Our primary focus concerns the role of cytokines released by bone marrow stromal cells in hematopoiesis and bone remodeling. We are interested in the molecular mechanisms involved in the regulation of several factors produced by stromal cells including macrophage colony stimulating factor and platelet derived growth factor. Recently, we have initiated studies to determine if stromal cells may be utilized as a vehicle to target genes to the bone microenvironment using retroviral-mediated gene transfer technology. We are also examining the regulation of IGF-I and IGF-binding proteins (IGFBPs) in stromal cells and certain tumors. The effect of IGFBP-4 on IGF-I-mediated events in normal and pathologic conditions will be explored. Our studies will also examine the relative contribution of transcriptional and posttranscriptional mechanisms to the regulation of IGFBP mRNAs in response to cytokines.

Retroviral gene transfer, Cell transfection, Northern blot analysis, RNase protection assay, Western ligand and immunoblot analysis, cell culture (primary stromal, established cell lines, stromal/osteoclast coculture).

Abboud SL: Regulation of platelet-derived growth factor (PDGF) A and B chain gene expression in bone marrow stromal cells. J Cell Physiol 164:434-440, 1995.

Grellier PC, Yee D, Gonzales M, Abboud SL: Characterization of insulin-like growth factor binding proteins (IGFBPs) and regulation of IGFBP-4 in bone marrow stromal cells. Brit J Haematol 90:249-257, 1995.

Grellier P, Feliers D, Yee D, Woodruff K, Abboud S: Interaction between insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBPs) in TC-1 stromal cells. J Endocrinology 149:519-529, 1996.

Grellier P, Sabbah M, Fouqueray B, Woodruff K, Yee D, Abboud H, Abboud SL: Characterization of insulin-like growth factor binding proteins (IGFBPs) and regulation of IGFBP3 in human mesangial cells. Kidney Int. 49:1071-1078, 1996.

Kasinath BS, Grellier PC, Choudhury GG, Abboud SL: Regulation of basement membrane heparan sulfate proteoglycan gene expression by high glucose medium in glomerular epithelial cells. J Cell Physiol 167:131-136, 1996.

Grellier P, Chanson P, Casadevall N, Abboud S, Schaison G: Polycythemia vera (PV) in a patient with acromegaly: remission of PV after successful surgical removal of a growth hormone-secreting adenoma. Ann Int Med 124:495-496, 1996.

Park IS, Kiyomoto H, Abboud SL, Abboud HE: Expression of transforming growth factor (TGF)-betal and type IV collagen in early streptozotocin-induced diabetes. Diabetes 46:473-480, 1997.

stromal cells, hematopoiesis, bone, M-CSF, IGF-I, IGF-binding proteins, PDGF