Paul Lerou

Research interests:

     My interests include derivation of human pluripotent stem cells and pre-implanation embryonic development. Specifically, I am interested in studying the maintenance of genomic stability in human pluripotent stem cells.
     Human embryonic stem (hES) cells are self renewing, pluripotent cells that are derived from the early embryo. The cell cycle of embryonic stem (ES) cells differs significantly from that of somatic cells. In particular, the ES cell cycle is characterized by a rapid cell cycle and short G1 phase, hyperphosphorylated Rb, constitutive cyclin E/A-CDK2 activity, and altered p53 activity. In somatic cells, such molecular alterations can result in genomic instability and tumorigenesis, yet ES cells maintain genomic stability, retain the capacity to differentiate and contribute to normal organismal development. ES cells also have capacity to self-renew indefinitely and fail to senesce. This is in contrast to somatic cells which will senesce due to erosion of telomeres and accrued DNA and cellular damage after a finite number of cell divisions. Telomere maintenance has been demonstrated in hES cells9, but the response to DNA damage has not been extensively studied. In my research, I will test the hypothesis that ES cells possess unique and specialized mechanisms to maintain genomic stability.
     To this end we are developing both live and fixed cell imaging techniques to study mitotic progression. We are also collaborating with Andrea Ballabeni, post-doctoral fellow in Marc Kirschener’s lab, to perform biomolecular analysis of the pluripotent stem cell cycle.



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		Paul Lerou, M.D. Thomas Jefferson University, Philadelphia, Pennsylvania Instructor in Pediatrics (HMS), Newborn Medicine (BWH)
		Research interests: My interests include derivation of human pluripotent stem cells and pre-implanation embryonic development. Specifically, I am interested in studying the maintenance of genomic stability in human pluripotent stem cells. Human embryonic stem (hES) cells are self renewing, pluripotent cells that are derived from the early embryo. The cell cycle of embryonic stem (ES) cells differs significantly from that of somatic cells. In particular, the ES cell cycle is characterized by a rapid cell cycle and short G1 phase, hyperphosphorylated Rb, constitutive cyclin E/A-CDK2 activity, and altered p53 activity. In somatic cells, such molecular alterations can result in genomic instability and tumorigenesis, yet ES cells maintain genomic stability, retain the capacity to differentiate and contribute to normal organismal development. ES cells also have capacity to self-renew indefinitely and fail to senesce. This is in contrast to somatic cells which will senesce due to erosion of telomeres and accrued DNA and cellular damage after a finite number of cell divisions. Telomere maintenance has been demonstrated in hES cells9, but the response to DNA damage has not been extensively studied. In my research, I will test the hypothesis that ES cells possess unique and specialized mechanisms to maintain genomic stability. To this end we are developing both live and fixed cell imaging techniques to study mitotic progression. We are also collaborating with Andrea Ballabeni, post-doctoral fellow in Marc Kirschener’s lab, to perform biomolecular analysis of the pluripotent stem cell cycle.
Articles in PubMed