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    Sanford Shattil

    TitleDistinguished Professor
    SchoolUniversity of California, San Diego
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      Collapse Overview 
      Collapse Overview
      Research Interests
      Signaling Through Integrin Adhesion Receptors in Development, Vascular Biology and Cancer.

      Integrins represent a ubiquitous family of transmembrane adhesion receptors that transfer biological information between the extracellular and intracellular environments. The general term “integrin signaling” is often used to refer to this process, which is involved in regulating biological events as diverse as embryonic development, synaptic plasticity of the nervous system, innate and adaptive immunity, and the functions of circulating blood cells. Integrin signaling encompasses both “inside-out” signals that regulate integrin affinity and avidity for extracellular ligands and “outside-in” signals that regulate anchorage-dependent cellular responses, such as cell motility and changes in gene expression. Defects in integrin signaling promote certain vascular, inflammatory and neoplastic disorders. The focus of this laboratory is to unravel the molecular basis of integrin signaling as it pertains to development, vascular biology and cancer. In this context, integrin signaling is required for the proliferation and differentiation of stem cells and hematopoietic progenitors into megakaryocytes, for platelet function in hemostasis and thrombosis, for endothelial cell participation in wound healing and angiogenesis, and for tumor progression. Recent work from this laboratory using complementary experimental systems, including human platelets, genetically-modified mice, zebrafish and animal models of neoplasia, indicates that integrin signaling is initiated by their interaction with specific protein kinases, phosphatases and molecular adapters. A current challenge is to integrate the wealth of information obtained from basic research into a complete understanding of integrin signaling, with diagnostic and therapeutic implications for cardiovascular and neoplastic diseases.

      Education and Training
      BA - Psychology, University of Illinois - 1961-1964
      MD - University of Illinois College of Medicine - 1964-1968
      Intern/Resident - Boston City Hospital (Harvard) - 1968-1970
      Fellow - Hematology, Boston City Hospital, Thorndike Lab, Harvard - 1970-1971

      Collapse Research 
      Collapse Research Activities and Funding
      Regulation of Outside-In Integrin Signaling in Platelets
      NIH/NHLBI R01HL087939Apr 1, 2007 - Jan 31, 2008
      Role: Principal Investigator
      Cell Adhesion Mechanisms in Vascular Disease & Thrombosis
      NIH/NHLBI P01HL078784Dec 1, 2004 - Apr 30, 2020
      Role: Co-Investigator
      NIH/NHLBI R01HL065198Aug 1, 2000 - Jul 31, 2006
      Role: Principal Investigator
      Integrin Signaling in Hemostasis and Blood Diseases
      NIH/NHLBI P01HL057900Apr 1, 1997 - Jan 31, 2014
      Role: Principal Investigator
      Discoveries at the Crossroads of Integrin and Inflammatory Signaling in Platelets
      NIH/NHLBI R01HL056595Jul 1, 1996 - May 31, 2021
      Role: Principal Investigator
      NIH/NHLBI R01HL049845Apr 1, 1993 - Mar 31, 1994
      Role: Principal Investigator
      NIH/NHLBI P01HL048728Sep 30, 1992 - Aug 31, 2004
      Role: Co-Investigator
      Regulation of Platelet and Endothelial Cell Function
      NIH P01HL040387Apr 1, 1988 - Apr 30, 2019
      Role: Co-Investigator
      NIH/NHLBI R01HL026523Dec 1, 1980 - Nov 30, 1988
      Role: Principal Investigator
      Hematology Clinical Research Training Program
      NIH/NHLBI T32HL007439Jul 1, 1979 - Jun 30, 2019
      Role: Principal Investigator
      NIH M01RR000833Dec 1, 1977 - Sep 30, 2005
      Role: Co-Investigator

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      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Liao Z, Kasirer-Friede A, Shattil S. Optogenetic interrogation of integrin aVß3 function in endothelial cells. J Cell Sci. 2017 Sep 01. PMID: 28864764.
        View in: PubMed
      2. Shattil S. Blood's 70th anniversary: musings of a Blood editor, 2003-2007. Blood. 2016 Jun 02; 127(22):2649-51. PMID: 27257172.
        View in: PubMed
      3. Ley K, Rivera-Nieves J, Sandborn WJ, Shattil S. Integrin-based therapeutics: biological basis, clinical use and new drugs. Nat Rev Drug Discov. 2016 Mar; 15(3):173-83. PMID: 26822833; PMCID: PMC4890615.
      4. Liao Z, Kato H, Pandey M, Cantor JM, Ablooglu AJ, Ginsberg MH, Shattil S. Interaction of kindlin-2 with integrin ß3 promotes outside-in signaling responses by the aVß3 vitronectin receptor. Blood. 2015 Mar 19; 125(12):1995-2004. PMID: 25587038; PMCID: PMC4366628.
      5. Desgrosellier JS, Lesperance J, Seguin L, Gozo M, Kato S, Franovic A, Yebra M, Shattil S, Cheresh DA. Integrin avß3 drives slug activation and stemness in the pregnant and neoplastic mammary gland. Dev Cell. 2014 Aug 11; 30(3):295-308. PMID: 25117682; PMCID: PMC4147869.
      6. van Sorge NM, Cole JN, Kuipers K, Henningham A, Aziz RK, Kasirer-Friede A, Lin L, Berends ETM, Davies MR, Dougan G, Zhang F, Dahesh S, Shaw L, Gin J, Cunningham M, Merriman JA, Hütter J, Lepenies B, Rooijakkers SHM, Malley R, Walker MJ, Shattil S, Schlievert PM, Choudhury B, Nizet V. The classical lancefield antigen of group a Streptococcus is a virulence determinant with implications for vaccine design. Cell Host Microbe. 2014 Jun 11; 15(6):729-740. PMID: 24922575; PMCID: PMC4078075.
      7. Fitzpatrick P, Shattil S, Ablooglu AJ. C-terminal COOH of integrin ß1 is necessary for ß1 association with the kindlin-2 adapter protein. J Biol Chem. 2014 Apr 18; 289(16):11183-93. PMID: 24599960; PMCID: PMC4036257.
      8. Kasirer-Friede A, Kang J, Kahner B, Ye F, Ginsberg MH, Shattil S. ADAP interactions with talin and kindlin promote platelet integrin aIIbß3 activation and stable fibrinogen binding. Blood. 2014 May 15; 123(20):3156-65. PMID: 24523237; PMCID: PMC4023421.
      9. Ye F, Petrich BG, Anekal P, Lefort CT, Kasirer-Friede A, Shattil S, Ruppert R, Moser M, Fässler R, Ginsberg MH. The mechanism of kindlin-mediated activation of integrin aIIbß3. Curr Biol. 2013 Nov 18; 23(22):2288-95. PMID: 24210614; PMCID: PMC3912999.
      10. Zhao H, Shattil S. Cutaneous thrombosis in PNH. Blood. 2013 Nov 07; 122(19):3249. PMID: 24354009.
        View in: PubMed
      11. Kato H, Liao Z, Mitsios JV, Wang HY, Deryugina EI, Varner JA, Quigley JP, Shattil S. The primacy of ß1 integrin activation in the metastatic cascade. PLoS One. 2012; 7(10):e46576. PMID: 23056350; PMCID: PMC3463578.
      12. Kahner BN, Kato H, Banno A, Ginsberg MH, Shattil S, Ye F. Kindlins, integrin activation and the regulation of talin recruitment to aIIbß3. PLoS One. 2012; 7(3):e34056. PMID: 22457811; PMCID: PMC3311585.
      13. Rangaswami H, Schwappacher R, Marathe N, Zhuang S, Casteel DE, Haas B, Chen Y, Pfeifer A, Kato H, Shattil S, Boss GR, Pilz RB. Cyclic GMP and protein kinase G control a Src-containing mechanosome in osteoblasts. Sci Signal. 2010 Dec 21; 3(153):ra91. PMID: 21177494; PMCID: PMC3093297.
      14. Ablooglu AJ, Tkachenko E, Kang J, Shattil S. Integrin alphaV is necessary for gastrulation movements that regulate vertebrate body asymmetry. Development. 2010 Oct; 137(20):3449-58. PMID: 20843856; PMCID: PMC2947757.
      15. Stoletov K, Kato H, Zardouzian E, Kelber J, Yang J, Shattil S, Klemke R. Visualizing extravasation dynamics of metastatic tumor cells. J Cell Sci. 2010 Jul 01; 123(Pt 13):2332-41. PMID: 20530574; PMCID: PMC2886748.
      16. Shattil S, Kim C, Ginsberg MH. The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol. 2010 Apr; 11(4):288-300. PMID: 20308986; PMCID: PMC3929966.
      17. Kasirer-Friede A, Ruggeri ZM, Shattil S. Role for ADAP in shear flow-induced platelet mechanotransduction. Blood. 2010 Mar 18; 115(11):2274-82. PMID: 19996090; PMCID: PMC2844019.
      18. Desgrosellier JS, Barnes LA, Shields DJ, Huang M, Lau SK, Prévost N, Tarin D, Shattil S, Cheresh DA. An integrin alpha(v)beta(3)-c-Src oncogenic unit promotes anchorage-independence and tumor progression. Nat Med. 2009 Oct; 15(10):1163-9. PMID: 19734908; PMCID: PMC2759406.
      19. Shattil S. The beta3 integrin cytoplasmic tail: protein scaffold and control freak. J Thromb Haemost. 2009 Jul; 7 Suppl 1:210-3. PMID: 19630802.
        View in: PubMed
      20. Lee HS, Lim CJ, Puzon-McLaughlin W, Shattil S, Ginsberg MH. RIAM activates integrins by linking talin to ras GTPase membrane-targeting sequences. J Biol Chem. 2009 Feb 20; 284(8):5119-27. PMID: 19098287; PMCID: PMC2643525.
      21. Ablooglu AJ, Kang J, Petrich BG, Ginsberg MH, Shattil S. Antithrombotic effects of targeting alphaIIbbeta3 signaling in platelets. Blood. 2009 Apr 09; 113(15):3585-92. PMID: 19005179; PMCID: PMC2668853.
      22. Coller BS, Shattil S. The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood. 2008 Oct 15; 112(8):3011-25. PMID: 18840725; PMCID: PMC2569161.
      23. Prévost N, Mitsios JV, Kato H, Burke JE, Dennis EA, Shimizu T, Shattil S. Group IVA cytosolic phospholipase A2 (cPLA2alpha) and integrin alphaIIbbeta3 reinforce each other's functions during alphaIIbbeta3 signaling in platelets. Blood. 2009 Jan 08; 113(2):447-57. PMID: 18840708; PMCID: PMC2615656.
      24. Gutierrez E, Petrich BG, Shattil S, Ginsberg MH, Groisman A, Kasirer-Friede A. Microfluidic devices for studies of shear-dependent platelet adhesion. Lab Chip. 2008 Sep; 8(9):1486-95. PMID: 18818803; PMCID: PMC2683765.
      25. Watanabe N, Bodin L, Pandey M, Krause M, Coughlin S, Boussiotis VA, Ginsberg MH, Shattil S. Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin alphaIIbbeta3. J Cell Biol. 2008 Jun 30; 181(7):1211-22. PMID: 18573917; PMCID: PMC2442211.
      26. Helsten TL, Bunch TA, Kato H, Yamanouchi J, Choi SH, Jannuzi AL, Féral CC, Ginsberg MH, Brower DL, Shattil S. Differences in regulation of Drosophila and vertebrate integrin affinity by talin. Mol Biol Cell. 2008 Aug; 19(8):3589-98. PMID: 18508915; PMCID: PMC2488300.
      27. Hitchcock IS, Fox NE, Prévost N, Sear K, Shattil S, Kaushansky K. Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage specific FAK knockout. Blood. 2008 Jan 15; 111(2):596-604. PMID: 17925492; PMCID: PMC2200856.
      28. Kasirer-Friede A, Kahn ML, Shattil S. Platelet integrins and immunoreceptors. Immunol Rev. 2007 Aug; 218:247-64. PMID: 17624957.
        View in: PubMed
      29. Ablooglu AJ, Kang J, Handin RI, Traver D, Shattil S. The zebrafish vitronectin receptor: characterization of integrin alphaV and beta3 expression patterns in early vertebrate development. Dev Dyn. 2007 Aug; 236(8):2268-76. PMID: 17626277.
        View in: PubMed
      30. Petrich BG, Fogelstrand P, Partridge AW, Yousefi N, Ablooglu AJ, Shattil S, Ginsberg MH. The antithrombotic potential of selective blockade of talin-dependent integrin alpha IIb beta 3 (platelet GPIIb-IIIa) activation. J Clin Invest. 2007 Aug; 117(8):2250-9. PMID: 17627302; PMCID: PMC1906732.
      31. Prévost N, Kato H, Bodin L, Shattil S. Platelet integrin adhesive functions and signaling. Methods Enzymol. 2007; 426:103-15. PMID: 17697882.
        View in: PubMed
      32. Kaushansky K, Shattil S. Bloodlines: the importance of mentoring for the future of hematology. Blood. 2007 Feb 15; 109(4):1353-4. PMID: 17047145.
        View in: PubMed
      33. Kasirer-Friede A, Moran B, Nagrampa-Orje J, Swanson K, Ruggeri ZM, Schraven B, Neel BG, Koretzky G, Shattil S. ADAP is required for normal alphaIIbbeta3 activation by VWF/GP Ib-IX-V and other agonists. Blood. 2007 Feb 01; 109(3):1018-25. PMID: 17003372; PMCID: PMC1785130.
      34. Han J, Lim CJ, Watanabe N, Soriani A, Ratnikov B, Calderwood DA, Puzon-McLaughlin W, Lafuente EM, Boussiotis VA, Shattil S, Ginsberg MH. Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3. Curr Biol. 2006 Sep 19; 16(18):1796-806. PMID: 16979556.
        View in: PubMed
      35. Abtahian F, Bezman N, Clemens R, Sebzda E, Cheng L, Shattil S, Kahn ML, Koretzky GA. Evidence for the requirement of ITAM domains but not SLP-76/Gads interaction for integrin signaling in hematopoietic cells. Mol Cell Biol. 2006 Sep; 26(18):6936-49. PMID: 16943434; PMCID: PMC1592869.
      36. Bunch TA, Helsten TL, Kendall TL, Shirahatti N, Mahadevan D, Shattil S, Brower DL. Amino acid changes in Drosophila alphaPS2betaPS integrins that affect ligand affinity. J Biol Chem. 2006 Feb 24; 281(8):5050-7. PMID: 16371365.
        View in: PubMed
      37. Ginsberg MH, Partridge A, Shattil S. Integrin regulation. Curr Opin Cell Biol. 2005 Oct; 17(5):509-16. PMID: 16099636.
        View in: PubMed
      38. Arias-Salgado EG, Haj F, Dubois C, Moran B, Kasirer-Friede A, Furie BC, Furie B, Neel BG, Shattil S. PTP-1B is an essential positive regulator of platelet integrin signaling. J Cell Biol. 2005 Aug 29; 170(5):837-45. PMID: 16115959; PMCID: PMC2171339.
      39. Shattil S. Integrins and Src: dynamic duo of adhesion signaling. Trends Cell Biol. 2005 Aug; 15(8):399-403. PMID: 16005629.
        View in: PubMed
      40. Arias-Salgado EG, Lizano S, Shattil S, Ginsberg MH. Specification of the direction of adhesive signaling by the integrin beta cytoplasmic domain. J Biol Chem. 2005 Aug 19; 280(33):29699-707. PMID: 15937333.
        View in: PubMed
      41. George JN, Shattil S. Letter to authors and readers regarding the new NIH policy on public access. Blood. 2005 May 15; 105(10):3767. PMID: 15817680.
        View in: PubMed
      42. Buensuceso CS, Obergfell A, Soriani A, Eto K, Kiosses WB, Arias-Salgado EG, Kawakami T, Shattil S. Regulation of outside-in signaling in platelets by integrin-associated protein kinase C beta. J Biol Chem. 2005 Jan 07; 280(1):644-53. PMID: 15536078.
        View in: PubMed
      43. Buensuceso CS, Arias-Salgado EG, Shattil S. Protein-protein interactions in platelet alphaIIbbeta3 signaling. Semin Thromb Hemost. 2004 Aug; 30(4):427-39. PMID: 15354264.
        View in: PubMed
      44. Shattil S, Newman PJ. Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood. 2004 Sep 15; 104(6):1606-15. PMID: 15205259.
        View in: PubMed
      45. de Virgilio M, Kiosses WB, Shattil S. Proximal, selective, and dynamic interactions between integrin alphaIIbbeta3 and protein tyrosine kinases in living cells. J Cell Biol. 2004 May 10; 165(3):305-11. PMID: 15123737; PMCID: PMC2172182.
      46. Shattil S. Open access, yes! Open excess, no! Blood. 2004 May 01; 103(9):3257. PMID: 15096439.
        View in: PubMed
      47. Kerrigan SW, Gaur M, Murphy RP, Shattil S, Leavitt AD. Caspase-12: a developmental link between G-protein-coupled receptors and integrin alphaIIbbeta3 activation. Blood. 2004 Sep 01; 104(5):1327-34. PMID: 15059849.
        View in: PubMed
      48. Kasirer-Friede A, Cozzi MR, Mazzucato M, De Marco L, Ruggeri ZM, Shattil S. Signaling through GP Ib-IX-V activates alpha IIb beta 3 independently of other receptors. Blood. 2004 May 01; 103(9):3403-11. PMID: 14726383.
        View in: PubMed
      49. Arias-Salgado EG, Lizano S, Sarkar S, Brugge JS, Ginsberg MH, Shattil S. Src kinase activation by direct interaction with the integrin beta cytoplasmic domain. Proc Natl Acad Sci U S A. 2003 Nov 11; 100(23):13298-302. PMID: 14593208; PMCID: PMC263791.
      50. Tadokoro S, Shattil S, Eto K, Tai V, Liddington RC, de Pereda JM, Ginsberg MH, Calderwood DA. Talin binding to integrin beta tails: a final common step in integrin activation. Science. 2003 Oct 03; 302(5642):103-6. PMID: 14526080.
        View in: PubMed
      51. Shattil S. A (blood) smear campaign. Blood. 2003 Apr 01; 101(7):2453. PMID: 12642341.
        View in: PubMed
      52. Buensuceso C, de Virgilio M, Shattil S. Detection of integrin alpha IIbbeta 3 clustering in living cells. J Biol Chem. 2003 Apr 25; 278(17):15217-24. PMID: 12595537.
        View in: PubMed
      53. Eto K, Leavitt AL, Nakano T, Shattil S. Development and analysis of megakaryocytes from murine embryonic stem cells. Methods Enzymol. 2003; 365:142-58. PMID: 14696343.
        View in: PubMed
      54. Eto K, Murphy R, Kerrigan SW, Bertoni A, Stuhlmann H, Nakano T, Leavitt AD, Shattil S. Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling. Proc Natl Acad Sci U S A. 2002 Oct 01; 99(20):12819-24. PMID: 12239348; PMCID: PMC130543.
      55. Woodside DG, Obergfell A, Talapatra A, Calderwood DA, Shattil S, Ginsberg MH. The N-terminal SH2 domains of Syk and ZAP-70 mediate phosphotyrosine-independent binding to integrin beta cytoplasmic domains. J Biol Chem. 2002 Oct 18; 277(42):39401-8. PMID: 12171941.
        View in: PubMed
      56. Bertoni A, Tadokoro S, Eto K, Pampori N, Parise LV, White GC, Shattil S. Relationships between Rap1b, affinity modulation of integrin alpha IIbbeta 3, and the actin cytoskeleton. J Biol Chem. 2002 Jul 12; 277(28):25715-21. PMID: 11994301.
        View in: PubMed
      57. Obergfell A, Eto K, Mocsai A, Buensuceso C, Moores SL, Brugge JS, Lowell CA, Shattil S. Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton. J Cell Biol. 2002 Apr 15; 157(2):265-75. PMID: 11940607; PMCID: PMC2199242.
      58. Kasirer-Friede A, Ware J, Leng L, Marchese P, Ruggeri ZM, Shattil S. Lateral clustering of platelet GP Ib-IX complexes leads to up-regulation of the adhesive function of integrin alpha IIbbeta 3. J Biol Chem. 2002 Apr 05; 277(14):11949-56. PMID: 11812775.
        View in: PubMed