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Faculty
 Stephen
H. Clark
Associate Professor Genetics and Developmental Biology
sclark@nso2.uchc.edu
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. |
