Tomas Kirchhausen, Ph.D.

Tomas Kirchhausen, Ph.D.

Senior Investigator, Program in Cellular and Molecular Medicine (Boston Children's Hospital)
Springer Family Professor of Pediatrics (HMS)
Professor of Cell Biology (HMS)

The Kirchhausen Lab focuses on understanding processes that mediate and regulate cellular membrane remodeling, the biogenesis of organelles, and the ways by which viruses, biologicals and oligonucleotides are delivered to the cell interior. 

By direct observation of molecular events obtained using Lattice Light Sheet Microscopy and Lattice Light Sheet Microscopy optimized with Adaptive Optics (AO-LLSM), frontier optical-imaging modalities with high temporal resolution and spatial precision, we aim to bridge the gap between molecules and cells, either as independent entities in culture, as components of organoids, or as constituents of living tissues. The richness and magnitude of the big-data obtained over periods ranging from seconds to hours create new challenges for obtaining quantitative representations of the observed dynamics and for deriving accurate and comprehensive models for the underlying developmental mechanisms. With these type of dynamic studies we expect to integrate molecular snapshots obtained at molecular and atomic resolution using cryoEM with live-cell processes, in an effort to generate ‘molecular movies' allowing us to obtain frameworks for analyzing some of the molecular contacts and switches that participate in the regulation, availability, and intracellular traffic of the many molecules involved in signal transduction, immune responsiveness, lipid homeostasis, cell-cell recognition and organelle biogenesis. Such biological phenomena have importance for our understanding of many diseases including cancer, viral infection and pathogen invasion, Alzheimer's, as well as other neurological diseases.

Harvard Medical School

Dept. of Cell Biology, WAB-133

200 Longwood Avenue

Boston, MA 02115

Lab telephone: 617-713-8888

Lab fax: 617-713-8898

The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles.
Authors: Authors: Coulter ME, Dorobantu CM, Lodewijk GA, Delalande F, Cianferani S, Ganesh VS, Smith RS, Lim ET, Xu CS, Pang S, Wong ET, Lidov HGW, Calicchio ML, Yang E, Gonzalez DM, Schlaeger TM, Mochida GH, Hess H, Lee WA, Lehtinen MK, Kirchhausen T, Haussler D, Jacobs FMJ, Gaudin R, Walsh CA.
Cell Rep
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Lamellar projections in the endolymphatic sac act as a relief valve to regulate inner ear pressure.
Authors: Authors: Swinburne IA, Mosaliganti KR, Upadhyayula S, Liu TL, Hildebrand DGC, Tsai TY, Chen A, Al-Obeidi E, Fass AK, Malhotra S, Engert F, Lichtman JW, Kirchhausen T, Betzig E, Megason SG.
Elife
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Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms.
Authors: Authors: Liu TL, Upadhyayula S, Milkie DE, Singh V, Wang K, Swinburne IA, Mosaliganti KR, Collins ZM, Hiscock TW, Shea J, Kohrman AQ, Medwig TN, Dambournet D, Forster R, Cunniff B, Ruan Y, Yashiro H, Scholpp S, Meyerowitz EM, Hockemeyer D, Drubin DG, Martin BL, Matus DQ, Koyama M, Megason SG, Kirchhausen T, Betzig E.
Science
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Reconstitution of Clathrin Coat Disassembly for Fluorescence Microscopy and Single-Molecule Analysis.
Authors: Authors: Böcking T, Upadhyayula S, Rapoport I, Capraro BR, Kirchhausen T.
Methods Mol Biol
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Dynamics of phosphoinositide conversion in clathrin-mediated endocytic traffic.
Authors: Authors: He K, Marsland R, Upadhyayula S, Song E, Dang S, Capraro BR, Wang W, Skillern W, Gaudin R, Ma M, Kirchhausen T.
Nature
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NRP2 and CD63 Are Host Factors for Lujo Virus Cell Entry.
Authors: Authors: Raaben M, Jae LT, Herbert AS, Kuehne AI, Stubbs SH, Chou YY, Blomen VA, Kirchhausen T, Dye JM, Brummelkamp TR, Whelan SP.
Cell Host Microbe
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Ectopic expression of RAD52 and dn53BP1 improves homology-directed repair during CRISPR-Cas9 genome editing.
Authors: Authors: Paulsen BS, Mandal PK, Frock RL, Boyraz B, Yadav R, Upadhyayula S, Gutierrez-Martinez P, Ebina W, Fasth A, Kirchhausen T, Talkowski ME, Agarwal S, Alt FW, Rossi DJ.
Nat Biomed Eng
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Recruitment dynamics of ESCRT-III and Vps4 to endosomes and implications for reverse membrane budding.
Authors: Authors: Adell MAY, Migliano SM, Upadhyayula S, Bykov YS, Sprenger S, Pakdel M, Vogel GF, Jih G, Skillern W, Behrouzi R, Babst M, Schmidt O, Hess MW, Briggs JA, Kirchhausen T, Teis D.
Elife
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Miro1-mediated mitochondrial positioning shapes intracellular energy gradients required for cell migration.
Authors: Authors: Schuler MH, Lewandowska A, Caprio GD, Skillern W, Upadhyayula S, Kirchhausen T, Shaw JM, Cunniff B.
Mol Biol Cell
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Inhibition of JCPyV infection mediated by targeted viral genome editing using CRISPR/Cas9.
Authors: Authors: Chou YY, Krupp A, Kaynor C, Gaudin R, Ma M, Cahir-McFarland E, Kirchhausen T.
Sci Rep
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