Paul Bornstein

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University of Washington
School of Medicine
Medicine
ProfessorAppointed: 1974
University of Washington
School of Medicine
Biochemistry
ProfessorAppointed: 1974

Mailing Address

Box 357350
University of Washington
Seattle, Washington 98195
United States

Contact Information

Phone: (206) 543-1789
Fax: (206) 685-4426
bornsten@u.washington.edu

Qualifications

M.D., New York University, 1958.

Expertise and Research Interests

The major interest of the laboratory is to understand how cell-matrix interactions influence the functions of mesenchymal cells such as fibroblasts, endothelial cells, and smooth muscle cells. In the past the laboratory 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 the thrombospondins. Thrombospondin 2-null mice display a wide spectrum of connective tissue and vascular abnormalities, including altered 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. Finally we are engaged in an investigation of mammalian mitochondrial import.

Keywords

COS Keywords:

Cardiovascular Biology, Cell Biology, Cell Differentiation, Connective Tissue, Gene Expression, Gene Regulation, Genes, Growth Factor Receptors, Growth Factors, Immunobiology, Immunology, Trauma, Cell Biology.

Additional Terms:

Cardiovascular Biology, Cartilage, Cell Biology, Cell Differentiation, Cell Growth, Cell-cell Interactions, Connective Tissue, Fibrous, Gene Expression, Gene Regulation, Genes, Growth Factor Receptors, Growth Factors, Immunobiology, Immunology, Specific Cell Types.

Publications

  • Armstrong LC, Saenz AJ, Bornstein P, Metaxin 1 interacts with metaxin 2, a novel related protein associated with the mammalian mitochondrial outer membrane., Journal of Cell Biochemistry, 74(1), 11-22, 1 Jul 1999 Abstract
  • Kyriakides TR, Leach KJ, Hoffman AS, Ratner BD, Bornstein P, Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity., Proceedings of the National Academy of Sciences (USA), 96(8), 4449-54, 13 Apr 1999 Abstract
  • Kyriakides T R, Zhu Y H, Yang Z, Bornstein P, The distribution of the matricellular protein thrombospondin 2 in tissues of embryonic and adult mice., Journal of Histochemistry and Cytochemistry, 46(9), 1007-15, September 1998 Abstract
  • Collins M, Rojnuckarin P, Zhu Y H, Bornstein P, A far upstream, cell type-specific enhancer of the mouse thrombospondin 3 gene is located within intron 6 of the adjacent metaxin gene., Journal of Biological Chemistry, 273(34), 21816-24, 21 Aug 1998 Abstract
  • Hormuzdi S G, Penttinen R, Jaenisch R, Bornstein P, A gene-targeting approach identifies a function for the first intron in expression of the alpha1(I) collagen gene., Molecular and Cellular Biology, 18(6), 3368-75, June 1998 Abstract
  • Hormuzdi SG, Penttinen R, Jaenisch R, Bornstein P, A gene-targeting approach identifies a function for the first intron in expression of the alpha1\(I\) collagen gene., Molecular and Cellular Biology, 18(6), 3368-75, 1998 Abstract
  • Kyriakides T R, Zhu Y H, Smith L T, Bain S D, Yang Z, Lin M T, Danielson K G, Iozzo R V, LaMarca M, McKinney C E, Ginns E I, Bornstein P, Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis., Journal of Cell Biology, 140(2), 419-30, 26 Jan 1998 Abstract
  • Adolph K W, Liska D J, Bornstein P, Analysis of the promoter and transcription start sites of the human thrombospondin 2 gene (THBS2)., Gene, 193(1), 5-11, 1 Jul 1997 Abstract
  • Liu X, Wu H, Loring J, Hormuzdi S, Disteche C M, Bornstein P, Jaenisch R, Trisomy eight in ES cells is a common potential problem in gene targeting and interferes with germ line transmission., Developmental Dynamics, 209(1), 85-91, May 1997 Abstract
  • Armstrong L C, Komiya T, Bergman B E, Mihara K, Bornstein P, Metaxin is a component of a preprotein import complex in the outer membrane of the mammalian mitochondrion., Journal of Biological Chemistry, 272(10), 6510-8, 7 Mar 1997 Abstract
  • Collins M, Bornstein P, SP1-binding elements, within the common metaxin-thrombospondin 3 intergenic region, participate in the regulation of the metaxin gene., Nucleic Acids Research, 24(19), 3661-9, 1 Oct 1996 Abstract
  • Long G L, Winfield S, Adolph K W, Ginns E I, Bornstein P, Structure and organization of the human metaxin gene (MTX) and pseudogene., Genomics, 33(2), 177-84, 15 Apr 1996 Abstract
  • Bornstein P, Regulation of expression of the alpha 1 (I) collagen gene: a critical appraisal of the role of the first intron [see comments], Matrix Biology, 15(1), 3-10, April 1996 Abstract
  • Iruela-Arispe M L, Porter P, Bornstein P, Sage E H, Thrombospondin-1, an inhibitor of angiogenesis, is regulated by progesterone in the human endometrium., Journal of Clinical Investigation, 97(2), 403-12, 15 Jan 1996 Abstract
  • Hugo C, Pichler R, Meek R, Gordon K, Kyriakides T, Floege J, Bornstein P, Couser W G, Johnson R J, Thrombospondin 1 is expressed by proliferating mesangial cells and is up-regulated by PDGF and bFGF in vivo., Kidney International, 48(6), 1846-56, December 1995 Abstract
  • Houglum K, Buck M, Alcorn J, Contreras S, Bornstein P, Chojkier M, Two different cis-acting regulatory regions direct cell-specific transcription of the collagen alpha 1(I) gene in hepatic stellate cells and in skin and tendon fibroblasts., Journal of Clinical Investigation, 96(5), 2269-76, November 1995 Abstract
  • Vos H L, Mockensturm-Wilson M, Rood P M, Maas A M, Duhig T, Gendler S J, Bornstein P, A tightly organized, conserved gene cluster on mouse chromosome 3 (E3-F1)., Mammalian Genome, 6(11), 820-2, November 1995 Abstract
  • Reed M J, Iruela-Arispe L, O'Brien E R, Truong T, LaBell T, Bornstein P, Sage E H, Expression of thrombospondins by endothelial cells. Injury is correlated with TSP-1., American Journal of Pathology, 147(4), 1068-80, October 1995 Abstract
  • Bornstein P, Diversity of function is inherent in matricellular proteins: an appraisal of thrombospondin 1., Journal of Cell Biology, 130(3), 503-6, August 1995 Abstract
  • Slack J L, Parker M I, Bornstein P, Transcriptional repression of the alpha 1(I) collagen gene by ras is mediated in part by an intronic AP1 site., Journal of Cellular Biochemistry, 58(3), 380-92, July 1995 Abstract
  • Adolph K W, Long G L, Winfield S, Ginns E I, Bornstein P, Structure and organization of the human thrombospondin 3 gene (THBS3)., Genomics, 27(2), 329-36, 20 May 1995 Abstract
  • Bornstein P, McKinney C E, LaMarca M E, Winfield S, Shingu T, Devarayalu S, Vos H L, Ginns E I, Metaxin, a gene contiguous to both thrombospondin 3 and glucocerebrosidase, is required for embryonic development in the mouse: implications for Gaucher disease., Proceedings of the National Academy of Sciences (USA), 92(10), 4547-51, 9 May 1995 Abstract
  • Shingu T, Bornstein P, Overlapping Egr-1 and Sp1 sites function in the regulation of transcription of the mouse thrombospondin 1 gene., Journal of Biological Chemistry, 269(51), 32551-7, 23 Dec 1994 Abstract
  • Slack J L, Bornstein P, Transformation by v-src causes transient induction followed by repression of mouse thrombospondin-1., Cell Growth and Differentiation, 5(12), 1373-80, December 1994 Abstract
  • Liska D J, Reed M J, Sage E H, Bornstein P, Cell-specific expression of alpha 1(I) collagen-hGH minigenes in transgenic mice., Journal of Cell Biology, 125(3), 695-704, May 1994 Abstract
  • Liska D J, Hawkins R, Wikstrom K, Bornstein P, Modulation of thrombospondin expression during differentiation of embryonal carcinoma cells., Journal of Cellular Physiology, 158(3), 495-505, March 1994 Abstract
  • Bornstein P, Sage E H, Thrombospondins., Methods In Enzymology, 245, 62-85, 1994 Abstract
  • Reed M J, Puolakkainen P, Lane T F, Dickerson D, Bornstein P, Sage E H, Differential expression of SPARC and thrombospondin 1 in wound repair: immunolocalization and in situ hybridization., Journal of Histochemistry and Cytochemistry, 41(10), 1467-77, October 1993 Abstract
  • Iruela-Arispe M L, Liska D J, Sage E H, Bornstein P, Differential expression of thrombospondin 1, 2, and 3 during murine development., Developmental Dynamics, 197(1), 40-56, May 1993 Abstract
  • Shingu T, Bornstein P, Characterization of the mouse thrombospondin 2 gene., Genomics, 16(1), 78-84, April 1993 Abstract
  • Framson P, Bornstein P, A serum response element and a binding site for NF-Y mediate the serum response of the human thrombospondin 1 gene., Journal of Biological Chemistry, 268(7), 4989-96, 5 Mar 1993 Abstract
  • Bornstein P, Devarayalu S, Edelhoff S, Disteche C M, Isolation and characterization of the mouse thrombospondin 3 (Thbs3) gene., Genomics, 15(3), 607-13, March 1993 Abstract
  • Slack J L, Liska D J, Bornstein P, Regulation of expression of the type I collagen genes., American Journal of Medical Genetics, 45(2), 140-51, 15 Jan 1993 Abstract
  • Bornstein P, Thrombospondins: structure and regulation of expression [published erratum appears in FASEB J 1993 Jan;7(1):237], Faseb Journal, 6(14), 3290-9, November 1992 Abstract
  • Slack J L, Parker M I, Robinson V R, Bornstein P, Regulation of collagen I gene expression by ras., Molecular and Cellular Biology, 12(10), 4714-23, October 1992 Abstract
  • Vos H L, Devarayalu S, de Vries Y, Bornstein P, Thrombospondin 3 (Thbs3), a new member of the thrombospondin gene family., Journal of Biological Chemistry, 267(17), 12192-6, 15 Jun 1992 Abstract
  • Sherbina N V, Bornstein P, Modulation of thrombospondin gene expression during osteoblast differentiation in MC3T3-E1 cells., Bone, 13(2), 197-201, 1992 Abstract
  • Liska D J, Robinson V R, Bornstein P, Elements in the first intron of the alpha 1(I) collagen gene interact with Sp1 to regulate gene expression., Gene Expression, 2(4), 379-89, 1992 Abstract
  • Fouser L, Sage E H, Clark J, Bornstein P, Feedback regulation of collagen gene expression: a Trojan horse approach., Proceedings of the National Academy of Sciences (USA), 88(22), 10158-62, 15 Nov 1991 Abstract
  • Bornstein P, Devarayalu S, Li P, Disteche C M, Framson P, A second thrombospondin gene in the mouse is similar in organization to thrombospondin 1 but does not respond to serum., Proceedings of the National Academy of Sciences (USA), 88(19), 8636-40, 1 Oct 1991 Abstract
  • Fouser L, Iruela-Arispe L, Bornstein P, Sage E H, Transcriptional activity of the alpha 1(I)-collagen promoter is correlated with the formation of capillary-like structures by endothelial cells in vitro., Journal of Biological Chemistry, 266(27), 18345-51, 25 Sep 1991 Abstract
  • Sage E H, Bornstein P, Extracellular proteins that modulate cell-matrix interactions. SPARC, tenascin, and thrombospondin., Journal of Biological Chemistry, 266(23), 14831-4, 15 Aug 1991 Abstract
  • Bornstein P, O'Rourke K, Wikstrom K, Wolf F W, Katz R, Li P, Dixit V M, A second, expressed thrombospondin gene (Thbs2) exists in the mouse genome., Journal of Biological Chemistry, 266(20), 12821-4, 15 Jul 1991 Abstract
  • Iruela-Arispe M L, Bornstein P, Sage H, Thrombospondin exerts an antiangiogenic effect on cord formation by endothelial cells in vitro., Proceedings of the National Academy of Sciences (USA), 88(11), 5026-30, 1 Jun 1991 Abstract
  • Slack J L, Liska D J, Bornstein P, An upstream regulatory region mediates high-level, tissue-specific expression of the human alpha 1(I) collagen gene in transgenic mice., Molecular and Cellular Biology, 11(4), 2066-74, April 1991 Abstract
  • Maatta A, Bornstein P, Penttinen R P, Highly conserved sequences in the 3'-untranslated region of the COL1A1 gene bind cell-specific nuclear proteins., Febs Letters, 279(1), 9-13, 11 Feb 1991 Abstract
  • Donoviel D B, Amacher S L, Judge K W, Bornstein P, Thrombospondin gene expression is associated with mitogenesis in 3T3 cells: induction by basic fibroblast growth factor., Journal of Cellular Physiology, 145(1), 16-23, October 1990 Abstract
  • Bornstein P, Alfi D, Devarayalu S, Framson P, Li P, Characterization of the mouse thrombospondin gene and evaluation of the role of the first intron in human gene expression., Journal of Biological Chemistry, 265(27), 16691-8, 25 Sep 1990 Abstract
  • Sherwood A L, Bottenus R E, Martzen M R, Bornstein P, Structural and functional analysis of the first intron of the human alpha 2(I) collagen-encoding gene., Gene, 89(2), 239-44, 14 May 1990 Abstract
  • Jaffe E, Bornstein P, Disteche C M, Mapping of the thrombospondin gene to human chromosome 15 and mouse chromosome 2 by in situ hybridization., Genomics, 7(1), 123-6, May 1990 Abstract
  • Liska D J, Slack J L, Bornstein P, A highly conserved intronic sequence is involved in transcriptional regulation of the alpha 1(I) collagen gene., Cell Regulation, 1(6), 487-98, May 1990 Abstract
  • Sherwood A L, Bornstein P, Transcriptional control of the alpha 1(I) collagen gene involves orientation- and position-specific intronic sequences., Biochemical Journal, 265(3), 895-7, 1 Feb 1990 Abstract

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Last Updated: 8/15/2001

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