Professor, Department of Cell Biology
Chanin Bldg., Room 416
Our laboratory is a part of the Einstein Center for Human Embryonic Stem Cell Research and the Cancer Center.
The main interest of our lab is how the DNA replication program in mammalian cells is organized and regulated. We are currently focused on understanding the role of genomic instability at human chromosomal fragile sites in cancer, aging disorders related to trinucleotide repeat expansion, telomere replication and reprogramming of DNA replication in human embryonic stem (ES) cells.
Genome instability that occurs in the early development of many cancers and other diseases is thought to be caused by replication fork stalling. This is clinically relevant since most current cancer therapies are based on radiation or chemotherapeutic agents that stall or block forks. Manipulating cellular responses to fork stalling may therefore prove crucial in improving effectiveness of current chemotherapies.
• Role of common fragile sites in human cancer and cancer prone disorders such as Fanconi anemia.
• Triplet nucleotide expansion diseases and aging.
• Genome protection by telomeres.
• Regulation and reprogramming of DNA replication of human embryonic stem (ES) cells and induced pluripotent stem cells (iPS).
Current projects include a wide range of interests:
• Mechanisms leading to breaks at common fragile sites that result in chromosomal rearrangements frequently detected in cancer cells.
• Determining whether common fragile site instability is causative in predisposing individuals with Fanconi anemia to cancer.
• Understanding trinucleotide repeat expansion and telomere maintenance to gain insights into aging related disorders.
• Triplet nucleotide expansion diseases. The fragile X premutation expansion to 55 – 200 CGGs affects ~ one in 200 women resulting in serious fertility problems and ataxia.
• Defining mechanisms that ensure proper telomere replication to prevent telomere dysfunction that results in cellular senescence and cancer-promoting genetic instability
• Study of human ES cell DNA replication dynamics. Thorough understanding of replication programs to advance the availability of immunologically compatible hES cells for patients.