Our knowledge of the human embryonic stem cell 3D microenvironment in culture remains extremely basic and is a prerequisite for robust biomedical therapies that currently require large cell numbers to be transplanted. Similar constraints also apply to induced pluripotent stem cells as well as additional concerns with genomic alterations that promote tumorigenesis upon transplantation or accelerate ageing. Minimal information currently exists on homogeneity or heterogeneity of pluripotent stem cell populations, whether subtle dedifferentiation and differentiation are occurring and how intercellular cues generate intracellular changes.
Professor Paluh is investigating Cell Cycle signaling pathways, DNA damage and internal and external spatiotemporal changes that occur in pluripotent stem cell populations during transitions from quiescence to self-renewal and upon differentiation. Differentiation along neuronal lineages is the current focus. Investigation is underway to develop better biomarkers of stem cell homogeneity, DNA damage and ECM signaling events occurring during these cellular transitions. In addition the development of better in vitro 4D platforms that direct and are responsive to changing stem cell needs for tissue architecture is also being investigated through collaborative efforts with Materials Science and Engineering Departments at RPI. Professor Paluh's initial training in human embryonic stem cells and neuronal stem cells is via WiCell, NIH and CHOC.
Paluh JL. Sentinels of DNA integrity in stem cells: safeguarding future generations of cells. Cell Cycle. 2008 Sep 15;7(18):2779. Epub 2008 Sep 15. No abstract available.
Rodriguez AS, Batac J, Killilea AN, Filopei J, Simeonov DR, Lin I, Paluh JL. Protein complexes at the microtubule organizing center regulate bipolar spindle assembly.
Cell Cycle. 2008 May 1;7(9):1246-53. Epub 2008 Feb 22.
Mayer C, Filopei J, Batac J, Alford L, Paluh JL. An extended anaphase signaling pathway for Mad2p includes microtubule organizing center proteins and multiple motor-dependent transitions. Cell Cycle. 2006 Jul;5(13):1456-63. Epub 2006 Jul 1.