Contact Information

Arnaout Laboratory

CNY 149-8
149 13th Street
Charlestown, MA  02129

Phone: 617-726-5663
Fax: 617-726-5671

Email: aarnaout1@mgh.harvard.edu
Hours: Monday–Friday, 8:00 am–6:00 pm

Grants Manager: Diane DeAngelis
Phone: 617-724-1551
Email: ddeangelis2@mgh.harvard.edu

Laboratory Manager: Zhiping Ding
Phone: 617-724-9875
Email: zding@partners.org

Explore This Research Lab

    About the Lab

    A major research goal of the Arnaout Laboratory is to elucidate the structure and function of integrins, cell adhesion receptors that play vital roles in normal physiology and disease and use the derived information in structure-based design of new and safer anti-integrin drugs targeting heart disease, fibrosis, and cancer.

    Other research interests include elucidating mechanisms underlying cyst formation in Autosomal Dominant Polycystic Kidney Disease, transcriptional regulation of hematopoiesis, mechanisms of kidney regeneration, and design of microfluidic dialysis devices.

    Research Projects

    • Atomic structure of the integrin aVb3 in complex with macromolecular ligands
    • Structure-based design of novel anti-integrin therapeutics
    • EM structure of the leukocyte integrin CD11b/CD18 (aMb2)
    • Role of adaptor proteins in regulation of leukocyte integrins
    • Role of integrins in ischemia-reperfusion injury models
    • Mechanisms of cyst formation in Autosomal Dominant Polycystic Kidney Disease
    • Mechanisms of renal injury and regeneration
    • Development of microfluidic devices for dialysis
    • Transcriptional regulation of hematopoiesis
    Crystal structure of the A-type domain from integrin CD11b. Cell 1993;72:287, Cell, 1995;80:631
    A ribbon drawing of the crystallized extracellular segment of alpha-V beta-3. The alpha-V and beta-3 subunits appear in blue and yellow, respectively. The structure is severely bent at the kneelike "genu" (arrows). Disordered regions are in gray. At right is a computer model of the straightened alpha-V beta-3, which was developed by extension (135 degrees) and rotation (120 degrees) of the bent structure at the genu. The approximate location and shape of three small and disordered domains are shown in gray. Science, 294:339, 2001
    Surface representation of the ligand-binding site in an integrin heterodimer (a subunit is in blue; b subunit is in red) . The ligand is an Arg-Gly-Asp containing peptide, shown as ball-and stick model. Two metal ions are shown in cyan and magenta. Science, 296:151, 2002
    Ribbon diagram of a hypothetical model showing an inactive (left) and an active (right) conformations of the aA-integrin CD11b/CD18. Current Biology, 12:R340, 2002
     
    Pseudoatomic models of unliganded (A) and fibronectin-bound (B) integrin aVb3. aV is in blue and b3 in red. Fn-9 and 10 are in green and yellow, respectively. J Cell Biol 168:1109, 2005
    (a, b) Loss of the transcription factor ZBP-89 results in a bloodless phenotype in zebrafish. (a, b) DAF staining of 48 hpf whole-mount zebrafish embryos. Blood (arrows) is present in axial vessels and heart (short arrow) in wild-type (a) but not ZBP-89 morphant (b) embryos. Views are lateral with anterior to the left and dorsal to the top. (c, d) Overexpression of ZBP-89 impairs angiogenesis. In situ hybridization of wild-type embryos (c) or wild-type embryos overexpressing ZBP-89 (d) reveals a marked reduction in intersomitic expression of the endothelial markers flk1 (d), when compared with the respective wild-type embryos. Development, 133:364, 2006
    Ribbon diagram showing two views of a structure model of the complete aVb3 ectodomain plus the TM domains. The orientation of the ectodomain relative to the TM domains, show that the ligand binding site is accessible to macromolecular ligands without unbending. The a-genu and propeller metal ions are in orange. J Cell Biol, 186: 589, 2009

    Research Positions

    If you are interested in applying for a postdoctoral position, or are a Harvard PhD student interested in a laboratory rotation, please e-mail your CV (for student and postdoctoral) and reference letters (for postdoctoral) to: aarnaout1@mgh.harvard.edu

    Publications

    See a list of publications from this investigator.

    News Articles

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