Research Topics
Species | Michael CahalanSummaryAffiliation: University of California Country: USA Publications
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Publications
Antigen-engaged B cells undergo chemotaxis toward the T zone and form motile conjugates with helper T cellsTakaharu Okada
Howard Hughes Medical Institute, Department of Microbiology and Immunology, University of California, San Francisco, California, USA
PLoS Biol 3:e150. 2005..These findings provide evidence of lymphocyte chemotaxis in vivo, and they begin to define the spatiotemporal cellular dynamics associated with T cell-dependent antibody responses...
The immunological synapse: a dynamic platform for local signalingMatthew F Krummel
Department of Pathology, University of California San Francisco, 513 Parnassus Avenue HSW 0511, San Francisco, CA 94143, USA
J Clin Immunol 30:364-72. 2010..Such spatiotemporal signaling in the synapse greatly accelerates kinetics and provides essential checkpoints to validate effective cell-cell communication...
Ion channels in the immune system as targets for immunosuppressionM D Cahalan
Department of Physiology and Biophysics, University of California, Irvine 92697 4560, USA
Curr Opin Biotechnol 8:749-56. 1997..Ion channels may provide excellent pharmaceutical targets for modulating immune system function...
The sense of place in the immune systemMichael D Cahalan
Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA
Nat Immunol 7:329-32. 2006....
Molecular basis of the CRAC channelMichael D Cahalan
Department of Physiology and Biophysics and Center for Immunology, University of California, Irvine, CA 92697, United States
Cell Calcium 42:133-44. 2007....
Choreography of cell motility and interaction dynamics imaged by two-photon microscopy in lymphoid organsMichael D Cahalan
Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA
Annu Rev Immunol 26:585-626. 2008....
Close encounters of the first and second kind: T-DC and T-B interactions in the lymph nodeMichael D Cahalan
Department of Physiology and Biophysics and Center for Immunology, University of California, Irvine, CA 92697 4561, USA
Semin Immunol 17:442-51. 2005..In this topical review, we compare the activation choreography of CD4+ T cells interacting first with dendritic cells, and then with B cells, during initiation of the humoral immune response...
Real-time imaging of lymphocytes in vivoMichael D Cahalan
Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA
Curr Opin Immunol 15:372-7. 2003..The view is emerging that lymphocytes migrate randomly within lymphoid organs, and that lymphocyte contact with antigen-presenting cells may be a stochastic process rather than one guided by chemokine gradients...
STIMulating store-operated Ca(2+) entryMichael D Cahalan
Department of Physiology and Biophysics and Institute for Immunology, University of California, Irvine, CA 92697 4561, USA
Nat Cell Biol 11:669-77. 2009....
Molecular properties and physiological roles of ion channels in the immune systemM D Cahalan
Department of Physiology and Biophysics, University of California, Irvine 92697, USA
J Clin Immunol 21:235-52. 2001..This review surveys recent progress at the biophysical, molecular, and functional roles of the ion channels found in T lymphocytes...
The functional network of ion channels in T lymphocytesMichael D Cahalan
Department of Physiology and Biophysics, and the Institute for Immunology, University of California, Irvine, Irvine, CA 92697 4561, USA
Immunol Rev 231:59-87. 2009....
STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membraneShenyuan L Zhang
Department of Physiology and Biophysics and Center for Immunology, University of California, Irvine, California 92697, USA
Nature 437:902-5. 2005..We propose that STIM1 functions as the missing link between Ca2+ store depletion and SOC influx, serving as a Ca2+ sensor that translocates upon store depletion to the plasma membrane to activate CRAC channels...
Orai1 and STIM1 move to the immunological synapse and are up-regulated during T cell activationMaria I Lioudyno
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
Proc Natl Acad Sci U S A 105:2011-6. 2008..These results imply a positive feedback loop in which an initial TCR signal favors up-regulation of STIM1 and Orai proteins that would augment Ca2+ signaling during subsequent antigen encounter...
Imaging the choreography of lymphocyte trafficking and the immune responseMichael D Cahalan
Department of Physiology and Biophysics and Neurobiology and Behavior, University of California, Irvine, 92697, USA
Curr Opin Immunol 18:476-82. 2006..Recently, advances have been made in these areas of research, as exemplified by studies investigating T cell-dendritic cell interactions, T cell-B cell interactions, and the regulation of lymphocyte egress from the lymph node...
Two-photon imaging of lymphocyte motility and antigen response in intact lymph nodeMark J Miller
Department of Physiology and Biophysics, University of California, Irvine, CA 92697-4561, USA
Science 296:1869-73. 2002..Antigenic challenge changed T cell trajectories from random walks to "swarms" and stable clusters. Real-time two-photon imaging reveals lymphocyte behaviors that are fundamental to the initiation of the immune response...
Imaging of effector memory T cells during a delayed-type hypersensitivity reaction and suppression by Kv1.3 channel blockMelanie P Matheu
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697 4561, USA
Immunity 29:602-14. 2008..3 channels in Tem cells during an inflammatory immune response in peripheral tissues. Targeting Kv1.3 allows for effector memory responses to be suppressed while central memory responses remain intact...
Ca2+ signals in CD4+ T cells during early contacts with antigen-bearing dendritic cells in lymph nodeSindy H Wei
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
J Immunol 179:1586-94. 2007..We propose that sustained increases in basal [Ca(2+)](i) and spiking frequency constitute a Ca(2+) signaling modality that, integrated over hours, distinguishes immunogenic from basal state in the native lymphoid environment...
K+ channels as targets for specific immunomodulationK George Chandy
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
Trends Pharmacol Sci 25:280-9. 2004..3 and IKCa1 channels, and provide a rationale for the potential therapeutic use of these inhibitors in immunological disorders...
Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodesMark J Miller
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
J Exp Med 200:847-56. 2004..Furthermore, the serial nature of these interactions implies that T cells activate by way of multiple antigen recognition events...
Two-photon imaging in intact lymphoid tissueSindy H Wei
Department of Physiology and Biophysics, University of California, Irvine 92697-4561, USA
Adv Exp Med Biol 512:203-8. 2002
Two-photon tissue imaging: seeing the immune system in a fresh lightMichael D Cahalan
Department of Physiology, University of California, Irvine, California 92697 4561, USA
Nat Rev Immunol 2:872-80. 2002..Two-photon microscopy, in combination with newly developed indicator molecules, promises to extend single-cell approaches to the in vivo setting and to reveal in detail the cellular collaborations that underlie the immune response...
Class IA phosphoinositide 3-kinase modulates basal lymphocyte motility in the lymph nodeMelanie P Matheu
Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA
J Immunol 179:2261-9. 2007..Moreover, we demonstrate distinct roles for catalytic domain function and class IA PI3K regulatory domain activity in lymphocyte motility, homing, and homeostatic localization of mature resting B cells...
Quantum dots for tracking dendritic cells and priming an immune response in vitro and in vivoDebasish Sen
Department of Physiology and Biophysics, University of California Irvine, Irvine, California, United States of America
PLoS ONE 3:e3290. 2008..These results establish QDs as a versatile platform for immunoimaging of dendritic cells and as an efficient nanoparticle-based antigen delivery system for priming an immune response...
Store-dependent and -independent modes regulating Ca2+ release-activated Ca2+ channel activity of human Orai1 and Orai3Shenyuan L Zhang
Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA
J Biol Chem 283:17662-71. 2008..The Orai3 current induced by 2-APB may reflect a store-independent mode of CRAC channel activation that opens a relatively nonselective cation pore...
Molecular identification of the CRAC channel by altered ion selectivity in a mutant of OraiAndriy V Yeromin
Department of Physiology and Biophysics and Center for Immunology, University of California, Irvine, California 92697, USA
Nature 443:226-9. 2006..These results indicate that Orai itself forms the Ca2+-selectivity filter of the CRAC channel...
Autonomous T cell trafficking examined in vivo with intravital two-photon microscopyMark J Miller
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
Proc Natl Acad Sci U S A 100:2604-9. 2003....
Regulation of membrane trafficking and subcellular organization of endocytic compartments revealed with FM1-43 in resting and activated human T cellsAlla F Fomina
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
Exp Cell Res 291:150-66. 2003..The present study demonstrates the utility of FM1-43 as a marker of membrane trafficking in T cells and reveals possible mechanisms of its modulation during T cell activation...
Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activityShenyuan L Zhang
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
Proc Natl Acad Sci U S A 103:9357-62. 2006....
A novel fluorescent toxin to detect and investigate Kv1.3 channel up-regulation in chronically activated T lymphocytesChristine Beeton
Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA
J Biol Chem 278:9928-37. 2003..3 up-regulation. ShK-F6CA might be useful for rapid and quantitative detection of Kv1.3(high) expressing cells in normal and diseased tissues, and to visualize the distribution of functional channels in intact cells...
Distinct properties of CRAC and MIC channels in RBL cellsJ Ashot Kozak
Department of Physiology and Biophysics, University of California at Irvine, Irvine, CA 92697, USA
J Gen Physiol 120:221-35. 2002..The biophysical characteristics of MIC current match well with cloned and expressed TRPM7 channels. Previous results are reevaluated in terms of separate CRAC and MIC channels...
The CRAC channel consists of a tetramer formed by Stim-induced dimerization of Orai dimersAubin Penna
Department of Physiology and Biophysics, University of California Irvine, California 92697 4561, USA
Nature 456:116-20. 2008..This represents a new mechanism in which assembly and activation of the functional ion channel are mediated by the same triggering molecule...
Polyvalent cations as permeant probes of MIC and TRPM7 poresHubert H Kerschbaum
Department of Physiology and Biophysics, University of California, Irvine, California 92697-4561 USA
Biophys J 84:2293-305. 2003..An Eyring rate model is developed to account for I/V characteristics and block of MIC channels by polyvalent cations from the outside...
A stochastic view of lymphocyte motility and trafficking within the lymph nodeSindy H Wei
Departments of Physiology and Biophysics, University of California, Irvine, CA 92697-4561, USA
Immunol Rev 195:136-59. 2003....
Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinusesSindy H Wei
Department of Physiology and Biophysics and Center for Immunology, University of California, Irvine, California 92697 4561, USA
Nat Immunol 6:1228-35. 2005..Our results provide visualization of transendothelial migration of T cells into lymphatic sinuses and suggest that S1P(1) agonists act mainly on endothelial cell S1P(1) receptors to inhibit lymphocyte migration...
SK3-1C, a dominant-negative suppressor of SKCa and IKCa channelsAaron Kolski-Andreaco
Department of Physiology and Biophysics, University of California Irvine, Irvine, California 92697, USA
J Biol Chem 279:6893-904. 2004....
T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph nodeMark J Miller
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
Proc Natl Acad Sci U S A 101:998-1003. 2004..We conclude that dynamic DC gesticulation and random T cell motility together enhance the stochastic scanning of the T cell repertoire, thereby enabling rapid initiation of the immune response...
Natural killer cells actively patrol peripheral lymph nodes forming stable conjugates to eliminate MHC-mismatched targetsKym R Garrod
Department of Physiology, University of California, Irvine, CA 92697 4561, USA
Proc Natl Acad Sci U S A 104:12081-6. 2007..Taken together our data demonstrate that NK cells are a functionally important component of the LN microenvironment, and that cell motility and effector function are strongly modulated via CD49b manipulation...
A store-operated calcium channel in Drosophila S2 cellsAndriy V Yeromin
Department of Physiology and Biophysics, University of California, Irvine, CA 92697-4561, USA
J Gen Physiol 123:167-82. 2004..We conclude that S2 cells express store-operated Ca2+ channels with many of the same biophysical characteristics as CRAC channels in mammalian cells...
Modulation of mouse Paneth cell alpha-defensin secretion by mIKCa1, a Ca2+-activated, intermediate conductance potassium channelTokiyoshi Ayabe
Department of Pathology, College of Medicine, University of California, Irvine, California 92697 4800, USA
J Biol Chem 277:3793-800. 2002..These results demonstrate that mIKCa1 is modulator of Paneth cell alpha-defensin secretion and disclose an involvement in mucosal defense of the intestinal epithelium against ingested bacterial pathogens...
NK cell patrolling and elimination of donor-derived dendritic cells favor indirect alloreactivityKym R Garrod
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
J Immunol 184:2329-36. 2010..We thus propose that rapid elimination of allogeneic DCs limits direct Ag presentation and thereby favors the indirect pathway of alloreactivity...
MIC channels are inhibited by internal divalent cations but not ATPJ Ashot Kozak
Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA
Biophys J 84:922-7. 2003..We conclude that MIC current inhibition occurs simply by divalent cations...
Selective and site-specific mobilization of dermal dendritic cells and Langerhans cells by Th1- and Th2-polarizing adjuvantsDebasish Sen
Department of Physiology and Biophysics and Institute for Immunology, University of California, Irvine, CA 92697 4561, USA
Proc Natl Acad Sci U S A 107:8334-9. 2010....
STIM1, an essential and conserved component of store-operated Ca2+ channel functionJack Roos
Torrey Pines Therapeutics, Inc, La Jolla, CA 92037, USA
J Cell Biol 169:435-45. 2005..We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels...
Channel function is dissociated from the intrinsic kinase activity and autophosphorylation of TRPM7/ChaK1Masayuki Matsushita
First Department of Physiology, Okayama University Medical School, 2 5 1 Shikata cho, Okayama 700 8558, Japan
J Biol Chem 280:20793-803. 2005..We conclude that neither current activity nor regulation by internal Mg(2+) is affected by kinase activity or autophosphorylation but that the kinase domain may play a structural role in channel assembly or subcellular localization...
The ins and outs of polycystin-2 as a calcium release channelMichael D Cahalan
Nat Cell Biol 4:E56-7. 2002
Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivoM Germana Sanna
Department of Immunology and The Scripps Research Institute Molecular Screening Center, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Chem Biol 2:434-41. 2006..Thus, chemical modulation reveals differences in S1P-S1P1 'set points' among tissues and highlights both mechanistic advantages (lymphocyte sequestration) and risks (pulmonary edema) of therapeutic intervention...
STOP! In the name of positive selectionMichael D Cahalan
Nat Immunol 6:126-8. 2005
Research Grants
- Functional immuno-imaging of lymphocyte motility and cell interactions in lymph nMichael D Cahalan; Fiscal Year: 2010..The second goal is to investigate immunosuppression mediated by blockade of specific ion channels in T lymphocytes - a potassium channel Kv1.3 and a calcium channel Orai1 - for treatment of autoimmune disorders. ..
- CALCIUM IONS AND LYMPHOCYTE ACTIVATIONMichael Cahalan; Fiscal Year: 2000..They are investigating interactions between cells during antigen presentation, as well as intracellular signaling mechanisms that link membrane receptors with gene expression. ..
- MOLECULAR MECHANISMS OF ION CHANNELS IN CELL MEMBRANESMichael Cahalan; Fiscal Year: 2000..Through the proposed experiments we hope to define mechanisms that regulate ion channels and corresponding cell functions that underlie the immune response. ..
- Functional Imaging of Lymphocyte Motility and Cell Interactions in Lymph NodeMichael Cahalan; Fiscal Year: 2009..abstract_text> ..
- Functional Imaging of Lymphocyte Motility and Cell Interactions in Lymph NodeMichael Cahalan; Fiscal Year: 2007....
- Molecular Mechanisms of Ion Channels in T LymphocytesMichael Cahalan; Fiscal Year: 2007....
- Molecular Mechanisms of Ion Channel in Cell MembranesMichael Cahalan; Fiscal Year: 2005..Through the proposed experiments we hope to define mechanisms that regulate ion channels and corresponding cell functions that underlie the immune response. ..
- The Role of Calcium Ions in Lymphocyte ActivationMichael Cahalan; Fiscal Year: 2005..A further goal of this project is to compare the functional responses of quiescent, activated, and chronically activated auto reactive T cells in light of their differing ion channel phenotypes. ..
- MOLECULAR MECHANISMS IN EXCITABLE MEMBRANESMichael Cahalan; Fiscal Year: 1980..In addition to furthering our knowledge of neurotoxins, local anesthetics, and other pharmacologically important compounds, this research aims at a better understanding of normal molecular mechanisms in excitable membranes...
- CALCIUM IONS AND LYMPHOCYTE ACTIVATIONMichael Cahalan; Fiscal Year: 1993..The distribution of ATP receptors in cells of the immune system will be determined. Collectively, these experiments make use of a single-cell approach to clarify signal transduction mechanisms vital to immune system function...
- MOLECULAR MECHANISMS OF ION CHANNELS IN CELL MEMBRANESMichael Cahalan; Fiscal Year: 1993....
- ROLE OF ION CHANNELS IN LYMPHOCYTE ACTIVATIONMichael Cahalan; Fiscal Year: 1992....
