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

Activating sphingosine-1-phospahte signaling in endothelial cells increases myosin light chain phosphorylation to decrease endothelial permeability thereby inhibiting cancer metastasis.
Authors: Authors: Chen YC, Dinavahi SS, Feng Q, Gowda R, Ramisetti S, Xia X, LaPenna KB, Chirasani VR, Cho SH, Hafenstein SL, Battu MB, Berg A, Sharma AK, Kirchhausen T, Dokholyan NV, Amin S, He P, Robertson GP.
Cancer Lett
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Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion.
Authors: Authors: Zang R, Case JB, Yutuc E, Ma X, Shen S, Gomez Castro MF, Liu Z, Zeng Q, Zhao H, Son J, Rothlauf PW, Kreutzberger AJB, Hou G, Zhang H, Bose S, Wang X, Vahey MD, Mani K, Griffiths WJ, Kirchhausen T, Fremont DH, Guo H, Diwan A, Wang Y, Diamond MS, Whelan SPJ, Ding S.
Proc Natl Acad Sci U S A
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Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface.
Authors: Authors: Shipley FB, Dani N, Xu H, Deister C, Cui J, Head JP, Sadegh C, Fame RM, Shannon ML, Flores VI, Kishkovich T, Jang E, Klein EM, Goldey GJ, He K, Zhang Y, Holtzman MJ, Kirchhausen T, Wyart C, Moore CI, Andermann ML, Lehtinen MK.
Neuron
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HDAC6 mediates an aggresome-like mechanism for NLRP3 and pyrin inflammasome activation.
Authors: Authors: Magupalli VG, Negro R, Tian Y, Hauenstein AV, Di Caprio G, Skillern W, Deng Q, Orning P, Alam HB, Maliga Z, Sharif H, Hu JJ, Evavold CL, Kagan JC, Schmidt FI, Fitzgerald KA, Kirchhausen T, Li Y, Wu H.
Science
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Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2.
Authors: Authors: Kang YL, Chou YY, Rothlauf PW, Liu Z, Soh TK, Cureton D, Case JB, Chen RE, Diamond MS, Whelan SPJ, Kirchhausen T.
Proc Natl Acad Sci U S A
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Oligomerization of the Vesicular Stomatitis Virus Phosphoprotein Is Dispensable for mRNA Synthesis but Facilitates RNA Replication.
Authors: Authors: Bloyet LM, Morin B, Brusic V, Gardner E, Ross RA, Vadakkan T, Kirchhausen T, Whelan SPJ.
J Virol
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Inhibition of PIKfyve kinase prevents infection by EBOV and SARS-CoV-2.
Authors: Authors: Kang YL, Chou YY, Rothlauf PW, Liu Z, Soh TK, Cureton D, Case JB, Chen RE, Diamond MS, Whelan SPJ, Kirchhausen T.
bioRxiv
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Dynamics of Auxilin 1 and GAK in clathrin-mediated traffic.
Authors: Authors: He K, Song E, Upadhyayula S, Dang S, Gaudin R, Skillern W, Bu K, Capraro BR, Rapoport I, Kusters I, Ma M, Kirchhausen T.
J Cell Biol
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Correlative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cells.
Authors: Authors: Hoffman DP, Shtengel G, Xu CS, Campbell KR, Freeman M, Wang L, Milkie DE, Pasolli HA, Iyer N, Bogovic JA, Stabley DR, Shirinifard A, Pang S, Peale D, Schaefer K, Pomp W, Chang CL, Lippincott-Schwartz J, Kirchhausen T, Solecki DJ, Betzig E, Hess HF.
Science
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Design and Validation of a Human Brain Endothelial Microvessel-on-a-Chip Open Microfluidic Model Enabling Advanced Optical Imaging.
Authors: Authors: Salman MM, Marsh G, Kusters I, Delincé M, Di Caprio G, Upadhyayula S, de Nola G, Hunt R, Ohashi KG, Gray T, Shimizu F, Sano Y, Kanda T, Obermeier B, Kirchhausen T.
Front Bioeng Biotechnol
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