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Alan
D. Schreiber
Professor, Dept of Medicine (Hematology/Oncology)
Cell
Biology and Physiology Program
Address
705
Biomedical Rsch Bldg II/III (Office)
736 Biomedical Rsch Bldg II/III (Lab)
421 Curie Blvd
Philadelphia, PA 19104-4318
Office tel.: 215 573-4700
Lab tel.: 215 573-4701
Fax: 215 573-7049
E-mail: schreibr@mail.med.upenn.edu
EDUCATION
Rutgers University: BA (Biology), 1963.
Albert Einstein College of Medicine: MD (Medicine), 1967.
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RESEARCH
INTERESTS
- Molecular and cell biology of Fc receptors: Mechanisms
of function and role in phagocytosis and immune clearance.
Key
words: Fc-gamma receptor, phagocytosis,
endocytosis, immune clearance, Syk kinase.
Search PubMed for articles
DESCRIPTION
OF RESEARCH
The Schreiber laboratory has been a major contributor to
understanding the molecular and cell biology of Fcγ receptors
(receptors for immunoglobulin G) in human health and disease.
The Fcγ 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
Fcγ 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).
For example, in addition to elucidating basic mechanisms
involved in Fcγ receptor phagocytosis and endocytosis
and the role of the Fcγ receptors, the research has demonstrated
that the insertion of specific Fcγ 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 Fcγ receptors may
enhance the ability of the body to defend itself against infection.
Another therapeutic implication is in autoimmune disease.
Modifying cells to express Fcγ receptors may enhance
the clearance of harmful immune complexes from the circulation,
thereby preventing their deposit in the tissues.
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 Fcγ 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.
RECENT
PUBLICATIONS
Albelda SM. Lau KC, Chien P, Huang Z-Y, Arguiris E, Bohen
A, Sun J, Billet JA, Christofidou-Solomidou M, Indik ZK, Schreiber
AD. Role for platelet-endothelial cell adhesion molecule-1
(PECAM) in macrophage Fcγ receptor function. Am J
Respir Cell Mol Biol. 312:246-255, 2004.
Huang ZY, Hunter S, Kim MK, Indik ZK, and Schreiber AD. The
effect of phosphatases SHP-1 and SHIP-1 on signaling by the
ITIM- and ITAM-containing Fcγ receptors FcgammaRIIB and
FcgammaRIIA. J Leukoc Biol. 73:823-829. 2003.
Worth RG, Kim MK, Kindzelskii AL, Petty HR, and Schreiber
AD. Signal sequence within Fc gamma RIIA controls calcium
wave propagation patterns: apparent role in phagolysosome
fusion. Proc Natl Acad Sci U S A. 100:4533-4538.
2003.
Ulanova M, Puttagunta L, Kim MK, Schreiber AD, Befus AD.
Antisense oligonucleotides to Syk kinase: a novel therapeutic
approach for respiratory disorders. Curr Opin Investig
Drugs. 4:552-555, 2003.
Booth JW, Kim MK, Jankowski A, Schreiber AD, and Grinstein
S. Contrasting requirements for ubiquitylation during Fc receptor-mediated
endocytosis and phagocytosis. EMBO J. 21:251-258,
2002.
Lab
ROTATION
PROJECTS FOR 2006-2007
- Pathways of FcγRIIA and FcγRI internalization
and association with Syk kinase during phagosome formation
and maturation.
- Differences in phagosome fusion and its accompanying calcium
signal among Fcγ receptors.
- Clearance of IgG coated cells by Fcγ receptors.
- Effect of PECAM-1 on Fcγ receptor signaling.
- Role of Cbl and ubiquitination in Fcγ receptor function.
- Identification of FcγRI α chain cytoplasmic domain
sequences that modulate receptor mediated cytokine release.
- Lab
personnel:
- Paul Chien, PhD - Research Specialist
Zena K. Indik, PhD - Senior Research Investigator
Sharon Hunter, PhD - Research Specialist
Moo-Kyung Kim, MD - Research Specialist
Xiao-Qing Pan, MD - Research Specialist
Zhen-Yu Huang, MD - Research Specialist
Randall Worth, PhD - Postdoctoral Student
Daniel Barreda, PhD - Postdoctoral Student
Jessica Billet, BA - Research Specialist
Tai-Hee Kim-Han, BA- Research Specialist
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last updated 7/2004
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