D.V.M. - University of Illinois, College of Veterinary Medicine, Champaign, IL (1988-92)
M.S. - Purdue University, School of Veterinary Medicine, Department of Basic Medical Sciences, West Lafayette, IN (1994-1997)
Ph.D. - University of Washington, School of Medicine, Department of Biochemistry, Seattle, WA, PhD. (1997-2001)

Although the ECM plays a crucial role in tissue structure and cell adhesion, the ECM also dynamically affects cell function.  In particular, a group of ECM proteins termed matricellular proteins (MP) are highly expressed in the skeleton, but do not play a primary structural role.  MP bind the structural matrix, growth factors, extracellular proteases and cell surface receptors.  For our studies we use the MP, thrombospondin-2 (TSP2) as a model.  Mice with a disruption of the TSP2 gene (TSP2-null) show a variety of interesting phenotypes including defects in platelet function, collagen fibrilogenesis, fibroblast adhesion, and bone formation.  Most notably these mice have a defect in MSC number and differentiation.  MSC are osteoblast precursors that also differentiate to become adipocytes, chondrocytes, and hematopoietic support cells.  Given the complexity of MP structure and molecular interactions, on-going studies with TSP2 seek to better define the contextual role of its function.    We are generating two different transgenic mouse models to evaluate TSP2 in a spatially and temporally defined manner and to quantitatively follow TSP2 gene expression in vivo.  Studies in vitro are using a structure-function approach with domain deletions and siRNA to determine molecular mechanism of TSP2 function.  Finally, we are exploring the regulation of TSP2 gene expression in association with MSC differentiation.

Our initial work with TSP2 opened a new research area focused on MSC biology.   Marrow-derived MSC are a poorly understood cell type, and we seek to better define factors – including ECM, growth factors, and transcriptional networks - that define the MSC niche and regulate proliferation and differentiation.  Particularly we are interested in the reciprocal, terminal fates of osteoblastogenesis and adipogenesis.  In a variety of bone disorders (most notably osteoporosis), adipocytes increase in number at the apparent expense of osteoblasts.  Furthermore, we are attempting to refine techniques for the identification, culture, and in vivo study of MSC and for developing the use of MSC therapeutically to repair bone defects.  On going studies that are related to MSC, include (1) evaluating the effects of bone sialoprotein (BSP) on MSC differentiation; (2) studying transcriptional networks activated by BMP6 in human MSC using a combinatorial approach; (3) using microPET imaging to follow primary MSC localization in vivo; and (4) examining the significance of MSC adhesion to engineered biomaterials and natural substrates in controlling fate determination.

2:  Alford AI, Hankenson KD.   Matricellular proteins: extracellular modulators of bone development, remodeling, and regeneration. Bone. 2006 Jun;38(6):749-57.

3:  Friedman MS, Long MW, Hankenson KD.  Osteogenic differentiation of human mesenchymal stem cells is regulated by bone morphogenetic protein-6. J Cell Biochem. 2006 Jun 1;98(3):538-54.

4:  Hankenson KD, Ausk BJ, Bain SD, Bornstein P, Gross TS, Srinivasan S.
 Mice lacking thrombospondin 2 show an atypical pattern of endocortical and
periosteal bone formation in response to mechanical loading.  Bone. 2006 Mar;38(3):310-6.

5:  Hankenson KD, James IE, Apone S, Stroup GB, Blake SM, Liang X, Lark MW,
Bornstein P.  Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombospondin-2-null mice. Matrix Biol. 2005 Aug;24(5):362-70.

6:  Hankenson KD, Hormuzdi SG, Meganck JA, Bornstein P.  Mice with a disruption of the thrombospondin 3 gene differ in geometric and biomechanical properties of bone and have accelerated development of the femoral head. Mol Cell Biol. 2005 Jul;25(13):5599-606.

7:  Bennett CN, Longo KA, Wright WS, Suva LJ, Lane TF, Hankenson KD, MacDougald OA.  Regulation of osteoblastogenesis and bone mass by Wnt10b.
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3324-9.

8:  Chamberlain JR, Schwarze U, Wang PR, Hirata RK, Hankenson KD, Pace JM,
Underwood RA, Song KM, Sussman M, Byers PH, Russell DW.  Gene targeting in stem cells from individuals with osteogenesis imperfecta. Science. 2004 Feb 20;303(5661):1198-201.