Gary Balian
Mary Muilenberg Stamp Professor of Orthopaedic Research and
Professor of Biochemistry & Molecular Genetics
Ph.D., University of London
Biochemistry of Connective Tissue Macromolecules

 

Prostate cancer cell-bone marrow adhesion mediators — We have discovered several small peptides that, when injected into the blood circulation, will target bone; the peptides are unique and bind to bone preferentially. In laboratory experiments, one of these peptides decreases the binding of prostate cancer cells to bone marrow endothelial cells that line the bone marrow cavity, suggesting that the peptides may prevent the spread of cancer. Determination of the effects of bone tropic peptides on cell attachment and invasion is particularly relevant to the cancer field. Identification of targeting peptides and their ligands will provide basic information towards understanding the mechanisms of metastases to bone. Contributions to our understanding of cancer cell homing to bone may be forthcoming from the identification of the targets in bone that serve as the destination for the peptides. The peptides may mimic the segment of a protein that exhibits bone targeting characteristics. This information could be an essential part of the effort to understand the mechanisms that underlie cell adhesion and invasion in cancer.

Bone repair and regeneration — Cancer cell metastases are by no means the only area of relevance of this study. Bone repair is clearly a very important area of consideration in the field of musculoskeletal tissue regeneration. The biomimetic properties of bone tropic factors could create a technological step forward in the field of tissue engineering, as well as for prosthetic surgery of bone. Inclusion of bone targeting factors in synthetic or natural polymers may assist specificity of cell adherence, thereby scavenging endogenous cells within tissues that are undergoing repair and regeneration. Further development of this approach can lead to the discovery and development of biologically active compounds that target bone and potentiate repair through mechanisms that are well characterized biologically at the cellular and molecular levels.

Anabolic Effect of Osteogenic Peptides — We have shown that two unique bone targeting peptides potentiate the differentiation of mesenchymal cells in vitro, moreover, the peptides promote bone repair in critical sized unicortical defects. We have identified the molecular targets for these peptides in mesenchymal cells, and our analysis of the data suggest that certain metabolic pathways are involved through which the peptides exert their osteogenic effects. We will investigate the potential anabolic effects of these novel peptides on bone density and gene expression.


Selected References

Yang X, Wang D, Hao J, Gong M, Arlet V, Balian G, Shen F, Li XJ. (2011) "Enhancement of matrix production and cell proliferation in human annulus cells in rotating bioreactor culture." Tissue Eng Part A. Feb [Epub ahead of print] [PubMed]

Keller TC, Hogan MV, Kesturu G, James R, Balian G, Chhabra AB. (2011) "Growth/differentiation factor-5 modulates the synthesis and expression of extracellular matrix and cell-adhesion-related molecules of rat Achilles tendon fibroblasts." Connect Tissue Res. Jan [Epub ahead of print] [PubMed]

Wang X, Cui F, Madhu V, Dighe AS, Balian G, Cui Q. (2011) "Combined VEGF and LMP-1 delivery enhances osteoprogenitor cell differentiation and ectopic bone formation." Growth Factors. 29:36-48. [PubMed]

Balian G, Beck G, Madhu V, Sikes R, Cui Q, Liang H, Bush J. (2010) "Peptides from phage display library modulate gene expression in mesenchymal cells and potentiate osteogenesis in unicortical bone defects." J Vis Exp. Dec (46) [PubMed]

Hogan M, Girish K, James R, Balian G, Hurwitz S, Chhabra AB. (2010) "Growth differentiation factor-5 regulation of extracellular matrix gene expression in murine tendon fibroblasts." J Tissue Eng Regen Med. Jul [Epub ahead of print] [PubMed]

Liang H, Wang K, Shimer AL, Li X, Balian G, Shen FH. (2010) "Use of a bioactive scaffold for the repair of bone defects in a novel reproducible vertebral body defect model." Bone. 47:197-204. Epub 2010 May 24. [PubMed]

Park A, Hogan MV, Kesturu GS, James R, Balian G, Chhabra AB. (2010) "Adipose-derived mesenchymal stem cells treated with growth differentiation factor-5 express tendon-specific markers." Tissue Eng Part A. 16:2941-51. [PubMed]

Cui F, Wang X, Liu X, Dighe AS, Balian G, Cui Q. (2010) "VEGF and BMP-6 enhance bone formation mediated by cloned mouse osteoprogenitor cells." Growth Factors. 28:306-17. [PubMed]

Santos JL, Pandita D, Rodrigues J, Pego AP, Granja PL, Balian G, Tomas H. (2010) "Receptor-mediated gene delivery using PAMAM dendrimers conjugated with peptides recognized by mesenchymal stem cells." Mol Pharm. Jun 7:763-74. [PubMed]