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MCLAUGHLIN LABORATORY
Genomic imprinting refers to the phenomenon that, in somatic cells, certain genes are preferentially expressed from one parental allele, such that maternally and paternally inherited genetic information is expressed unequally.
We are interested in the consequences when imprinted gene expression patterns are disrupted, as this will lead to understanding as to why this unique gene control mechanism exists. We are using mouse models in which expression of imprinted genes is disturbed. One model is uniparental development including parthenogenesis and the paternal genome derived equivalent, androgenesis.
We are currently integrating our study of uniparental cells within the concept of generating autologous embryonic stem cells. Parthenogenetic embryos have been discussed as a source of patient matching embryonic stem cells. To validate this concept we are investigating the capacity of parthenogenetic stem cell derived cells (fetal and grown under certain conditions in vitro/in tissue culture), to replace adult bone marrow/hematopoiesis. Additionally we are also testing androgenetic embryonic stem cells, to increase the potential patient pool for a therapeutic approach based on uniparental cells. Biologically, this model can be used as a system to study the relevance of genomic imprinting in adult tissues.
An experimental strategy to investigate the ability of uniparental cells to engraft and differentiate in adults. Uniparental ES cells are injected into normal mouse blastocysts to generate composite fetuses (chimeras). Fetal liver cells from chimeras are then transplanted into lethally irradiated adults to reconstitute hematopoiesis.
Investigating both androgenetic and gynogenetic/parthenogenetic cells, we are differentiating (in vivo and in vitro) and transplanting uniparental cells to various tissues to determine the broader utility for tissue replacement therapy.
Web Site:: http://transgenicmousecore.nchresearch.org/
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| Education |
| 1992 |
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PhD |
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Obstetrics and Gynecology |
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University of Adelaide, Australia |
| 1987 |
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BSc, Honors |
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Reproductive Physiology |
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University of Adelaide, Australia |
| 1986 |
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BSc |
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Biology |
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University of Adelaide, Australia |
| Professional Experience |
| 2009- PRES |
Associate Professor, Department of Pediatrics,
The Ohio State University College of Medicine,
Columbus, Ohio |
| 2009- PRES |
Director, Transgenic and Embryonic Stem Cell Core, Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio |
| 1999- 2008 |
Assistant Professor, University of Pennsylvania, Department of Animal Biology, School of Veterinary Medicine |
| 1999- 2008 |
Director, Myrin Rodent Barrier Facility, Center for Animal Transgenesis and Germ Cell Research, School of Veterinary Medicine, University of Pennsylvania |
| 1998- 1999 |
Lecturer C, University of Pennsylvania, Department of Animal Biology, School of Veterinary Medicine |
| 1998- 1998 |
Visiting Scientist, University of Western Ontario, Canada |
| 1994- 1998 |
Scientist, Max Planck Institute for Immunobiology, Freiburg,
Germany |
| 1992- 1994 |
Postdoctoral Scientist, Beckman Research Institute, City of Hope Duarte, Los Angeles, USA |
| 1991- 1992 |
Visiting Postgraduate Research Scientist University of California, San Francisco, USA |
| Selected Publications |
| Balbach, S., Esteves, T., Brink, T., Gentile, L., McLaughlin, K.J., Adjaye, J., and Boiani, M. (2010). Governing cell lineage formation in cloned mouse embryos. Dev Biol (in press). |
| Liu J, Carc=valho LP, Bhattachariya S, Carbone CJ, Kumar KG, Leu NA, Yau PM, Donald RG, Weiss MJ, Baker DP, McLaughlin KJ, Fuchs SY. "Mammalian casein kinase 1alpha and its leishmanial ortholog regulate stability of IFNAR1 and Type I interferon signaling". Mol Cell Biol. 2009 Oct 5 (Epub) PubMed ID: 19805514 |
| Choi YH, Harding HD, Hartman DL, Obermiller AD, Kurosaka S, McLaughlin KJ, Hinrichs K. "The uterine environment modulates trophectodermal POU5F1 levels in equine blastocysts". Reproduction. 2009 Sep;138 (3): 589-99 PubMed ID: 19525365 |
| De Sousa PA, Gardner J, Sneddon S, Pells S, Tye BJ, Dand P, Collins DM, Stewart K, Shaw L, Przborski S, Cooke M, McLaughlin KJ, Kimber SJ, Lieberman BA, Wilmut I, Brison DR. "Clinically failed eggs as a source of normal human embryo stem cells". Stemm Cells Res. 2009 Feb 6 (epub) PubMed ID: 19393594 |
| Pan J, Eckardt S, Leu NA, Buffone MG, Zhou J, Gerton GL, McLaughlin KJ, Wang PJ. "Inactivation of Nxf2 causes defects in male meiosis and age-dependent depletion of spermatogonia". Dev Biol. 2009 Jun 1;330(1):167-74 PubMed ID: 19345203 |
| Rai R, Wong CC, Xu T, Leu NA, Dong DW, Guo C, McLaughlin KJ, Yaes JR 3rd, Kashina A. "Arginyltransferase regulates alpha cardia actin function, myofibril formation and contractility during heart development". Development. 2008 Dec;135(23):3881-9 PubMed ID: 18948421 |
| Eckardt S, McLaughlin KJ. "Transplation of chimeric fetal liver to study hematopoiesis". Methods Mol Biol. 2008 430:195-211. PubMed ID: 18370301 |
| Dinger TC, Eckardt S, Choi SW, Camarero G, Kurosaka S, Hornich V, McLaughlin KJ, Muller AM. "Androgenetic embryonic stem cells form neural progenitor cells in vivo and in vitro". Stem Cells. 2008 Jun;26(6):1474-83 PubMed ID: 18369101 |
| Yang F, Gell K, van der Heijden GW, Eckardt S, Leu NA, Page DC, Benavente R, Her C, Hoog C, McLaughlin KJ, Wang PJ. "Meiotic failure in male mice lacking an x-linked factor". Genes Dev. 2008 Mar 1;22(5):682-91 PubMed ID: 18316482 |
| Yang F, Eckardt S, Leu NA, McLaughlin KJ, Wang PJ. "Mouse TEX15 is essential for DNA double-strand break repair and chromosomal synapsis during male meiosis". J Cell Biol. 2008 Feb 25;180(4):673-9. PubMed ID: 18283110 |
| Eckardt S, Dinger TC, Kurosaka S, Leu NA, Muller AM, McLaughlin KJ. "In vivo and vitro differentiation of uniparental embryonic stem cells into hematopoietic and neural cell types". Organogenesis. 2008 Jan;4(1):33-41 PubMed ID: 19279713 |
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