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Caterina Strambio De Castillia PhD

TitleAssistant Professor
InstitutionUMass Chan Medical School
DepartmentProgram in Molecular Medicine
AddressUMass Chan Medical School
373 Plantation Street Two Biotech Suite 114
Worcester MA 01605
Phone508-856-2383
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentProgram in Molecular Medicine


    Collapse Biography 
    Collapse education and training
    University of Pavia, Pavia, PV, ItalyBSBiological Sciences
    The Rockefeller University, New York, NY, United StatesPHDCell Biology
    Collapse awards and honors
    1988Best Annual Experimental Thesis Award, Italian Society for Molecular Biology and Biophysis
    1989Fullbright Scholar Program Fellowship, Councily for the International Exchange of Scholars, United States Department of State
    1995Pre-doctoral Fellowship for Promising young Italian investigator studying abroad, Italian Foreign Ministry

    Collapse Overview 
    Collapse overview

    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://big.umassmed.edu/omegaweb/

     

     

     

     

     



    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Rigano A, Galli V, Clark JM, Pereira LE, Grossi L, Luban J, Giulietti R, Leidi T, Hunter E, Valle M, Sbalzarini IF, Strambio-De-Castillia C. OMEGA: a software tool for the management, analysis, and dissemination of intracellular trafficking data that incorporates motion type classification and quality control. DOI: 10.1101/251850. bioRxiv.org . 2018. View Publication.
    2. Rigano A, Strambio De Castillia C. Proposal for minimum information guidelines to report and reproduce results of particle tracking and motion analysis. bioRxiv. 2017 July 13; available at: https://doi.org/10.1101/155036; DOI: 10.1101/155036. Proposal for minimum information guidelines to report and reproduce results of particle tracking and motion analysis. DOI: 10.1101/155036. bioRxiv.org. 2017. View Publication.
    3. Alghanem B, Nikitin F, Stricker T, Duchoslav E, Luban J, Strambio-De-Castillia C, Muller M, Lisacek F, Varesio E, Hopfgartner G. Optimization by infusion of multiple reaction monitoring transitions for sensitive quantification of peptides by liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom. 2017 May 15; 31(9):753-761. PMID: 28199054.
      Citations:    Fields:    Translation:HumansCells
    4. Alessandro Rigano and Caterina Strambio De Castillia. Open Microscopy Environment inteGrated Analysis project: code repository. Version v20170504 (beta v034). GitHub. 2017. View Publication.
    5. Caterina Strambio De Castillia, Vanni Galli, Jasmine Clark, Andrea Danani, Raffaello Giulietti, Loris Grossi, Eric Hunter, Jeremy Luban, Massimo Maiolo, Lara E. Pereira, Alessandro Rigano, Bernd Rinn, Mario Valle . OMEGA: viral particle tracking work- and data-flows for images stored in OMERO. F1000Research 2016, 5:1560 (slides) (doi: 10.7490/f1000research.1112460.1). [Presented at 1st Annual OMERO in Action Meeting (2011)-51 slides]. 2016. View Publication.
    6. Rigano, A. & Strambio-De-Castillia, C. OMEGA: an open source environment to facilitate the analysis of intra-cellular motion, the estimation of error and the reproducibility and dissemination of analysis results. F1000Research 2016, 5:1403 (slides) (doi: 10.7490/f1000research.1112347.1). [Presented at 10th Annual OME User Meeting (2015)-12 slides]. 2016. View Publication.
    7. Alessandro Rigano, Vanni Galli, Raffaello Giulietti, Tiziano Leidi, Mario Valle, Ivo Sbalzarini, Caterina Strambio De Castillia. OMEGA: an open source environment to facilitate the execution of motion analysis workflows, to estimate error and to share results. F1000Research 2016, 5:1392 (poster) (doi:10.7490/f1000research.1112339.1). [Presented at 10th Annual OME User Meeting (2015)-poster]. 2016. View Publication.
    8. Caterina Strambio De Castillia and Alessandro Rigano. Minimum Information About Particle Tracking Experiments. Minimum Information Metadata Standard. Available at: https://biosharing.org/bsg-s000671 . 2016. View Publication.
    9. Bilbao A, Zhang Y, Varesio E, Luban J, Strambio-De-Castillia C, Lisacek F, Hopfgartner G. Ranking Fragment Ions Based on Outlier Detection for Improved Label-Free Quantification in Data-Independent Acquisition LC-MS/MS. J Proteome Res. 2015 Nov 06; 14(11):4581-93. PMID: 26412574.
      Citations: 5     Fields:    Translation:HumansCells
    10. Zhang Y, Bilbao A, Bruderer T, Luban J, Strambio-De-Castillia C, Lisacek F, Hopfgartner G, Varesio E. The Use of Variable Q1 Isolation Windows Improves Selectivity in LC-SWATH-MS Acquisition. J Proteome Res. 2015 Oct 02; 14(10):4359-71. PMID: 26302369.
      Citations: 41     Fields:    Translation:HumansCells
    11. Zhang Y, Bottinelli D, Lisacek F, Luban J, Strambio-De-Castillia C, Varesio E, Hopfgartner G. Optimization of human dendritic cell sample preparation for mass spectrometry-based proteomic studies. Anal Biochem. 2015 Sep 01; 484:40-50. PMID: 25983236.
      Citations: 6     Fields:    Translation:HumansCells
    12. Bilbao A, Varesio E, Luban J, Strambio-De-Castillia C, Hopfgartner G, Müller M, Lisacek F. Processing strategies and software solutions for data-independent acquisition in mass spectrometry. Proteomics. 2015 Mar; 15(5-6):964-80. PMID: 25430050.
      Citations: 43     Fields:    
    13. 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. PMID: 24152732.
      Citations: 57     Fields:    Translation:AnimalsCells
    14. Xu H, Franks T, Gibson G, Huber K, Rahm N, Strambio De Castillia C, 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 Jul 09; 10:70. PMID: 23835323.
      Citations: 50     Fields:    Translation:HumansCells
    15. Strambio-De-Castilla C. Jumping over the fence: RNA nuclear export revisited. Nucleus. 2013 Mar-Apr; 4(2):95-9. PMID: 23528257.
      Citations: 3     Fields:    Translation:HumansCells
    16. 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. View Publication.
    17. Tarkowski M, Ferraris L, Martone S, Strambio de Castillia F, Misciagna D, Mazzucchelli RI, Lattuada E, Paraninfo G, Galli M, Riva A. Expression of interleukin-15 and interleukin-15R? in monocytes of HIV type 1-infected patients with different courses of disease progression. AIDS Res Hum Retroviruses. 2012 Jul; 28(7):693-701. PMID: 21902580.
      Citations: 4     Fields:    Translation:HumansCells
    18. 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. PMID: 21512573.
      Citations: 332     Fields:    Translation:HumansCells
    19. 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. PMID: 20571586.
      Citations: 228     Fields:    Translation:HumansAnimalsCells
    20. 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. PMID: 20181694.
      Citations: 8     Fields:    Translation:HumansCells
    21. 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. PMID: 19741300.
      Citations: 74     Fields:    Translation:HumansAnimalsCells
    22. 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. PMID: 19153241.
      Citations: 20     Fields:    Translation:HumansCells
    23. 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. PMID: 16335973.
      Citations: 10     Fields:    Translation:Cells
    24. 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. PMID: 16027220.
      Citations: 54     Fields:    Translation:AnimalsCells
    25. Kipper J, Strambio-de-Castillia C, Suprapto A, Rout MP. Isolation of nuclear envelope from Saccharomyces cerevisiae. Methods Enzymol. 2002; 351:394-408. PMID: 12073359.
      Citations: 6     Fields:    Translation:AnimalsCells
    26. Strambio-de-Castillia C, Rout MP. The structure and composition of the yeast NPC. Results Probl Cell Differ. 2002; 35:1-23. PMID: 11791402.
      Citations: 1     Fields:    Translation:AnimalsCells
    27. 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.
    28. Strambio de Castillia C, Rout MP. TAPping into transport. Nat Cell Biol. 1999 Jun; 1(2):E31-3. PMID: 10559889.
      Citations: 1     Fields:    Translation:HumansAnimalsCells
    29. Strambio-de-Castillia C, Blobel G, Rout MP. Proteins connecting the nuclear pore complex with the nuclear interior. J Cell Biol. 1999 Mar 08; 144(5):839-55. PMID: 10085285.
      Citations: 110     Fields:    Translation:AnimalsCells
    30. 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. PMID: 9736720.
      Citations: 26     Fields:    Translation:Cells
    31. Strambio-De-Castillia C. Identification and characterization of Mlp1p and Mlp2p: Molecular components of filaments localized at the interface between the nuclear pore complex and the nuclear interior. Ph.D. Thesis dissertation. The Rockefeller University, New York, NY, USA. 1998.
    32. 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.
    33. 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. PMID: 7559775.
      Citations: 40     Fields:    Translation:AnimalsCells
    34. 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. PMID: 7642562.
      Citations: 65     Fields:    Translation:AnimalsCells
    35. 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. PMID: 1279197.
      Citations: 68     Fields:    Translation:HumansAnimalsCells
    36. Strambio-De-Castillia C. Presence of Transcriptional Elements in Putative Human Replication Origins. Doctoral thesis dissertation. Universita' degli Studi di Pavia, Pavia, Italy. 1988.
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