Taosheng Huang, M.D., Ph.D.

Molecular basis of genetic diseases in human – The primary interest of my lab is to study the molecular basis of genetic syndromes and to apply the discoveries from rare diseases to common conditions. Currently, we are focusing on the following areas:

The role of TBX3 in breast cancer TBX3 is a T-box transcription factor. Mutation of TBX3 causes Ulnar-Mammary syndrome, which is characterized by hypoplasia and absence of the mammary gland. We were one of the first groups to show that overexpression of TBX3 plays an important role in breast cancer. We have analyzed TBX3 expression in human breast cancer tissue. The TBX3 expression levels were compared with those of matched normal tissues from the same individual and correlated with other established biomarkers. Our study shows that TBX3 is overexpressed in primary breast cancer tissues. Mechanistically, we found that TBX3 interacts with HDACs and inhibit the downstream target gene expression. In addition, we found TBX3 regulates a large group of genes in breast cancer. Our current research aims to optimize the clinical relevance of this data and we work with animal and breast cancer tissues in parallel.

The Genetic basis of optic atrophy We have identified many families with autosomal dominant inherited optic atrophy. We reported that some mutations of the OPA1 gene can cause a sex-influenced phenotype; the males are more severely affected and have an earlier onset as compared to the female members of the family. This human study leads to another interesting discovery. In collaboration with Dr. Arnold Star in the Department of Neurology, we found the OPA1 mutation H445R causes loss of vision and hearing. Using electrophysiological analysis, we found that this mutation causes asynchronous cochlear conduction and this suggests a novel mechanism of optic atrophy. To study the function of OPA1 and the molecular mechanisms of optic atrophy, we created a drosophila model for OPA1. We found that homozygous OPA1 knockout was lethal, but we circumvented this by generating a somatic mutation with an eye flipase. In adult flies, the dOpa1 somatic mutation caused an increase in reactive oxygen species (ROS) production and mitochondrial fragmentation, and these were associated with loss of and damage to the cone and pigment cells. Our group went on to show that antioxidants can partially reverse the glossy eye phenotype, further suggesting that ROS play an important role in cone and pigment cell death. Together, these results show dOpa1 mutations cause cell loss by two distinct pathogenic pathways. This study provides novel insights into the pathogenesis of optic atrophy and demonstrates the promise of antioxidants as therapeutic agents for this condition.

The TBX5 introcellular pathway TBX5 is a T-box transcription factor. Mutation of TBX5 causes Holt-Oram syndrome, which is characterized by congenital heart diseases and limb anomalies. Currently, we are working on the TBX5 introcellular pathway, including upstream transcription factors, cofactors and downstream targets. Using a combination of promoter array, siRNA knockdown, we have identified a large group of genes that are associated with cardiac development and congenital heart defects. Congenital heart disease is a most common malformation and contributes significantly to the morbidity and mortality in pediatric populations. We are in the process of analyzing the downstream targets.

Identification of the disease-causing gene associated with noncompaction of the ventricular myocardium (spongy heart). For this project, we are studying a family a balanced translocation on chromosome 11. We are also performing a linkage study for a large family with this disease. So far, we have identified a new locus on Chromosome 11 that appears to be associated with this disease. In addition, we have recruited a large patient population and we are in the process to identify the genetic cause for this condition.

Recent Publications

  • Tang S, Huang T.(2010) Characterization of mitochondrial DNA heteroplasmy using a parallel sequencing system. Biotechniques. 48(4):287-96.
  • Tang S, Batra A, Zhang Y, Ebenroth ES, Huang T.(2010) Left ventricular noncompaction is associated with mutations in the mitochondrial genome. Mitochondrion. 10(4):350-7. Epub 2010 Mar 6.
  • Huang T, Santarelli R, Starr A.(2009) Mutation of OPA1 gene causes deafness by affecting function of auditory nerve terminals. Brain Res.1300:97-104. Epub 2009 Sep 3.
  • Shahrestani P, Leung HT, Le PK, Pak WL, Tse S, Ocorr K, Huang T.(2009) Heterozygous mutation of Drosophila Opa1 causes the development of multiple organ abnormalities in an age-dependent and organ-specific manner. PLoS One. 2009 Aug 31;4(8):e6867.
  • Tang S, Le PK, Tse S, Wallace DC, Huang T.(2009) Heterozygous mutation of Opa1 in Drosophila shortens lifespan mediated through increased reactive oxygen species production. PLoS One. 2009;4(2):e4492. Epub 2009 Feb 16.
  • Will Yarosh*, Tomasa Barrientos*, Taraneh Esmailpour, Limin Lin, Philip M. Carpenter, Kathryn Osann, Hoda Anton-Culver and Taosheng Huang (2008) TBX3 is overexpressed in breast cancer and represses p14ARF by interacting with HDACs, Cancer Research, 68:693-699 *These authors contribute equally
  • Shaohua Tang, Qimin Xu, Xueqin Xu, Xiaomei Yang, Xiaoqin Wang, Nancy Speck, Taosheng Huang (2008) A novel missense mutation in the RUNX2 gene causes cleidocranial dysplasia in a Chinese family with hyperplastic nails, BMC Medical Genetics, in press
  • Will Yarosh, Jessica Monserrate, James Jiayuan Tong, Diane Le, Kimberly Nguyen, Carrie Brachmann Douglas Wallace, Taosheng Huang (2008) The Molecular Mechanisms of OPA1-Mediated Optic Atrophy in Drosophila Model and Prospects for Antioxidant Treatment, PLoS Genetics, 2008 Jan;4(1):e6.
  • Hongfei Pan, Guifang Long, Qiang Li, Yanni Feng, Zhiying Lei, Hongwei Wei, Yueyan Huang, Jinghong Huang, Na Lin, Qunqing Xu, Shaiyong Ling, Xiajing Chen, Taosheng Huang (2007) Current Status of Thalassemia in Minority Populations in Guanxi, China, Clinical Genetics, 71: 419–426
  • Taosheng Huang Jong-Dae Whang, Virginia Kimonis. Sex-Influenced Autosomal Dominant Optic Atrophy is Caused by Mutations of IVS9 +2A>G in The OPA1 Gene, Genetics in Medicine, 8(1):59. 2006.

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