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    Caterina Strambio De Castillia PhD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    373 Plantation Street, Biotech II, Suite 114
    Worcester MA 01605
    Phone508-856-2383
        Biography 
        awards and honors
        Italian Society for Molecular Biology and Biophysis1988Best Annual Experimental Thesis Award
        Councily for the International Exchange of Scholars, United States Department of State1989Fullbright Scholar Program Fellowship
        Italian Foreign Ministry1995Pre-doctoral Fellowship for Promising young Italian investigator studying abroad
        Overview 
        Narrative

        Academic Background

        Caterina Strambio De Castillia grew up in Italy and received her Laurea in Biologia (equivalent to B.S./M.S.) from the University of Pavia in 1988. She obtained her Ph.D. (1992-1998) working with Gunter Blobel at The Rockefeller University, where she investigated the manner in which the nuclear pore complex interfaces with the cellular genome in yeast. She continued this work at the same institution in the laboratory of Mike Rout, initially as a postdoctoral fellow (1998-2002) and then as a Research Associate (2002-2006). She then moved to the IRB-Bellinzona and to the University of Geneva, Switzerland, where she was a staff Research Scientist (2006-2012) developing imaging and proteomics methods to study the mechanism by which HIV-1 interacts with the host defense mechanisms to gain access to the cell nucleus. Her work has been supported by the American Cancer Society, the European Union and the Swiss National Science Foundation. In 2012, Dr. Strambio De Castillia joined the Program in Molecular Medicine at the University of Massachusetts Medical School.


        Dissecting the interplay between HIV-1 and human cells during viral entry

        After HIV-1 fuses with a target cell membrane, the virion core is delivered into the cytosol of the infected cell. A DNA copy (cDNA) of the HIV-1 RNA genome is produced by the HIV-1 reverse transcriptase (RT) and the cDNA is ligated to host cell chromosomal DNA by HIV-1 integrase. Despite 30 years of research, detailed understanding of these essential early steps in HIV-1 replication remains elusive. Some of the open questions ask:

        1. Does the virion core need to undergo an “uncoating” process to enable reverse transcription?

        2. Is RT active in the cytoplasm or the nucleus?

        3. Does the intracellular path followed by the virion core influence its ability to give rise to a productive infection?

        4. How does HIV-1 reach the nucleus?

        Up to this point, progress has been impeded by the fragile nature of HIV-1 replication intermediates and the low infectivity-to-particle ratio of virions, which makes it difficult if not impossible to meaningfully dissect different steps in the pathway by bulk biochemical means alone.


        Tracking HIV-1 as it traverses living cells in real-time

        The goal of the Strambio De Castillia laboratory is to remedy this lack of understanding by developing methods to label and track infectious HIV-1 as it traverses living cells in real-time. The aim is to identify thoserare particles that have successfully integrated into chromosomal DNA, retrace their intracellular path as they travel to reach the cellular genome and identify their intracellular interaction partners, in a time and space resolved manner. Such information will be invaluable for furthering our understanding of the initial steps in the HIV-1 life cycle and for the rational design of anti-HIV-1 drugs that target them.


        Quantitative analysis of viral trajectories gives insight about viral-host interactions

        Using dynamic imaging followed by rigorous computational analysis of viral particle trajectories, the complex interplay between HIV-1 and cellular components can be solved.  A major hurdle, has been the difficulty of keeping track of multiple moving viral particles with sufficient temporal and spatial resolution while at the same time probing multiple experimental contexts.


        A three-pronged multidisciplinary approach

        In order to meet this challenge, the Strambio De Castillia group is engaged in a multidisciplinary, collaborative effort aimed at developing integrated workflows that will provide the analysis, data management and visualization capabilities required to drive a more complete understanding of viral-host interactions in the context of living human tissues. The project articulates on three fronts:

        1. Real-time recording of HIV-1 viral core movement in infected human cells.

        2. Viral particle tracking and motion analysis.

        3. Building a novel bio-image informatics framework, called OMEGA, to support the comprehensive examination of particle movement across multiple experimental models and conditions.


        OMEGA project website

        More information on the OMEGA project can be found following this link: http://omega.umassmed.edu/








        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Niepel M, Molloy KR, Williams R, Farr JC, Meinema AC, Vecchietti N, Cristea IM, Chait BT, Rout MP, Strambio-De-Castillia C. The nuclear basket proteins Mlp1p and Mlp2p are part of a dynamic interactome including Esc1p and the proteasome. Mol Biol Cell. 2013 Dec; 24(24):3920-38.
          View in: PubMed
        2. Xu H, Franks T, Gibson G, Huber K, Rahm N, De Castillia CS, Luban J, Aiken C, Watkins S, Sluis-Cremer N, Ambrose Z. Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Retrovirology. 2013; 10:70.
          View in: PubMed
        3. Strambio-De-Castilla C. Jumping over the fence: RNA nuclear export revisited. Nucleus. 2013 Mar-Apr; 4(2):95-9.
          View in: PubMed
        4. Vecchietti, N., N. Storelli, S. Peduzzi, P. Barbieri, C. Strambio-de-Castillia, and M. Tonolla. Gli aggregati sintrofici di Thiodictyon syntrophicum CAD16 e Desulfocapsa thiozymogenes CAD626 del lago di Cadagno. Bollettino della Societa' Ticinese di Scienze Naturali. 2012; 100:107 - 119.
        5. Pertel T, Hausmann S, Morger D, Züger S, Guerra J, Lascano J, Reinhard C, Santoni FA, Uchil PD, Chatel L, Bisiaux A, Albert ML, Strambio-De-Castillia C, Mothes W, Pizzato M, Grütter MG, Luban J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature. 2011 Apr 21; 472(7343):361-5.
          View in: PubMed
        6. Strambio-De-Castillia C, Niepel M, Rout MP. The nuclear pore complex: bridging nuclear transport and gene regulation. Nat Rev Mol Cell Biol. 2010 Jul; 11(7):490-501.
          View in: PubMed
        7. Sokolskaja E, Olivari S, Zufferey M, Strambio-De-Castillia C, Pizzato M, Luban J. Cyclosporine blocks incorporation of HIV-1 envelope glycoprotein into virions. J Virol. 2010 May; 84(9):4851-5.
          View in: PubMed
        8. Neagu MR, Ziegler P, Pertel T, Strambio-De-Castillia C, Grütter C, Martinetti G, Mazzucchelli L, Grütter M, Manz MG, Luban J. Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components. J Clin Invest. 2009 Oct; 119(10):3035-47.
          View in: PubMed
        9. Sebastian S, Grütter C, Strambio de Castillia C, Pertel T, Olivari S, Grütter MG, Luban J. An invariant surface patch on the TRIM5alpha PRYSPRY domain is required for retroviral restriction but dispensable for capsid binding. J Virol. 2009 Apr; 83(7):3365-73.
          View in: PubMed
        10. Strambio-de-Castillia C, Tetenbaum-Novatt J, Imai BS, Chait BT, Rout MP. A method for the rapid and efficient elution of native affinity-purified protein A tagged complexes. J Proteome Res. 2005 Nov-Dec; 4(6):2250-6.
          View in: PubMed
        11. Niepel M, Strambio-de-Castillia C, Fasolo J, Chait BT, Rout MP. The nuclear pore complex-associated protein, Mlp2p, binds to the yeast spindle pole body and promotes its efficient assembly. J Cell Biol. 2005 Jul 18; 170(2):225-35.
          View in: PubMed
        12. Strambio-de-Castillia C, Rout MP. The structure and composition of the yeast NPC. Results Probl Cell Differ. 2002; 35:1-23.
          View in: PubMed
        13. Kipper J, Strambio-de-Castillia C, Suprapto A, Rout MP. Isolation of nuclear envelope from Saccharomyces cerevisiae. Methods Enzymol. 2002; 351:394-408.
          View in: PubMed
        14. Rout M.P. and C. Strambio-De-Castillia. Isolation of Yeast Nuclear Pore Complex and Nuclear Envelopes. INSERM Atelier de Formation/INSERM Worshops. 2000; 121:23-24.
        15. Strambio de Castillia C, Rout MP. TAPping into transport. Nat Cell Biol. 1999 Jun; 1(2):E31-3.
          View in: PubMed
        16. Strambio-de-Castillia C, Blobel G, Rout MP. Proteins connecting the nuclear pore complex with the nuclear interior. J Cell Biol. 1999 Mar 8; 144(5):839-55.
          View in: PubMed
        17. Hurwitz ME, Strambio-de-Castillia C, Blobel G. Two yeast nuclear pore complex proteins involved in mRNA export form a cytoplasmically oriented subcomplex. Proc Natl Acad Sci U S A. 1998 Sep 15; 95(19):11241-5.
          View in: PubMed
        18. Strambio-De-Castillia C. Identification and characterization of Mlp1 and Mlp2: Molecular components of filaments localized at the interface between the nuclear pore complex and the nuclear interior. 1998.
        19. Rout M.P. and C. Strambio-De-Castillia. Isolation of Yeast Nuclear Pore Complex and Nuclear Envelopes. Cell Biology a Laboratory Handbook, J. E. Celis. 1998; 2:143-151.
        20. Strambio-de-Castillia C, Blobel G, Rout MP. Isolation and characterization of nuclear envelopes from the yeast Saccharomyces. J Cell Biol. 1995 Oct; 131(1):19-31.
          View in: PubMed
        21. Kraemer DM, Strambio-de-Castillia C, Blobel G, Rout MP. The essential yeast nucleoporin NUP159 is located on the cytoplasmic side of the nuclear pore complex and serves in karyopherin-mediated binding of transport substrate. J Biol Chem. 1995 Aug 11; 270(32):19017-21.
          View in: PubMed
        22. Strambio-de-Castillia C, Hunter E. Mutational analysis of the major homology region of Mason-Pfizer monkey virus by use of saturation mutagenesis. J Virol. 1992 Dec; 66(12):7021-32.
          View in: PubMed
        23. Strambio-De-Castillia C. Presence of Transcriptional Elements in Putative Human Replication Origins. 1988.
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