Faculty & Research
- Contact Information
- Contact Christina Dann by ctdann [at] indiana [dot] edu
- By telephone: 812-855-0821
- By fax: 812-855-6082
- Myers 216B
- Research Areas
- Developmental Mechanisms and Regulation in Eukaryotic Systems
- Eukaryotic Cell Biology, Cytoskeleton and Signaling
Postdoctoral Fellow, UT Southwestern Medical Center, 2002-2008
Ph.D., Johns Hopkins University, 2001
B.S., College of William and Mary, 1996
Lalor Foundation Research Fellow, 2005
National Institutes of Health R21 award, 2010
The life-long production of specialized adult cells with short life spans, such as skin, blood or sperm, depends upon the maintenance of a pool of progenitor cells called stem cells. Stem cells are defined by their ability to proliferate in a way that leads to the production of differentiated cells while continuing to maintain a pool of stem cells (self renewal). During normal development the stem cells balance self renewal and differentiation. Additionally, the stem cells have the capacity for increased cellular expansion following tissue damage. My lab’s research is focused on spermatogonial stem cells (SSCs), which provide the foundation for the production of sperm. We have two interwoven long-term goals. One goal is to elucidate molecular mechanisms regulating SSC fate. Another equally important goal is to develop technologies that will contribute to the realization of SSC-based therapies.
SSCs are a very rare cell type residing in the complex architecture of the seminiferous tubules within the testis. Therefore, we have begun our studies on the regulation of SSC fate by using an in vitro culture system. Our lab is using reverse genetic approaches such as gene knockdown (RNAi) and overexpression to manipulate the expression levels of various factors, such as OCT4, and microscopy and molecular analyses to assess the effect of the manipulations on cell fate.
Another area of our research is focused on SSC-based therapies. Thousands of diseases are caused by a change in a single gene. Gene therapy is the process of treating such diseases by providing a corrected form of the gene, ideally in the stem cells that are progenitors to the diseased cells. We are developing tools for correcting mutant genes in SSCs using nucleases engineered to create a gene-specific double strand break, thereby stimulating homologous recombination with a piece of repair DNA. Then the corrected cells will be transplanted into a sterile host mouse to test the function of the genetically manipulated stem cells in restoring fertility. Applications of this approach include: generating transgenic animals, correcting gene defects in germ cells followed by transplantation to assure that progeny would not carry the mutant gene, and using gene corrected SSCs to generate pluripotent ES-like cells for subsequent autologous cell based therapies. Our pursuit of technology for efficient gene correction in SSCs represents an important first step toward the ambitious goal of SSC-based gene therapy.
- Heim, C., Minniear, K., Dann, C.T. (2011) Imatinib mesylate has deleterious effects on differentiated spermatogona while sparing spermatognial stem cell self renewal. Reproductive Toxicology. 31, 454-463.
- Richardson T.E., Chapman K.M., Dann C.T., Hammer R.E. and Hamra F.K. (2009) Sterile testis complementation with spermatogonial lines restores fertility to DAZL-deficient rats and maximizes donor germline transmission. PLoS ONE, Jul 21;4(7):e6308.
- Dann, C.T., Alvarado, A., Molyneux, L., Denard, B.S., Garbers, D.L., Porteus, M.H. (2008) Spermatogonial Stem Cell Function Requires OCT4, a Factor Down-regulated During Retinoic Acid Induced Differentiation in vitro. Stem Cells. Nov;26(11):2928-37.
- Dann, C.T. and Garbers. D.L. (2008) Production of Knockdown Rats by Lentiviral Transduction of Embryos with Short Hairpin RNA Transgenes. In Hou, S. X. and Singh S. R. (Eds.), Methods in Molecular Biology: Germline stem cells (pp 193-209). Totowa, NJ: Humana Press.
- Dann, C.T. (2007) New Technology for an Old Favorite: Lentiviral Transgenesis and RNAi in Rats. Transgenic Research. 16, 571-580.
- Dann, C.T., Alvarado, A., Hammer, R., Garbers. D. (2006) Heritable and Stable Gene Knockdown in Rats. PNAS. 103, 11246 -11251. [PMC1544073]
- Tenenhaus, C., Subramaniam, K., Dunn, M., Seydoux, G. (2001) PIE-1 is a Bifunctional Protein that Regulates Maternal and Zygotic Gene Expression in the Embryonic Germline of C. elegans. Genes and Development. 15, 1031-1040. [PMC312670]
- Tenenhaus, C., Schubert, C., Seydoux, G. (1998) Genetic Requirements for PIE-1 Localization and Inhibition of Gene Expression in the Embryonic Germ Lineage of C. elegans. Developmental Biology. 200, 212-224.