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Catherine B. Kirn-Safran, Ph.D.
Introductory Biology II (BISC208)
Teaching Experience (BISC422)
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.
Dr. Kirn-Safran's group has been working on identifying novel strategies to slow osteoarthritis progression. One approach consists of using heparan sulfate-bearing biomaterials coupled to hyaluronan microgels for prolonged delivery of chondrogenic factors. This work is conducted in collaboration with Dr. Xinqiao Jia (UD, Department of Materials Science and Engineering). The therapeutic potential of these complexes was tested in vitro on cartilage stem cell cultures and in a mouse model of early osteoarthritis using an intra-articular injection approach (Srinivasan et al., 2012). Discovery of novel methods for activating stem cells in damaged cartilage will benefit a wide range of patients affected with chondral lesions and osteoarthritic pain.
During the past years, Dr. Kirn-Safran worked on the characterization of a mouse model expressing reduced levels of a proteoglycan, perlecan/Hspg2, which is abundant in developing bone and adult cartilage tissue. The phenotypic characterization of the perlecan/Hspg2-deficient mutant mice showed global skeletal growth deficiencies with increased calcification associated with decreased quality of adult bone (Lowe et al., 2014). Interestingly, perlecan/Hspg2, is found in the pericellular matrix of osteocytes (cells embedded in bone tissue) where it is beleived to function as a tethering element that detects and transduces signals to the bone cellular network (Wang et al., 2014). Current studies conducted in collaboration with Dr. Liyun Wang (UD, Department of Mechanical Engineering), who is a specialist in bone biomechanics, investigate the in vivo function of perlecan/Hspg2 as a mechanosensor of bone response to load. This work will determine whether this molecule is a drug target for the treatment of patients suffering from osteoporosis. In addition, other genetic and experimental mouse models developing chondral defects are studied to understand the molecular mechanisms regulating joint dysplasia syndromes and osteoarthritis, respectively.
- Delaware Rehabilitation Institute (DRI) Pilot, T-Type Calcium Channel: A novel target for treatment of osteoarthritis
- NIH R01-AR054385 (PI: L. Wang, Mechanical Engineering), Investigator: C. Kirn-Safran, Mechanosensing in the Bone Lacunar-Canalicular System.
Sucharitha Parthasarathy. Graduate Student. Use of experimental and genetic mouse model of osteoporosis to study the molecular mechanisms involved in disease progression and bone mechanosensation.
Akkiraju H, Srinivasan PP, Xu X, Jia J, Kirn-Safran C.B., Nohe A. CK2.1, a Bone Morphogenetic Protein Receptor Type Ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus. 2016; accepted in Stem Cell Research and Therapy.
- Lai X, Price C, Modla S, Thompson WR, Caplan J, Kirn-Safran CB, Wang L. The dependences of osteocyte network on bone compartment, age, and disease. Bone Res. 2015;3. pii: 15009.
- Srinivasan PP, Parajuli A, Price C, Wang L, Duncan RL, Kirn-Safran CB. Inhibition of T-Type Voltage Sensitive Calcium Channel Reduces Load-Induced OA in Mice and Suppresses the Catabolic Effect of Bone Mechanical Stress on Chondrocytes. PLoS One. 2015;10:e0127290.
- Lowe DA, Lepori-Bui N., Fomin PV, Sloofman LG, Zhou X., Farach-Carson MC, Wang L., Kirn-Safran CB. Deficiency in perlecan/HSPG2 during bone development enhances osteogenesis and decreases quality of adult bone in mice.. Calcified Tissue International and Musculoskeletal Research. 2014, 95:29-38.
- Aravindan RG, Kirn-Safran CB, Smith M., Martin-DeLeon P.A. Ultrastructural changes and asthenozoospermia in murine spermatozoa lacking the ribosomal protein L29/HIP gene. Asian Journal of Andrology 2014, 16:925-6
Wang B, Lai X, Price C, Thompson WR, Li W, Quabili TR, Tseng WJ, Liu XS, Zhang H, Pan J, Kirn-Safran CB, Farach-Carson MC, Wang L. Perlecan-containing pericellular matrix regulates solute transport and mechanosensing within the osteocyte lacunar-canalicular system. 2013 Sep.24.
- Jones DT, Lechertier T, Reynolds LE, Mitter R, Robinson SD, Kirn-Safran CB, Hodivala-Dilke KM. Endogenous ribosomal protein L29 (RPL29): a newly identified regulator of angiogenesis in mice. Dis Model Mech. 2013;6(1):115-24.
Srinivasan PP, McCoy SY, Jha AK, Yang W, Jia X, Farach-Carson MC, Kirn-Safran CB. Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis. Biomed Mater. 2012;7(2):024109.
- Keel S, Phelps S, Sabo K, O'Leary MN, Kirn-Safran CB, Abkowitz JL.Establishing Rps6 hemizygous mice as a model for studying how ribosomal protein haploinsufficiency impairs erythropoiesis. Establishing Rps6 hemizygous mice as a model for studying how ribosomal protein haploinsufficiency impairs erythropoiesis.Exp Hematol. 2012;40(4):290-4.
McCoy SY, Falgowski KA, Srinivasan PP, Thompson WR, Selva EM, Kirn-Safran CB. Serum xylosyltransferase 1 level increases during early posttraumatic osteoarthritis in mice with high bone forming potential. Bone (Special Issue on Osteoarthritis) 2011 Dec 2. [Epub ahead of print]
Thompson WR, Modla S, Grindel BJ, Czymmek KJ, Kirn-Safran CB, Wang L, Duncan RL, Farach-Carson MC. Perlecan/Hspg2 deficiency alters the pericellular space of the lacunocanalicular system surrounding osteocytic processes in cortical bone. J Bone Miner Res. 2011; 26(3):618-29.
Sloofman LG, Verdelis K, Spevak L, Zayzafoon M, Yamauchi M, Opdenaker LM, Farach-Carson MC, Boskey AL, Kirn-Safran CB. Effect of HIP/ribosomal protein L29 deficiency on mineral properties of murine bones and teeth. Bone. 2010;47(1):93-101.
Jha AK, Yang W, Kirn-Safran CB, Farach-Carson MC, Jia X. Perlecan domain I-conjugated, hyaluronic acid-based hydrogel particles for enhanced chondrogenic differentiation via BMP-2 release. Biomaterials. 2009 Dec;30(36):6964-75.
Kirn-Safran C, Farach-Carson MC, Carson DD. Multifunctionality of extracellular and cell surface heparan sulfate proteoglycans. Cell Mol Life Sci. 2009;66(21): 3421- 3434.
Oristian DS, Sloofman LG, Zhou X, Wang L, Farach-Carson MC, Kirn-Safran CB. Ribosomal protein L29/HIP deficiency delays osteogenesis and increases fragility of adult bone in mice. J Orthop Res. 2009;27(1):28–35.
Brown AJ, Alicknavitch M, D'Souza SS, et al. Heparanase expression and activity influences chondrogenic and osteogenic processes during endochondral bone formation. Bone. 2008;43(4):689–699.
Kirn-Safran CB, D'Souza SS, Carson DD. Heparan sulfate proteoglycans and their binding proteins in embryo implantation and placentation. Semin Cell Dev Biol. 2008;19(2):187–193.
Kirn-Safran CB, Oristian DS, Focht RJ, Parker SG, Vivian JL, Carson DD. Global growth deficiencies in mice lacking the ribosomal protein HIP/RPL29. Dev Dyn. 2007;236(2):447–460.
Kirn-Safran CB, Gomes RR, Brown AJ, Carson DD. Heparan sulfate proteoglycans: coordinators of multiple signaling pathways during chondrogenesis. Birth Defects Res C Embryo Today. 2004;72(1):69–88.
Miller SA, Brown AJ, Farach-Carson MC, Kirn-Safran CB. HIP/RPL29 down-regulation accompanies terminal chondrocyte differentiation. Differentiation. 2003;71(6):322–336.
Kirn-Safran CB, Julian J, Fongemie JE, Hoke DE, Czymmek KJC, Carson DD. Changes in the cytologic 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. Dev Dyn. 2002;223(1):70–84.
Kirn-Safran CB, Dayal S, Martin-DeLeon PA, Carson DD. Cloning, expression, and chromosome mapping of the murine Hip/Rpl29 gene. Genomics. 2000;68(2):210–219.
Kirn-Safran CB, Carson DD. Dynamics of uterine glycoconjugate expression and function. Semin Reprod Endocrinol. 1999;17(3):217–227.
Begue-Kirn C, Krebsbach PH, Bartlett JD, Butler WT. Dentin sialoprotein, dentin phosphoprotein, enamelysin and ameloblastin: tooth-specific molecules that are distinctively expressed during murine dental differentiation. Eur J Oral Sci. 1998;106(5):963–970.
Begue-Kirn C, Ruch JV, Ridall AL, Butler WT. Comparative analysis of mouse DSP and DPP expression in odontoblasts, preameloblasts, and experimentally induced odontoblast-like cells. Eur J Oral Sci. 1998;106 Suppl 1:254–259.
Heikinheimo K, Begue-Kirn C, Ritvos O, Tuuri T, Ruch JV. Activin and bone morphogenetic protein (BMP) signalling during tooth development. Eur J Oral Sci. 1998;106 Suppl 1:167–173.
Hoke DE, Regisford EG, Julian J, Amin A, Begue-Kirn C, Carson DD. Murine HIP/L29 is a heparin-binding protein with a restricted pattern of expression in adult tissues. J Biol Chem. 1998;273(39):25148–25157.
Sun ZL, Fang DN, Wu XY, et al. Expression of dentin sialoprotein (DSP) and other molecular determinants by a new cell line from dental papillae, MDPC-23. Connect Tissue Res. 1998;37(3-4):251–261.
Heikinheimo K, Begue-Kirn C, Ritvos O, Tuuri T, Ruch JV. The activin-binding protein follistatin is expressed in developing murine molar and induces odontoblast-like cell differentiation in vitro. J Dent Res. 1997;76(10):1625–1636.
Smith AJ, Cassidy N, Perry H, Begue-Kirn C, Ruch JV, Lesot H. Reactionary dentinogenesis. Int J Dev Biol. 1995;39(1):273–280.
Smith AJ, Tobias RS, Cassidy N, Begue-Kirn C, Ruch JV, Lesot H. Influence of substrate nature and immobilization of implanted dentin matrix components during induction of reparative dentinogenesis. Connect Tissue Res. 1995;32(1-4):291–296.
Begue-Kirn C, Smith AJ, Loriot M, Kupferle C, Ruch JV, 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. Int J Dev Biol. 1994;38(3):405–420.
Lesot H, Begue-Kirn C, Kubler MD, et al. Experimental Induction Of Odontoblast Differentiation And Stimulation During Reparative Processes. Cells Mat. 1993;3(2):201–217.
Begue-Kirn C, Smith AJ, Ruch JV, et al. Effects of dentin proteins, transforming growth factor beta 1 (TGF beta 1) and bone morphogenetic protein 2 (BMP2) on the differentiation of odontoblast in vitro. Int J Dev Biol. 1992;36(4):491–503.
- US-2014/0005111-A1 application entitled “Injectable Delivery System for Heparan-Binding Growth Factors” issued February 2017.
Phone: (302) 831-3249
Fax: (302) 831-2281
Office: 310 Wolf Hall
Lab: 251 McKinly
Department of Biological Sciences
University of Delaware
Newark, DE 19716
- B.S., M.S., Ph.D. - University of Strasbourg, France
- Postdoctoral - University of Texas-Houston, Dental Branch and M.D. Anderson Cancer Center