Prof. Karim Nayernia
Prof of Stem Cell Biology
- Address: Institute of Human Genetics
Newcastle University
International Centre for Life
Central Parkway
Newcastle upon Tyne
NE1 3BZ
UK
Research Interests
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
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. This approach provide a powerful tool for study of male infertility.
2. Potential of spermatogonial stem cells to differentiate to somatic stem cells
Recently, we have isolated spermatogonial stem cells from adult male mice. These cells are physiologically responsible for the continuous production of sperm 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.
3. The germline origin of cancer stem cells
With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. We identify germ cell markers with expression in breast cancer which might lead to molecular targeting of breast cancer stem cells and improving the efficacy of the current anti-cancer strategies with the aim to sensitize tumors toward conventional therapies and effectively abrogate tumorigenesis.
4. Establishment of stem cell based alternative strategies for reproductive toxicology
Exposure of mammalian germ cells to environmental or therapeutic agents may cause DNA damage or changes in gene expression. These changes can result in fertility problems and may affect the offspring.The aim is to establish an in vitro spermatogenesis system and to investigate the effects of a variety of reproductive toxicants, like environmental estrogenic compounds and anti-cancer drugs, on morphology, proliferation, differentiation, apoptosis, gene expression on germ cell at distinct premeiotic, meiotic and postmeiotic stages, and find the most sensitive assays to develop new test-strategies.
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.
Selected Publications
- Nayernia K, Nolte J, Michelmann HW, Lee JH, Rathsack K, Drusenheimer N, Dev A, Wulf G, Ehrmann IE, Elliott DJ, Okpanyi V, Zechner U, Haaf T, Meinhardt A, Engel W. In Vitro-Differentiated Embryonic Stem Cells Give Rise to Male Gametes that Can Generate Offspring Mice. Developmental Cell 2006, 11(1), 125-132.
- 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.
- 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.
- 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.
- Nayernia K, Li M, Jaroszynski L, Khusainov R, Wulf G, Schwandt I, Korabiowska M, Michelmann HW, Meinhardt A, Engel W. Stem cell based therapeutical approach of male infertility by teratocarcinoma derived germ cells. Hum Mol Genet 2004, 13, 1451-1460.
- Nayernia K, Vauti F, Meinhardt A, Cadenas C, Schweyer S, Meyer BI, Schwandt I, Chowdhury K, Engel W, Arnold HH. Inactivation of a Testis-specific Lis1 Transcript in Mice Prevents Spermatid Differentiation and Causes Male Infertility. The Journal of Biological Chemistry 2003, 278(48), 48377-48385.
Previous Positions
2003 Associate Professor in Human Molecular Genetics, University of Goettingen
1997-2006 Director of molecular genetic diagnostics (HHT, Factor V, Yq11)
1996-2003 Group leader, Molecular Genetics of germ cell differentiation
1996-1999 Head of special DFG research group : Testicular germ cell tumors
1993-1996 Research Associate, Institute of Human Genetics, University of Goettingen
