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Germ Cell Biology and Reproductive Medicine/ Stem Cell & Regenerative Medicine


The Department of Biomedical Sciences has maintained a longstanding interest in germ cell and stem cell biology, reproductive biology and regenerative medicine.  Since the 1960s, brinstercover Science 2002our faculty has conducted groundbreaking work, including that of Dr. Ralph Brinster, who developed some of the earliest techniques for manipulating mouse embryos and was one of the first to generate transgenic mice by injecting genes into the pronucleus of a zygote, and Dr. Hans Scholer, who made landmark discoveries concerning the molecular basis of pluripotency – the ability of a stem cell to give rise to all cell types.  Today, work in the section for Germ Cell Biology and Reproductive Medicine/Stem Cell & Regenerative Medicine has expanded to also include adult stem cell biology.  Our faculty members are engaged in understanding how stem cells govern adult tissue and its responses to injury, illustrating the structure and function of the stem cell niche, and identifying the factors that affect the role of the stem cell in tumorigenesis.  Additionally, the Department of Animal Biology houses the Penn Vet Center for Animal Transgenesis and Germ Cell Research, which enables the genetic manipulation and generation of transgenic, knockout and knockin animals for disease modeling.


Faculty


  • Dr. Ralph Brinster
    • Our laboratory focuses on the biology of the spermatogonial stem cell (SSC), which is responsible for the continuity of spermatogenesis in the adult male. A spermatogonial cell transplantation technique has been developed that provides a functional assay of stem cell activity, thereby enabling for the first time an analysis of this unique and valuable stem cell population. Using the transplantation assay the surface antigenic profile of the SSC has been established for several species, and this information allows highly enriched populations of stem cells to be obtained. These enriched SSCs from mouse and rat can now be cultured, and their number increased for long periods. Techniques to extend the culture system to farm animals and primates are under investigation. Additionally, genes are being introduced into the SSC as a technique to modify the germline of animals. Development of culture and gene modification methods for rodent SSCs will lay the foundation for similar approaches in larger animals, particularly farm animals. The culture and enrichment strategies also are being used to study gene activity in stem cells and differentiating daughter cells arising from the stem cells. Using similar methods, signaling pathways active in the fate decision determining stem cell self-renewal or differentiation are under investigation. Since the SSC is the only adult stem cell for which there exists a long-term in vitro culture system and a quantitative functional transplantation assay, it provides a powerful model to understand stem cell function in all adult stem cell systems. In addition, the SSC is the only stem cell in the adult that continually replicates and transmits genes to the next generation. Perhaps most important, it is the vehicle for species continuity and evolutionary adaptation.

       

  • Dr. Olena Jacenko
    • Dr. Olena JacenkoOur lab maintains that extracellular matrix components help establish temporal-spatial niches throughout skeletal and hematopoietic development, homeostasis and aging. In our research we propose that endochondral skeletogenesis, which relies on a transient cartilage template, establishes the lymphopoietic niche that is comprised of a subset of cartilage and bone cells and their unique matrix products. Some of our major research effort involves use of mouse models to define the prerequisite skeletal-hematopoietic interactions for niche establishment and function.
  • Dr. Chris Lengner
    • Our lab is broadly interested in the mechanisms by which both Dr. Christopher Lengnersomatic and embryonic stem cells acquire and maintain developmental potency. We are also exploring how deregulation of these mechanisms can contribute to oncogenic transformation and tumorigenesis, and how we can learn to manipulate these mechanisms for application in disease modeling and regenerative medicine. In particular, we are focused on understanding how the Musashi (Msi) family of RNA binding proteins function to control normal stem cell activity in the intestinal epithelium and how their aberrant activation drives colorectal cancers.
  • Dr. Ellen Puré
    • Dr. Ellen Puré, Penn VetAt least some tumor types including hematopoietic tumors and certain solid tumors such as breast cancer, are reportedly sustained by so-called cancer initiating cells that share many properties with stem cells, and are therefore referred to in some instances as cancer stem cells. Maintenance of normal stem cells is supported by specialized niches and by analogy, specialized niches have been speculated to play critical roles in maintaining cancer initiating cells. A major focus of the studies in our lab is on the role of stroma in regulating tumor cell behavior. Current studies are focused on the role of tumor associated stromal cells and matrix remodeling in defining the morphologic heterogeneity and tumor cell fate in distinct regions of the tumor microenvironment and in the pre-metastatic niche that may be required for the development of metastatic disease. These studies will address the role of stroma in maintaining cancer initiating cells or cancer stem cells and will be extended to define the role of stroma in maintaining normal stem cells.
  • Dr. Jeremy Wang
    • Our group focuses on the study of meiosis in mice and humans. Meiosis, a cell division unique to germ cells, allows the reciprocal exchange of genetic material between paternal and maternal genomes. Meiosis generates the genetic diversity necessary for evolution of species. Abnormality in meiosis is a leading cause of birth defects and infertility. Our research interests include molecular genetics of chromosomal synapsis, DNA double-strand break repair, homologous recombination, genetic causes of male infertility in humans, and piRNA biogenesis. Functional characterization of a number of new genes in our laboratory has uncovered novel regulatory mechanisms underlying key biological processes unique to germ cells. On one hand, our studies provide molecular insights into the development of germ cells in mice. On the other hand, these mouse studies have important implications for understanding the genetic causes of male infertility in humans and developing novel male contraceptives.