Newcastle University

Prof. Karim Nayernia
Prof of Stem Cell Biology

• Email: karim.nayernia@ncl.ac.uk
• Telephone: +44 (0)191 241 8643
• Address: Chair of Stem Cell Biology
  Institute of Human Genetics
  University of Newcastle upon Tyne
  International Centre for Life
  Central Parkway
  Newcastle upon Tyne
  NE1 3BZ

In its most general sense, our research programme seeks to elucidate molecular mechanisms underlying development and differentiation of germline and cancer stem cells. Within this framework, we are exploring four general issues:
1. Potential of embryonic and adult stem cells to differentiate to male germ cells and establishment of in vitro spermatogenesis system

2. Potential of spermatogonial stem cells to differentiate to somatic stem cells.
3. The germline origin of cancer stem cells
4. Establishment of stem cell based alternative strategies for reproductive toxicology

Research Interests

From stem cells to germ cells and back

In its most general sense, our research programme seeks to elucidate molecular mechanisms underlying development and differentiation of germline stem cells.

Within this framework, we are exploring three general issues:

1. Potential of embryonic and adult stem to differentiate to male germ cells
2. Potential of spermatogonial stem cells to differentiate to somatic stem cells.
3. Functional analysis of genes involved in germline stem cell proliferation and differentiation.

Recently, we have isolated spermatogonial stem cells from adult male mice. These cells are physiologically responsible for the continuous production of sperm cells. We then showed that these cells, when cultured in a test tube, can be brought into a condition that mimics that of embryonic stem cells. The cells form a cell mass (embryoid body), which can differentiate into various if not all cell types of the organism. These results may help to avoid the ethical and immunological problems that arise when embryonic stem cells are used in medical research. We have laid the basis for a future treatment of severe illnesses like cardiac insufficiency, Parkinson’s, Alzheimer and muscle dystrophy with the help of a body’s own stem cells.

Using another approach, we developed a strategy for the establishment of spermatogonial stem cell lines from embryonic stem cells (ES). These cells are able to undergo meiosis, generate haploid male gametes in vitro and are functional, as shown by fertilization after intra-cytoplasmic injection into mouse oocytes. Molecular and cellular mechanisms underlying differentiation of ES to functional gametes should be elucidated in future research.

In third approach, we show that bone marrow stem cells are able to trans-differentiate into male germ cells. BMS cell-derived germ cells expressed the known molecular markers of primordial germ cells. Our ability to derive male germ cells from bone marrow stem cells provides novel aspects of germ cell development.

In exploring these issues we use a variety of research tools and experimental systems, including generation of transgenic and knockout mice, in vitro gametogenesis system, in vitro differentiation systems and laboratory work employing cytological, molecular, cellular and embryological techniques.

Key publications

Guan K, Nayernia K, Maier LS, Wagner S, Dressel R, Lee JH, et al. (2006) Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 440:1199-1203

Lee JH, Schutte D, Wulf G, Fuzesi L, Radzun HJ, Schweyer S, et al. (2006) Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Hum Mol Genet 15:201-211

Nayernia K, Nolte J, Michelmann HW, Lee JH, Rathsack K, Drusenheimer N, et al. (2006) In vitro-differentiated embryonic stem cells give rise to male gametes that can generate offspring mice. Dev Cell 11:125-132

Co-workers

Hamid Reza Soleimanpour Lichaei, PhD
European Commission Research Associate
Christian Mueller
Newcastle University Technician

Selected Publications

• Guan K, Nayernia K, Maier LS, Wagner S, Wolf F, Li M, Engel W, Hasenfuss GP. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 2006, 440(7088), 1199-1203.
• Nayernia K, Lee J.H, Drusenheimer N, Nolte J, Wulf G, Schwandt I, Ralf D, Müller C.H, Gromoll J, Engel W. Derivation of germ cells from bone marrow stem cells. Lab Invest 2006, 86, 654-663.
• Lee J.H, Engel W, Nayernia K. Stem Cell Protein Piwil2 Modulates Expression of Murine Spermatogonial Stem Cell Specific Genes. Mol Reprod Dev 2006, 73(2), 173-179.
• Lee JH, Schütte D, Wulf D, Füzesi L, Radzun HJ, Schweyer S, Engel W, Nayernia K. Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Human Molecular Genetics 2006, 15(2), 201-211.

Postgraduate Teaching

MRes Stem Cells & Regenerative Mediciene
6 PhD Students