How do young people develop cancer? Most have not lived long enough to accumulate mutations due to aging or environmental exposure. And most do not have any apparent cancer predisposition from inheritance of cancer-causing gene mutations. Recently, my laboratory has discovered an unanticipated cause of human cancer, resulting from the aberrant activity of the PGBD5 DNA transposase that can promote rearrangements of human genes. We reason that PGBD5 is normally controlled to promote development of healthy cells in early life, but becomes dysregulated in cells that give rise to tumors in children and young adults (Henssen et al, Elife 2015, BMC Genomics 2016, Nature Genetics 2017, Science Translational Medicine 2017, Journal of Clinical Investigation 2018).
We have now developed tools to model this activity in living cells and animals, and planned studies seek to elucidate the mechanisms by which PGBD5 causes cancer in accurate laboratory models using improved methods for human genome mapping. In turn, this knowledge will be used to develop new therapies to treat refractory human cancers, caused by similar cancerous “jumping genes.” Ultimately, this will not only enable us to understand how cancer can affect young people, but also consider potential strategies for its prevention.
We are looking for an ambitious post-doctoral research fellow to join our laboratory to investigate the molecular activities and functions of PGBD5, including its cellular co-factors, dynamics in cells and chromatin, and signaling pathways that control its activity. An ideal candidate has experience with protein biochemistry, molecular and cell biology, including specific research in DNA nucleases and chromatin biology. Please visit http://alexkentsis.net/projects/dna-transposition-genomic-plasticity/ for more information about this research and our laboratory at the Sloan Kettering Institute in the middle of vibrant New York City.
Excellent communication and project management skills are essential. Please send a cover letter describing your interests, and 3 letters of reference to Alex Kentsis, MD, PhD.