Taosheng Huang, M.D., Ph.D.
Assistant Professor (joint appt.)

University of California
314 Sprague Hall
Irvine, CA 92697

Tel: (949) 824-9346
Fax: (949) 824-9776
Email: huangts@uci.edu
Website: Lab Homepage

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