- American Society for Clinical Investigation, 1969
- Lederle Medical Faculty Award, 1968-1971
- Research Career Development Award, 1969-1974
- Travel Awards, International Congress of Biochemistry, 1967; 1970; 1973
- Association of American Physicians, 1974
- Josiah Macy Faculty Scholar Award, 1975
- John Simon Guggenheim Memorial Fellowship, 1985
- MERIT Award, National Institute of Arthritis, Musculoskeletal and Skin Diseases, 1989
- President, International Society for Matrix Biology, 2001-2003
- Vice-President and President-elect, American Society for Matrix Biology, 2001-2003; President, 2003-2004
- Solomon Berson Alumni Achievement Award in Basic Science, New York University School of Medicine, 2004
The major interest of the group is to understand how cell-matrix interactions influence the cellular function of fibroblasts, osteoblasts, endothelial cells, and smooth muscle cells. In the past the group has been involved in the identification and characterization of a number of extracellular matrix proteins, including collagens and thrombospondins, and has studied the regulation of expression and the response of the genes encoding these proteins to growth factors and cytokines. More recently, we have used the approach of targeted disruption of genes by homologous recombination (gene knock-outs) to study the functions of thrombospondins 2 and 3. Thrombospondin 2-null mice display a wide spectrum of connective tissue and vascular abnormalities, includingaltered collagen fibrillogenesis, increased angiogenesis, and a bleeding diathesis, and fibroblasts from these mice show adhesive defects. The biochemical basis for these changes is under investigation. We have also generated mutations in regulatory regions of a type I collagen gene by homologous recombination (gene knock-ins) to study the effects of these mutations in mice.
Agah A, Kyriakides TR, Bornstein P (2005) Proteolysis of cell-surface tissue transglutaminase by matrix metalloproteinase-2 contributes to the adhesive defect and matrix abnormalities in thrombospondin-2-null fibroblasts and mice. Am J Pathol 167: 81-88.
Chen J, Somanath PR, Razorenova O, Chen WS, Hay N, Bornstein P, Byzova TV (2005) Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo. Nat Med 11: 1188-1196.
Christopherson KS, Ullian EM, Stokes CC, Mullowney CE, Hell JW, Agah A, Lawler J, Mosher DF, Bornstein P, Barres BA (2005) Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 120: 421-433.
Fears CY, Grammer JR, Stewart JE, Jr., Annis DS, Mosher DF, Bornstein P, Gladson CL (2005) Low-density lipoprotein receptor-related protein contributes to the antiangiogenic activity of thrombospondin-2 in a murine glioma model. Cancer Res 65: 9338-9346.
Hankenson KD, Ausk BJ, Bain SD, Bornstein P, Gross TS, Srinivasan S (2005) Mice lacking thrombospondin 2 show an atypical pattern of endocortical and periosteal bone formation in response to mechanical loading. Bone [Nov 11; Epub ahead of print]
Hankenson KD, James IE, Apone S, Stroup GB, Blake SM, Liang X, Lark MW, Bornstein P (2005) Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombospondin-2-null mice. Matrix Biol 24: 362-370.
Kalas W, Yu JL, Milsom C, Rosenfeld J, Benezra R, Bornstein P, Rak J (2005) Oncogenes and Angiogenesis: down-regulation of thrombospondin-1 in normal fibroblasts exposed to factors from cancer cells harboring mutant ras. Cancer Res 65: 8878-8886.
Puolakkainen PA, Bradshaw AD, Brekken RA, Reed MJ, Kyriakides T, Funk SE, Gooden MD, Vernon RB, Wight TN, Bornstein P, Sage EH (2005) SPARC-thrombospondin-2-double-null mice exhibit enhanced cutaneous wound healing and increased fibrovascular invasion of subcutaneous polyvinyl alcohol sponges. J Histochem Cytochem 53: 571-581.
Agah A, Kyriakides TR, Letrondo N, Bjorkblom B, Bornstein P (2004) Thrombospondin 2 levels are increased in aged mice: consequences for cutaneous wound healing and angiogenesis. Matrix Biol 22: 539-547.
Bornstein P, Agah A, Kyriakides TR (2004) The role of thrombospondins 1 and 2 in the regulation of cell-matrix interactions, collagen fibril formation, and the response to injury. Int J Biochem Cell Biol 36: 1115-1125.
Cursiefen C, Masli S, Ng TF, Dana MR, Bornstein P, Lawler J, Streilein JW (2004) Roles of thrombospondin-1 and -2 in regulating corneal and iris angiogenesis. Invest Ophthalmol Vis Sci 45: 1117-1124.
Kokenyesi R, Armstrong LC, Agah A, Artal R, Bornstein P (2004) Thrombospondin 2 deficiency in pregnant mice results in premature softening of the uterine cervix. Biol Reprod 70: 385-390.
Rahkonen O, Su M, Hakovirta H, Koskivirta I, Hormuzdi SG, Vuorio E, Bornstein P, Penttinen R (2004) Mice with a deletion in the first intron of the Col1a1 gene develop age-dependent aortic dissection and rupture. Circ Res 94: 83-90.
Schroen B, Heymans S, Sharma U, Blankesteijn WM, Pokharel S, Cleutjens JP, Porter JG, Evelo CT, Duisters R, van Leeuwen RE, Janssen BJ, Debets JJ, Smits JF, Daemen MJ, Crijns HJ, Bornstein P, Pinto YM (2004) Thrombospondin-2 is essential for myocardial matrix integrity: increased expression identifies failure-prone cardiac hypertrophy. Circ Res 95: 515-522.
Armstrong LC, Bornstein P (2003) Thrombospondins 1 and 2 function as inhibitors of angiogenesis. Matrix Biol 22: 63-71. Kalas W, Gilpin S, Yu JL, May L, Krchnakova H, Bornstein P, Rak J (2003) Restoration of thrombospondin 1 expression in tumor cells harbouring mutant ras oncogene by treatment with low doses of doxycycline. Biochem Biophys Res Commun 310: 109-114.
Kyriakides TR, Bornstein P (2003) Matricellular proteins as modulators of wound healing and the foreign body response. Thromb Haemost 90: 986-992.
Kyriakides TR, Rojnuckarin P, Reidy MA, Hankenson KD, Papayannopoulou T, Kaushansky K, Bornstein P (2003) Megakaryocytes require thrombospondin-2 for normal platelet formation and function. Blood 101: 3915-3923.
Puolakkainen P, Bradshaw AD, Kyriakides TR, Reed M, Brekken R, Wight T, Bornstein P, Ratner B, Sage EH (2003) Compromised production of extracellular matrix in mice lacking secreted protein, acidic and rich in cysteine (SPARC) leads to a reduced foreign body reaction to implanted biomaterials. Am J Pathol 162: 627-635.
Armstrong LC, Bjorkblom B, Hankenson KD, Siadak AW, Stiles CE, Bornstein P (2002) Thrombospondin 2 inhibits microvascular endothelial cell proliferation by a caspase-independent mechanism. Mol Biol Cell 13: 1893-1905.
Hankenson KD, Bornstein P (2002) The secreted protein thrombospondin 2 is an autocrine inhibitor of marrow stromal cell proliferation. J Bone Miner Res 17: 415-425.
Lange-Asschenfeldt B, Weninger W, Velasco P, Kyriakides TR, von Andrian UH, Bornstein P, Detmar M (2002) Increased and prolonged inflammation and angiogenesis in delayed-type hypersensitivity reactions elicited in the skin of thrombospondin-2–deficient mice. Blood 99: 538-545.