| Titia de Lange, Ph.D. is the Leon Hess Professor and Head of the Laboratory of Cell Biology and Genetics at The Rockefeller University, New York. Dr. de Lange is a recognized world leader in the field of telomere biology. |
 |
Importantly, she is also a dedicated mentor and strong advocate of young female scientists. The overarching goal of her research is to understand how the human telomeric protein:DNA complex executes its two essential functions: to protect chromosome ends and mediate their replication. Telomeres shield chromosome ends from extensive degradation and chromosomal fusion, thereby preventing cellular senescence and transformation. Her research is aimed at determining how cells distinguish natural chromosome ends from DNA breaks and the health impact when telomere protection is lost, including cancer and accelerated aging. To this end, the Dr. de Lange laboratory was the first to demonstrate the |
| T-loop structure of telomeres and identified the majority of the proteins that bind telomeres creating the shelterin complex that protects chromosome ends. Importantly, telomeric DNA is particularly vulnerable to DNA damage and numerous DNA repair proteins are integral parts of the shelterin complex. Thus elucidating the mechanism by which telomeres contribute to genome stability is critical for understanding how cells and organisms respond to environmental genotoxic stress. |
|
| Keith Caldecott, Ph.D. is a Professor of Biochemistry in the Genome Damage and Stability Centre at the University of Sussex, England. Dr. Caldecott is recognized worldwide as a leader in discovering the mechanism |
 |
by which DNA single-strand breaks (SSBs), one of the most abundant lesions in mammalian cells, are repaired. His laboratory was instrumental in characterizing the role of XRCC1, TDP1, CHK1, PARP and APLF in this repair pathway. Dr. Caldecott is an exemplary role model because of his ability to utilize numerous experimental approaches from biochemistry to human genetics to identify novel DNA repair proteins and link them to human disease. As an example, Dr. Caldecott identified aprataxin, a protein that interacts with numerous BER repair proteins, as causal in ataxia oculomotor apraxia and mutations in TDP1 as causal in spinocerebellar ataxia with axonal neuropathy. This work provides direct evidence that DNA |
| damage, and in particular unrepaired SSBs, causes neurodegeneration, a major health challenge with both a genetic and environmental component. |
|
