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In Memoriam
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Alan D. Schreiber
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Department: Medicine
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Contact information
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BRB II/III, Rm. 705
32 421 Curie Blvd.
Philadelphia, PA 19104
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32 421 Curie Blvd.
Philadelphia, PA 19104
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Office: (215) 573-4700
34 Fax: (215) 573-7049
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34 Fax: (215) 573-7049
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Email:
SCHREIBR@MAIL.MED.UPENN.EDU
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SCHREIBR@MAIL.MED.UPENN.EDU
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Publications
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Links
160 Search PubMed for articles
49 Cell and Molecular Biology graduate group faculty webpage.
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160 Search PubMed for articles
49 Cell and Molecular Biology graduate group faculty webpage.
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Education:
21 9 B.A. 14 (Biology) c
2b Rutgers University, 1963.
21 9 M.D. 15 (Medicine) c
3f Albert Einstein College of Medicine,NY, 1967.
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Permanent link21 9 B.A. 14 (Biology) c
2b Rutgers University, 1963.
21 9 M.D. 15 (Medicine) c
3f Albert Einstein College of Medicine,NY, 1967.
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7a Molecular and cell biology of Fc receptors: Mechanisms of function and role in phagocytosis and immune clearance.
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65 Key words: Fc-gamma receptor, phagocytosis, endocytosis, immune clearance, Syk kinase.
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26 Description of Research
281 The Schreiber laboratory has been a major contributor to understanding the molecular and cell biology of Fc-gamma receptors (receptors for immunoglobulin G) in human health and disease. The Fc-gamma receptors are part of the complex immune system that has evolved to enable cells to detect and destroy microbes during infection and antibody coated red blood cells and platelets and immune complexes in autoimmune disorders. Expression of Fc-gamma receptors on the surface of specialized cells such as macrophages enables these cells to ingest antibody-coated particles and bacteria (phagocytosis) and immune complexes (endocytosis).
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2e9 For example, in addition to elucidating basic mechanisms involved in Fc-gamma receptor phagocytosis and endocytosis and the role of the Fc-gamma receptors, the research has demonstrated that the insertion of specific Fc-gamma receptors into non-phagocytic cells enables those cells to mediate phagocytosis and immune clearance. This finding has led to the concept that modification of non-phagocytic cells to express Fc-gamma receptors may enhance the ability of the body to defend itself against infection. Another therapeutic implication is in autoimmune disease. Modifying cells to express Fc-gamma receptors may enhance the clearance of harmful immune complexes from the circulation, thereby preventing their deposit in the tissues.
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1f5 Studies in the Schreiber laboratory have had major implications for understanding the human immune-mediated thrombocytopenic disorders, where activating antibodies directed against the platelet surface can lead to thrombosis. In addition, studies are on-going on the role of Fc-gamma receptors in end stage kidney disease and in alcoholic cirrhosis and the molecular signaling apparatus responsible for such diseases as rheumatoid arthritis, systemic lupus erythematosus and serious infection.
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2e Rotation Projects for 2006-2007
8e 1. Pathways of Fc-gammaRIIA and Fc-gammaRI internalization and association with Syk kinase during phagosome formation and maturation.
69 2. Differences in phagosome fusion and its accompanying calcium signal among Fc-gamma receptors.
40 3. Clearance of IgG coated cells by Fc-gamma receptors.
3d 4. Effect of PECAM-1 on Fc-gamma receptor signaling.
49 5. Role of Cbl and ubiquitination in Fc-gamma receptor function.
83 6. Identification of Fc-gammaRI gamma chain cytoplasmic domain sequences that modulate receptor mediated cytokine release.
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1e Lab personnel:
2d Paul Chien, PhD - Research Specialist
39 Zena K. Indik, PhD - Senior Research Investigator
30 Sharon Hunter, PhD - Research Specialist
2f Moo-Kyung Kim, MD - Research Specialist
2e Xiao-Qing Pan, MD- Research Specialist
2e Zhen-Yu Huang, MD- Research Specialist
30 Brian Jones, BA - Graduate Group Student
31 Randall Worth, PhD - Postdoctoral Student
31 Hesamm Gharavi, MD - Postdoctoral Student
30 Jessica Billet, BA - Research Specialist
2f Tai-Hee Kim-Han, BA- Research Specialist
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Description of Research Expertise
2b Research Interests7a Molecular and cell biology of Fc receptors: Mechanisms of function and role in phagocytosis and immune clearance.
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65 Key words: Fc-gamma receptor, phagocytosis, endocytosis, immune clearance, Syk kinase.
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26 Description of Research
281 The Schreiber laboratory has been a major contributor to understanding the molecular and cell biology of Fc-gamma receptors (receptors for immunoglobulin G) in human health and disease. The Fc-gamma receptors are part of the complex immune system that has evolved to enable cells to detect and destroy microbes during infection and antibody coated red blood cells and platelets and immune complexes in autoimmune disorders. Expression of Fc-gamma receptors on the surface of specialized cells such as macrophages enables these cells to ingest antibody-coated particles and bacteria (phagocytosis) and immune complexes (endocytosis).
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2e9 For example, in addition to elucidating basic mechanisms involved in Fc-gamma receptor phagocytosis and endocytosis and the role of the Fc-gamma receptors, the research has demonstrated that the insertion of specific Fc-gamma receptors into non-phagocytic cells enables those cells to mediate phagocytosis and immune clearance. This finding has led to the concept that modification of non-phagocytic cells to express Fc-gamma receptors may enhance the ability of the body to defend itself against infection. Another therapeutic implication is in autoimmune disease. Modifying cells to express Fc-gamma receptors may enhance the clearance of harmful immune complexes from the circulation, thereby preventing their deposit in the tissues.
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1f5 Studies in the Schreiber laboratory have had major implications for understanding the human immune-mediated thrombocytopenic disorders, where activating antibodies directed against the platelet surface can lead to thrombosis. In addition, studies are on-going on the role of Fc-gamma receptors in end stage kidney disease and in alcoholic cirrhosis and the molecular signaling apparatus responsible for such diseases as rheumatoid arthritis, systemic lupus erythematosus and serious infection.
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2e Rotation Projects for 2006-2007
8e 1. Pathways of Fc-gammaRIIA and Fc-gammaRI internalization and association with Syk kinase during phagosome formation and maturation.
69 2. Differences in phagosome fusion and its accompanying calcium signal among Fc-gamma receptors.
40 3. Clearance of IgG coated cells by Fc-gamma receptors.
3d 4. Effect of PECAM-1 on Fc-gamma receptor signaling.
49 5. Role of Cbl and ubiquitination in Fc-gamma receptor function.
83 6. Identification of Fc-gammaRI gamma chain cytoplasmic domain sequences that modulate receptor mediated cytokine release.
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1e Lab personnel:
2d Paul Chien, PhD - Research Specialist
39 Zena K. Indik, PhD - Senior Research Investigator
30 Sharon Hunter, PhD - Research Specialist
2f Moo-Kyung Kim, MD - Research Specialist
2e Xiao-Qing Pan, MD- Research Specialist
2e Zhen-Yu Huang, MD- Research Specialist
30 Brian Jones, BA - Graduate Group Student
31 Randall Worth, PhD - Postdoctoral Student
31 Hesamm Gharavi, MD - Postdoctoral Student
30 Jessica Billet, BA - Research Specialist
2f Tai-Hee Kim-Han, BA- Research Specialist
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167 Coppolino MG, Dierckman R, Loijens J, Collins RF, Pouladi M, Jongstra-Bilen J, Schreiber AD, Trimble WS, Anderson R, Grinstein S: Inhibition of phosphatidylinositol-4 phosphate 5-kinase la impairs localized actin remodeling and suppresses phagocytosis. J Biol Chem 2002 Notes: in press.
12c Edberg JC, Qin H, Gibson AW, Yee AM, Redecha PB, Indik ZK, Schreiber AD, Kimberly RP: The CY domain in the Fcƒ× Ria a-chain (CD64) alters ƒ×-chain tyrosine-based signaling and phagocytosis. J Biol Chem 2002 Notes: in press.
148 Coppolino MG, King C, Mohtashami M, Schreiber AD, Brumell JH, Finlay BB, Grinsteind S.and Trimble WS: Requirement for N-ethylmaleimide-sensitive factor activity at different stages of bacterial invasion and phagocytosis. J Biol Chem 276: 4772-4780, 2001.
151 Kim M-K, X-Q, Pan, Huang Z-Y, Hunter S, Hwang P-H, Indik ZK and Schreiber AD: Fcƒ× receptors differ in their structural requirements for interaction with the tyrosine kinase Syk in the initial steps of signaling for phagocytosis. Clin. Immunol 98: 125-32, 2001.
109 Worth RG, Mayo-Bond L, van de Winkel JGJ, Todd RF III, Schreiber AD and Petty HR: The cytoplasmic domain of Fcƒ×RIIA (CD32) participates in phagolysosome formation. Blood 98: 3429-34, 2001.
136 Marshall JG, Booth JW, Stambolic V, Mak T, Balla T, Schreiber AD, Meyer T and Grinstein S: Restricted accumulation of phosphatidylinositol3kinase products in a plasmalemmal subdomain during phagocytosis. J. Biol. Chem 153: 1369-80, 2001.
e1 Huang Z-Y, Kim M-K, Indik ZK and Schreiber AD: Fcƒ×RIIA in endocytosis and phagocytosis: Role of ubiquitination during and Cbl. Blood 98: 699a, 2001.
106 Worth RG, Kim M-K and Schreiber AD: The novel Fcƒ×RIIA motif L-T-L provides a specific mechanism for phagolysosome fusion of IgG associated targets. Mol. Biol. of the Cell 12: 202a, 2001.
79 Worth RG, Kim M-K and Schreiber AD: The novel LTL motif of Fcƒ×RIIA 92 enhances phagolysosome fusion when transferred to other receptors. Interen'l Soc. for Exp. Hematol. Tokyo, Japan Aug 2001.
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Selected Publications
103 Booth JW, Kim MK, Jankowski A, Schreiber AD, Grinstein S: Contrasting requirements for ubiquitlylation during Fc receptor-mediated endocytosis and phagocytosis. EMBO J 21: 251-258, 2002.167 Coppolino MG, Dierckman R, Loijens J, Collins RF, Pouladi M, Jongstra-Bilen J, Schreiber AD, Trimble WS, Anderson R, Grinstein S: Inhibition of phosphatidylinositol-4 phosphate 5-kinase la impairs localized actin remodeling and suppresses phagocytosis. J Biol Chem 2002 Notes: in press.
12c Edberg JC, Qin H, Gibson AW, Yee AM, Redecha PB, Indik ZK, Schreiber AD, Kimberly RP: The CY domain in the Fcƒ× Ria a-chain (CD64) alters ƒ×-chain tyrosine-based signaling and phagocytosis. J Biol Chem 2002 Notes: in press.
148 Coppolino MG, King C, Mohtashami M, Schreiber AD, Brumell JH, Finlay BB, Grinsteind S.and Trimble WS: Requirement for N-ethylmaleimide-sensitive factor activity at different stages of bacterial invasion and phagocytosis. J Biol Chem 276: 4772-4780, 2001.
151 Kim M-K, X-Q, Pan, Huang Z-Y, Hunter S, Hwang P-H, Indik ZK and Schreiber AD: Fcƒ× receptors differ in their structural requirements for interaction with the tyrosine kinase Syk in the initial steps of signaling for phagocytosis. Clin. Immunol 98: 125-32, 2001.
109 Worth RG, Mayo-Bond L, van de Winkel JGJ, Todd RF III, Schreiber AD and Petty HR: The cytoplasmic domain of Fcƒ×RIIA (CD32) participates in phagolysosome formation. Blood 98: 3429-34, 2001.
136 Marshall JG, Booth JW, Stambolic V, Mak T, Balla T, Schreiber AD, Meyer T and Grinstein S: Restricted accumulation of phosphatidylinositol3kinase products in a plasmalemmal subdomain during phagocytosis. J. Biol. Chem 153: 1369-80, 2001.
e1 Huang Z-Y, Kim M-K, Indik ZK and Schreiber AD: Fcƒ×RIIA in endocytosis and phagocytosis: Role of ubiquitination during and Cbl. Blood 98: 699a, 2001.
106 Worth RG, Kim M-K and Schreiber AD: The novel Fcƒ×RIIA motif L-T-L provides a specific mechanism for phagolysosome fusion of IgG associated targets. Mol. Biol. of the Cell 12: 202a, 2001.
79 Worth RG, Kim M-K and Schreiber AD: The novel LTL motif of Fcƒ×RIIA 92 enhances phagolysosome fusion when transferred to other receptors. Interen'l Soc. for Exp. Hematol. Tokyo, Japan Aug 2001.
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