Areas of Interest
My laboratory's research activities center on developing an
understanding of the molecular mechanisms regulating the normal
development, differentiation and maintenance of connective
tissue. The experimental approach we have selected to dissect
this problem is the identification and cloning of genetic units
that regulate the biosynthesis of extracellular matrix
macromolecules. Once identified and isolated, the nature of the
macromolecules encoded by these genetic elements can be
appreciated and an understanding of their mechanism(s) of action
at the molecular level can be developed. Presently, we are
studying two different mutations in the mouse that affect the
biosynthesis of collagen and other extracellular matrix
macromolecules in several tissues including skin, bone, and
heart. We are pursuing a positional cloning strategy for their
isolation that includes an interspecific backcross analysis to
develop a high resolution molecular genetic map for the loci as
well as analyzing a series of transgenic mice bearing various
collagen transgene constructs to develop an understanding of the
interaction of the mutant gene product with collagen producing
connective tissue cells.
Selected Publications
Kalajzic I, Terzic J, Rumboldt Z, Mack K, Naprta A, Ledgard F,
Gronowicz G, Clark SH, Rowe DW. 2002. Osteoblastic response to
the defective matrix in the osteogenesis imperfecta murine (oim)
mouse. Endocrinology. May;143(5):1594-601.
Kalajzic I, Kalajzic Z, Kaliterna M, Gronowicz G, Clark SH,
Lichtler AC, Rowe D. 2002. Use of type I collagen green
fluorescent protein transgenes to identify subpopulations of
cells at different stages of the osteoblast lineage. J Bone
Miner Res. Jan;17(1):15-25.
Visnjic D, Kalajzic I, Gronowicz G, Aguila HL, Clark SH,
Lichtler AC, Rowe DW. 2001. Conditional ablation of the
osteoblast lineage in Col2.3deltatk transgenic mice. J Bone
Miner Res. 2001 Dec;16(12):2222-31.
Stover ML, Wang CK, McKinstry MB, Kalajzic I, Gronowicz G,
Clark SH, Rowe DW, Lichtler AC. 2001. Bone-directed expression
of Col1a1 promoter-driven self-inactivating retroviral vector in
bone marrow cells and transgenic mice. Mol Ther.
Apr;3(4):543-50.
Dodig TD, Mack KT, Cassarino DF, Clark SH. 2001. Development
of the tight-skin phenotype in immune-deficient mice. Arthritis
Rheum. Mar;44(3):723-7.
Bogdanovic Z, Huang YF, Dodig M, Clark SH, Lichtler AC, Kream
BE. 2000. Parathyroid hormone inhibits collagen synthesis and
the activity of rat col1a1 transgenes mainly by a cAMP-mediated
pathway in mouse calvariae. J Cell Biochem. Feb;77(1):149-58. |
