Dr. Catherine Kirn-Safran

Research Assistant Professor

Contact

Kirn-Safran

Office: 310 Wolf Hall
Lab: 332 Wolf Hall

Mailing address:
Dept. of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

Phone: (302) 831-3249
Pager: (302) 433-1146
Fax: (302) 831-2281
E-mail: ckirn@udel.edu

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Education

B.S., M.S., Ph.D.: University Louis Pasteur, France
Postdoctoral: University of Texas, M.D. Anderson Cancer Center

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Research Interests

Dr. Kirn-Safran is best known for her work on the study of the terminal differentiation of progenitor cells into cells producing an organized mineralized extracellular matrix (ECM) during murine embryonic development. This area of research includes the study of the mechanisms of cartilage (chondrogenesis), bone (osteogenesis), and tooth (odontogenesis) development.

During the past years, Dr. Kirn-Safran has worked to develop a knock-out mouse model that disrupts the expression of a ribosomal protein of the ribosome large subunit, RPL29, which is abundant in developing bone. The phenotypic characterization of these mutant mice reported global growth deficiencies evident both prior to and after birth (Kirn-Safran et al., 2007). Interestingly, low birth weight was accompanied by a short stature phenotype. Reduced rates in proliferation and protein synthesis are believed to be the cause of this phenotype. These results are consistent with data reported in yeast, where RPL29 contributes to proper association between the two ribosomal subunits and, consequently, plays a role in protein translational efficiency. Dr. Kirn-Safran is currently collaborating with Dr. Dinman (Univ. of Maryland, College Park, MD), an expert in translational fidelity and ribosome structure in yeast, to understand the function of RPL29 in ribosome assembly and possibly rRNA structure using both yeast and mouse RPL29-deficient ribosomes. These studies are anticipated to serve as a basis to bridge our current understanding of ribosome structure/function relationships from the simple eukaryote to a complex mammalian system.

Dr. Kirn-Safran's ongoing research focuses on establishing how ECM protein production/secretion is altered in the RPL29-deficient mouse model. She is using an osteoinductible primary mouse embryonic cell culture system to determine how defects in ribosomal integrity can impact the steady-state expression levels of specific bone ECM proteins in RPL29-deficient mice. The goal of her current research is to study the consequences of reduced ECM protein production on bone/cartilage repair and aging. Recently, her group has been working on developing a mouse model of knee osteoarthritis.

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Current Projects

• NIH COBRE, Perlecan, Heparanase, and HIP/RPL29 in Cartilage Growth and Healing (Co-PI with Dr. Mary C. Farach-Carson)

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Research Group

• David Tuke, B.A. - Research Assistant (B.A., University of Delaware). Growth factor-induced repair of knee osteoarthritis in mice.
• Laura Sloofman - Undergraduate Student. Study of the effects of RPL29 knock-out on bone structure and rigidity.

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Selected Publications

Oristian D.S., Sloofman L.G., Zhou X., Wang L., Farach-Carson M.C., and Kirn-Safran C.B. Ribosomal protein L29/HIP deficiency delays osteogenesis and increases fragility of adult bone in mice. Submitted.

Brown A.J., Alicknavitch M., D'Souza S.S., Daikoku T., Kirn-Safran C., Marchetti D., Carson D.D., and Farach-Carson M.C. Heparanase expression and activity influences chondrogenic and osteogenic processes during endochondral bone formation. In press.

Kirn-Safran C.B., D'Souza S.S., and Carson D.D. Heparan sulfate proteoglycans and their binding proteins in embryo implantation and placentation. Seminars in Cell and Developmental Biology, 2008, 19: 187-193.

Kirn-Safran C.B., Oristian D.S., Focht R.J., Parker S.G., Vivian J.L., and Carson D.D. Global growth deficiencies in mice lacking the ribosomal protein HIP/RPL29. Developmental Dynamics, 2007, 236: 447-460.

Kirn-Safran C.B., Gomes R.R., Brown A.J., and Carson D.D. Heparan sulfate proteoglycans: Coordinators of multiple signaling pathways during chondrogenesis. Birth Defects Research (Part C), 2004, 72: 69-88.

Miller S.A., Brown A.J., Farach-Carson M.C., Kirn-Safran C.B. HiP/RPL29 down-regulation accompanies terminal chondrocyte differentiation. Differentiation, 2003, 71: 322-336.

Kirn-Safran C.B., Julian J., Fongemie J.E., Hoke D.E., Czymmek K.J., and Carson D.D. Changes in the distribution of heparin/heparan sulfate interacting protein/ribosomal protein L29 (HiP/RPL29) during in vivo and in vitro mouse mammary epithelial cell expression and differentiation. Developmental Dynamics, 2002, 223: 70-84.

Kirn-Safran C.B., Sandeep D., Martin-Deleon P.A., and Carson D.D. Identification of a single copy gene encoding for murine HiP/RPL29 in the presence of multiple pseudogenes: structure, expression, and mapping. Genomics, 2000, 68: 210-219.

Kirn-Safran C.B. and Carson D.D. Dynamics of uterine glycoconjugate expression and function. Seminar in Reproductive Endocrinology, 1999, 17: 217-227.

Hoke D.E., Regisford G.C., Julian J., Amin A., Bègue-Kirn C. and Carson D.D. Murine HiP/L29 is a heparin-binding protein with a restricted pattern of expression in adult tissues. Journal of Biological Chemistry, 1998, 273: 25148-25157.

Bègue-Kirn C., Krebsbach P.H., Bartlett J.D. and Butler W.T. Dentin sialoprotein, dentin phosphoprotein, enamelysin and ameloblastin: tooth-specific proteins that are distinctively expressed during murine dental differentiation. European Journal of Oral Science, 1998, 106: 963-970.

Sun Z.L., Fang D.N., Wu X.Y., Ritchie H.H., Bègue-Kirn C., Wahata J.C., Hanks C.T. and Butler W.T. Expression of dentin sialoprotein (DSP), dentin phosphoprotein (DPP) and other molecular determinants by MDPC-23. Connective Tissue Research 1998, 37: 251-261.

Heikinheimo K., Bègue-Kirn C., Ritvos O., Tuuri T. and Ruch J.V. Activin and bone morphogenetic protein (BMP) signalling during tooth development, European Journal of Oral Science, 1998, 106 Suppl 1: 167-173.

Bègue-Kirn C., Ruch J.V., Ridall A.L. and Butler W.T. Comparative analysis of mouse DSP and DPP expression in odontoblasts and experimentally induced odontoblast-like cells, European Journal of Oral Science, 1998, 106 Suppl 1: 254-259.

Heikinheimo K., Bègue-Kirn C., Ritvos O., Tuuri T. and Ruch, J.V. The activin-binding protein follistatin is expressed in developing murine molar and induces odontoblast-like cell differentiation in vitro. Journal of Dental Research, 1997, 76: 1625-1636.

Smith A.J., Tobias R.S., Cassidy N., Bègue-Kirn C., Ruch J.V. and Lesot H. Influence of substrate nature and immobilisation of implanted dentin matrix components during induction of reparative dentinogenesis. Connective Tissue Research, 1995, 32: 291-296.

Smith A.J., Cassidy N., Perry H., Bègue-Kirn C., Ruch J.V. and Lesot H. Reactionary dentinogenesis. International Journal of Developmental Biology, 1995, 39: 273-280.

Bègue-Kirn C., Smith A.J., Loriot M., Kupferle C., Ruch J.V., and Lesot H. Comparative analysis of TGF beta s, BMPs, IGF1, msxs, fibronectin, osteonectin and bone sialoprotein gene expression during normal and in vitro-induced odontoblast differentiation. International Journal of Developmental Biology, 1994, 38: 405-20.

Lesot H., Bègue-Kirn C., Kubler M.D., Meyer J.M., Smith A.J., Cassady N., and Ruch J.V. Experimental induction of odontoblast differentiation and stimulation during reparative processes. Cells and Materials, 1993, 3: 201-217.

Bègue-Kirn C., Smith A.J., Ruch J.V., Wozney J.M., Purchio A., Hartmann D., and Lesot H. Effects of dentin proteins, transforming growth factor βl (TGFβl) and bone morphogenetic protein 2 (BMP2) on the differentiation of odontoblast in vitro. International Journal of Developmental Biology, 1992, 36: 491-503.

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