Gary Balian

Primary Appointment

Professor Emeritus, Orthopaedic Surgery

Education

  • BS, Biochemistry, Queen Elizabeth College, Univ. of London, London, England
  • PhD, Biochemistry, University of London, London, England
  • Postdoc, Biochemistry, University of Washington, Seattle, Washington

Research Interests

Targeted delivery to cells and tissues

Research Description

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.

Personal Statement

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 Publications

Dighe AS, Yang S, Madhu V, Balian G, Cui Q, Interferon gamma and T cells inhibit osteogenesis induced by allogeneic mesenchymal stromal cells., 2012; Journal of orthopaedic research : official publication of the Orthopaedic Research Society. () . PMID: 22886855 | PMCID: NIHMS396283

James R, Kumbar SG, Laurencin CT, Balian G, Chhabra AB, Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems., 2011; Biomedical materials (Bristol, England). 6(2) 025011. PMID: 21436509 | PMCID: PMC3206634

Liang H, Ma SY, Mohammad K, Guise TA, Balian G, Shen FH, The reaction of bone to tumor growth from human breast cancer cells in a rat spine single metastasis model., 2011; Spine. 36(7) 497-504. PMID: 21422981 | PMCID: NIHMS340933

Keller TC, Hogan MV, Kesturu G, James R, Balian G, Chhabra AB, Growth/differentiation factor-5 modulates the synthesis and expression of extracellular matrix and cell-adhesion-related molecules of rat Achilles tendon fibroblasts., 2011; Connective tissue research. 52(4) 353-64. PMID: 21250863

Wang X, Cui F, Madhu V, Dighe AS, Balian G, Cui Q, Combined VEGF and LMP-1 delivery enhances osteoprogenitor cell differentiation and ectopic bone formation., 2011; Growth factors (Chur, Switzerland). 29(1) 36-48. PMID: 21222516

Yang X, Wang D, Hao J, Gong M, Arlet V, Balian G, Shen FH, Li XJ, Enhancement of matrix production and cell proliferation in human annulus cells under bioreactor culture., 2011; Tissue engineering. Part A. 17(11) 1595-603. PMID: 21303231 | PMCID: 21303231

Hogan M, Girish K, James R, Balian G, Hurwitz S, Chhabra AB, Growth differentiation factor-5 regulation of extracellular matrix gene expression in murine tendon fibroblasts., 2010; Journal of tissue engineering and regenerative medicine. 5(3) 191-200. PMID: 20653042

Liang H, Wang K, Shimer AL, Li X, Balian G, Shen FH, Use of a bioactive scaffold for the repair of bone defects in a novel reproducible vertebral body defect model., 2010; Bone. 47(2) 197-204. PMID: 20580872 | PMCID: 20580872

Wan Y, Feng G, Shen FH, Balian G, Laurencin CT, Li X, Novel biodegradable poly(1,8-octanediol malate) for annulus fibrosus regeneration., 2007; Macromolecular bioscience. 7(11) 1217-24. PMID: 17683110

Cui M, Wan Y, Anderson DG, Shen FH, Leo BM, Laurencin CT, Balian G, Li X, Mouse growth and differentiation factor-5 protein and DNA therapy potentiates intervertebral disc cell aggregation and chondrogenic gene expression., 2007; The spine journal : official journal of the North American Spine Society. 8(2) 287-95. PMID: 17974491 | PMCID: 17974491

Zeng Q, Li X, Beck G, Balian G, Shen FH, Growth and differentiation factor-5 (GDF-5) stimulates osteogenic differentiation and increases vascular endothelial growth factor (VEGF) levels in fat-derived stromal cells in vitro., 2006; Bone. 40(2) 374-81. PMID: 17070126 | PMCID: 17070126

Cui Q, Xiao Z, Li X, Saleh KJ, Balian G, Use of genetically engineered bone-marrow stem cells to treat femoral defects: an experimental study., 2006; The Journal of bone and joint surgery. American volume. 88() 167-72. PMID: 17079384 | PMCID: 17079384

Shen FH, Zeng Q, Lv Q, Choi L, Balian G, Li X, Laurencin CT, Osteogenic differentiation of adipose-derived stromal cells treated with GDF-5 cultured on a novel three-dimensional sintered microsphere matrix., 2006; The spine journal : official journal of the North American Spine Society. 6(6) 615-23. PMID: 17088192 | PMCID: 17088192

Zeng Q, Li X, Choi L, Beck G, Balian G, Shen FH, Recombinant growth/differentiation factor-5 stimulates osteogenic differentiation of fat-derived stromal cells in vitro., 2006; Connective tissue research. 47(5) 264-70. PMID: 17118748 | PMCID: 17118748