Gain insights into the biochemical mechanisms underlying homologous chromosomal pairing and segregation in order to improve gene therapy.

Dr. Wu’s research has implications for gene therapy, as well as for intervention in various disease processes. The biochemical mechanisms underlying the pairing of homologous chromosomes are related to homologous recombination, a key for gene therapy. Insights into this process may lead to improvements in retroviral-mediated gene transfer. Understanding the mammalian genetic elements  that are required for chromosome pairing and segregation may have direct relevance to disease processes in which these biochemical processes go awry. The putative genomic “authenticator” function of UCEs may be critical for preventing chromosomal abnormalities, such as aneuploidy, that most likely precede or foster disease processes, such as cancer.

• Explore the biological mechanisms and consequences of chromosome homology and pairing, employing various genetic approaches.
   
• Study certain ultraconserved, genomic sequences (UCEs) and their potential role in (1) preserving chromosome intergrity and (2) suppressing copy number variants (CNVs).
   
• Extend chromosome homology studies in Drosophila to mammalian systems to probe for links between chromosome homology and   pathophysiology.
   
• Investigate the genetic and molecular processes in Drosophila and mammalian cells that facilitate homologous regions on chromosomes to find each other.  
   
• Test the hypothesis that UCEs act as cellular sentries for abnormal chromosomal pairing.
   
• Study non-random chromosomal segregation, and its potential relationship to the development of aneuploidy and disease.
   
• Develop and expand the Personal Genetics Education Project, which strives to communicate the complex ethical and clinical issues linked to personal genomic data in an easily comprehensible format that can be used in the classroom.
   
• Expand non-profit activities in the public sector that are aimed at helping students and non-scientists grasp the key issues created in the new era of personalized medicine.
   

Dr. Wu’s laboratory focuses on evolutionarily conserved, chromosomal phenomena that center around gene and chromosomal homology. Chromosomal homology affects a variety of genetic events, with a high likelihood that various disease processes may be due to aberrant chromosomal, homology-driven pairing, segregation, or both. The laboratory employed Drosophila as a model system for studying the genetics of chromosomal homology. Dr. Wu’s recently published articles cover a wide range of topics including: X-chromosome inactivation; topoisomerase II and chromosomal pairing; trans interactions between enhancers and promoters; and mammalian ultraconserved elements (UCEs). The lab’s findings clearly demonstrate the widespread occurrence of homologous chromosomal pairing in multiple cell types and throughout the cell cycle. Moreover, the data demonstrating that topoisomerase II is required for pairing, strongly suggests a highly regulated process with an important function.

The lab’s recent studies on UCEs revealed that these discrete genomic fragments, which display identity in different species, are conspicuously absent in genomic areas where there are alterations in the copy number (that is, copy number variants and segmental duplications). These findings led to the hypothesis that UCEs may be a surrogate for copy counting, in that an aberrant copy number of a UCE may trigger a signaling pathway that warns the cell of the aberrant event.
 

Biological Mechanisms and Pathways

• aneuploidy •
• Carcinoma •
• Chromosome segregation •
• Chromosome X inactivation •
• CNV •
• Copy number variant •
• Gene homology •
• Gene regulation •
• Homologue pairing •
• Personal Genetics Education Project (http://www.pged.org/) •
• Trans gene regulation •
• Transvection •
• UCE •
• Ultraconserved Elements •
• Ultraconserved Elements
•  

Cancer

• aneuploidy •
• Carcinoma
•  

Disease Mechanisms

• Carcinoma
•  

Research Tools and Instrumentation

• FISH •
• Gene therapy
•  

Therapeutic Discovery Tools and Assays

• Gene therapy
•