in press

Mills JA, Wang K, Paluru PC, Ying L, Lu L, Galvao AM, Xu D, Yao Y, Sullivan SK, Sullivan L, Mac H, Omari A, Jean JC, Shen S, Grower A, Spira A, Mostoslavsky G, Kotton DN, French DL, Weiss MJ, Gadue P. Clonal Genetic and Hematopoietic Heterogeneity among Human Induced Pluripotent Stem Cell lines. Blood, in press

Gao F, Wei Z, Lu W*, Wang K*. Comparative analysis of 4C-Seq data generated from enzyme-based and sonicaion-based methods. BMC Genomics, 14:345, 2013 -PubMed

Shi L, Chang X, Zhang P, Coba M, Lu W, Wang K. The functional genetic link of NLGN4X knockdown and neurodevelopment in neural stem cells. Human Molecular Genetics, in press -PubMed

Wei Z, Gao F, Kim S, Yang H, Wang K, Lu W. Interchromosomal interactions modulate Oct4 expression in reprogramming and self-renewal. Cell Stem Cell, in press

Shi L, Zhang X, Golhar R, Otieno FG, He M, Hou C, Kim C, Keating B, Lyon GL, Wang K*, Hakonarson H*. Whole-genome sequencing in an autism multiplex family. Molecular Autism, 4:8, 2013

O'Rawe J, Jiang T, Sun G, Wu Y, Wang W, Hu J, Bodily P, Tian L, Hakonarson H, Johnson WE, Wei Z, Wang K*, Lyon GJ*. Low concordance of multiple variant calling pipelines on human exomes and genomes. Genome Medicine, 5:28, 2013

Gao F, Wei Z, Woo A, Wang K*, Lu W*. The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells. Scientific Reports, 3:1588, 2013

Zeng L, Zhang P, Shi L, Yamamoto V, Lu W*, Wang K*. Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models. PLoS ONE, 8:e59685, 2013

Chang X, Xu T, Li Y, Wang K. Dynamic modular architecture of protein-protein interaction networks beyond the dichotomy of 'date' and 'party' hubs. Scientific Reports, 3:1691, 2013

Gao F, Shi L, Russin J, Zeng L, Chang X, He S, Chen TC, Giannotta SL, Weisenberger DJ, Zada G, Mack WJ, Wang K. DNA Methylation in the Malignant Transformation of Meningiomas. PLoS ONE, 8:e54114, 2013

Lyon GJ, Wang K. Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress. Genome Medicine, 4:58, 2012 -PubMed

Qiu S, Luo S, Evgrafov O, Li R, Schroth GP, Levitt P, Knowles JA, Wang K. Single-neuron RNA-Seq: technical feasibility and reproducibility. Frontiers in Genetics, 3:124, 2012 -PubMed

Chang X, Wang K. wANNOVAR: annotating genetic variants for personal genomes via the web. Journal of Medical Genetics. 49:433-436, 2012 -PubMed