K. John McLaughlin, PhD
Assistant Professor, Dept of Animal Biology, Center for Animal Transgenesis and Germ Cell Research

Developmental Biology Program

Address

The School of Vet. Med., Univ. of Penn
New Bolton Center
382 West Street Road
Kennett Square, PA 19348

Office tel.: 610-925-6288
Lab tel.: 610-925-6271
Fax: 610-925-8121
E-mail: kjmclaug@vet.upenn.edu

Link(s)

McLaughlin at Penn Vet Medicine

Penn Center for Developmental Biology

Center for Research on Reproductive & Women's Health

Education

University of Adelaide: BS (Science), 1987.

University of Adelaide: PhD (Reproductive Biology/Cloning), 1992.

Research Interests

• genomic imprinting, somatic cell reprogramming, embryonic stem cells

Search PubMed for articles

Description of Research

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. In mammals, genomic imprinting limits the development of uniparental embryos such as parthenogenetic embryos. One research direction within the field is to determine the mechanism(s) by which imprinted genes are expressed or silenced depending on parental origin.

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.

This figure shows how uniparental embryos are produced by pronuclear transplantation such that the resulting embryos have either entirely paternally inherited (above, AG) or entirely maternally inherited genomes (below, GG and PG).

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.

Current and future projects include:

• Functional evaluation of engrafted uniparental adult hematopoietic cells
• Transplantation of uniparental germ cells
• Proliferation and differentiation of uniparental neurospheres
• In vitro differentiation of androgenetic embryonic stem cells (neural, cardiac, pancreatic)
• Genomic imprinting (methylation and expression) in adult engrafted uniparental cells
  

Recent Publications

Eckardt, S., Leu, N. A., Bradley, H.L. , Kato, H., Bunting, K.D. and McLaughlin, K. J. Hematopoietic reconstitution with androgenetic and gynogenetic stem cells. Genes Dev, Feb 15, 2007, in press.

Eckardt, S., Leu, N.A., Kurosaka, S., McLaughlin, K.J., Differential reprogramming of somatic cell nuclei after transfer into mouse cleavage stage blastomeres. Reproduction 2005. May;129(5): 547-56.

Eckardt, S. and McLaughlin, K.J., Interpretation of reprogramming to predict success in somatic cell cloning. Animal Reproduction Science 2004. 82-83:97-108, 2004.

Kurosaka, S., Eckardt, S., McLaughlin K.J. Pluripotent lineage definition in bovine embryos by Oct4 transcript localization. Biol Reprod, 2004. Nov;71(5):1578-82

Boiani, M., Eckardt, S., Leu, N.A., Schöler, H.R., McLaughlin, K.J. (2003). Aggregation of mouse clone-clone embryos rescues pluripotency. EMBO Journal 2003