Description of Research Expertise

Research Interests
- biology of male germ line stem cells
- sperm physiology
- transgenesis

Key words: male, germ cells, stem cells, transgenesis, testis, spermatogenesis.

Description of Research
The long-term objective of my research program is to establish a system to study the biology of male germ line stem cells in non-rodent mammalian species. Recently, we succeeded in establishing the technique or germ cell transplantation in pigs and goats. This system will serve as a bioassay for stem cell potential of a given germ cell population, and will allow the manipulation of different aspects of spermatogenesis. Furthermore, it will lay the foundation for manipulation of the male germ line as an alternate approach to generate germ line transgenic animals. Present strategies to generate transgenic domestic animals are limited to pronuclear microinjection or nuclear transfer technology. Unfortunately, both these approaches are hampered by low efficiency due to excessive pregnancy wastage and perinatal losses, making the technology expensive and requiring large numbers of animals. Therefore, there is keen interest in the industry to find alternate, potentially more efficient ways of generating transgenic animals in species where embryonic stem cell technology is not available. Transgenesis through modification of the male germ line is one such promising approach. In addition, germ cell transplantation will serve to preserve valuable genetic material of animals and can be clinically applicable to restore fertility in cancer patients undergoing cytotoxic therapy.

Experimentation in non-rodent target species is inherently difficult, time consuming and expensive. In order to have a model system for the study and manipulation of spermatogenesis that is applicable to a variety of mammalian species including primates, we have recently developed the technique of testis tissue xenografting into mouse hosts. This approach allowed for the first time complete spermatogenesis and production of functional sperm from neonatal testis tissue obtained from newborn pigs and goats transplanted into a mouse. This strategy holds great potential not only as a basic science tool for the study of spermatogenesis in different species, but also for preservation of male genetics from immature individuals like endangered animals, valuable laboratory strains or farm animals, and potentially even human childhood cancer patients. We observed that xenografting of neonatal testis tissue can accelerate sperm production. Accelerating sperm production could become a tool to shorten the generation interval on the male side, equivalent to using oocytes from immature calves for in vitro fertilization. Application of testis tissue xenografting to primates provides a system to study the effect of toxins and potential male contraceptive agents on primate testis function in the mouse, eliminating the need for experimentation in the target species. Finally, we investigate the application of testis tissue xenografting for animal conservation.

Germ cell transplantation and testis tissue xenografting are novel, exiting research areas with tremendous potential both for basic research into male germ line stem cell biology and spermatogenesis, as well as applications for animal transgenesis and genetic preservation.

Rotation Projects for 2006-2007
Culture of Germline Stem Cells from Porcine Testis, Xenografting of adult primate testis, Genetic manipulation of procine germ cells.

Lab personnel:
Dr. Hannah Galantino-Homer, Lecturer
Dr. Wenxian Zeng, research Specialist
Dr. Rahul Rathi, Postdoctoral Fellow
Dr. Jinping Luo, Postdoctoral Fellow
Fangping Chen, Research Assistant
Susan Megee, Research Specialist
Mark Modelski, Research Assistant