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    Kevin E Fogarty MS

    TitleResearch Assistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    373 Plantation Street
    Worcester MA 01605
    Phone508-856-3785
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentMicrobiology and Physiological Systems

        Overview 
        Narrative

        Academic Background

        1975, B.S., Worcester Polytechnic Institute
        1979, M.S., Worcester Polytechnic Institute

        Imaging Molecular and Cellular Dynamics with Light Microscopy in Living Cells

        Research in this lab is concerned with the both the development and the application of light microscopy and imaging in cell biology and biophysics. Some driving problems include imaging the molecular components driving endocytosis and exocytosis/secretion in various cell types, and the imaging of intracellular calcium signaling in excitable cells such as smooth muscle cells, chromaffin cells, and neurons. We have developed the TESM microscope that combines Total internal reflection fluorescence (TIRF) with Epi-fluorescence Structured illumination to provide new views of trafficking in the near-plasma membrane domain of cells. We have a unique, custom built, ultra-high speed microscope system for imaging the dynamics of intracellular calcium channel events, called "calcium sparks", that are being found to regulate an expanding array of cellular processes. We have a two-photon fluorescence microscope for looking deep inside tissue, completing the range from molecule to organism. Areas of on-going technology research include high-speed, high-resolution imaging of live cells and tissues, novel image processing approaches, high performance computing and computer graphics, with an emphasis on developing open source tools for the research community.

        Figure

        Research Figure



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Gabriel LR, Wu S, Kearney P, Bellvé KD, Standley C, Fogarty KE, Melikian HE. Dopamine transporter endocytic trafficking in striatal dopaminergic neurons: differential dependence on dynamin and the actin cytoskeleton. J Neurosci. 2013 Nov 6; 33(45):17836-46.
          View in: PubMed
        2. Zhang CH, Lifshitz LM, Uy KF, Ikebe M, Fogarty KE, ZhuGe R. The cellular and molecular basis of bitter tastant-induced bronchodilation. PLoS Biol. 2013; 11(3):e1001501.
          View in: PubMed
        3. Zhang CH, Chen C, Lifshitz LM, Fogarty KE, Zhu MS, ZhuGe R. Activation of BK channels may not be required for bitter tastant-induced bronchodilation. Nat Med. 2012 May; 18(5):648-50; author reply 650-1.
          View in: PubMed
        4. Guo D, Standley C, Bellve K, Fogarty K, Bao ZZ. Protein kinase Ca and integrin-linked kinase mediate the negative axon guidance effects of Sonic hedgehog. Mol Cell Neurosci. 2012 May; 50(1):82-92.
          View in: PubMed
        5. Navaroli DM, Bellvé KD, Standley C, Lifshitz LM, Cardia J, Lambright D, Leonard D, Fogarty KE, Corvera S. Rabenosyn-5 defines the fate of the transferrin receptor following clathrin-mediated endocytosis. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):E471-80.
          View in: PubMed
        6. Goel HL, Pursell B, Standley C, Fogarty K, Mercurio AM. Neuropilin-2 regulates a6ß1 integrin in the formation of focal adhesions and signaling. J Cell Sci. 2012 Jan 15; 125(Pt 2):497-506.
          View in: PubMed
        7. De Crescenzo V, Fogarty KE, Lefkowitz JJ, Bellve KD, Zvaritch E, MacLennan DH, Walsh JV. Type 1 ryanodine receptor knock-in mutation causing central core disease of skeletal muscle also displays a neuronal phenotype. Proc Natl Acad Sci U S A. 2012 Jan 10; 109(2):610-5.
          View in: PubMed
        8. Lifshitz LM, Carmichael JD, Lai FA, Sorrentino V, Bellvé K, Fogarty KE, ZhuGe R. Spatial organization of RYRs and BK channels underlying the activation of STOCs by Ca(2+) sparks in airway myocytes. J Gen Physiol. 2011 Aug; 138(2):195-209.
          View in: PubMed
        9. Schmolze DB, Standley C, Fogarty KE, Fischer AH. Advances in microscopy techniques. Arch Pathol Lab Med. 2011 Feb; 135(2):255-63.
          View in: PubMed
        10. Jurczyk A, Pino SC, O'Sullivan-Murphy B, Addorio M, Lidstone EA, Diiorio P, Lipson KL, Standley C, Fogarty K, Lifshitz L, Urano F, Mordes JP, Greiner DL, Rossini AA, Bortell R. A novel role for the centrosomal protein, pericentrin, in regulation of insulin secretory vesicle docking in mouse pancreatic beta-cells. PLoS One. 2010; 5(7):e11812.
          View in: PubMed
        11. Zhou QL, Jiang ZY, Mabardy AS, Del Campo CM, Lambright DG, Holik J, Fogarty KE, Straubhaar J, Nicoloro S, Chawla A, Czech MP. A novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytes. J Biol Chem. 2010 Sep 3; 285(36):27581-9.
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        12. Nicoli S, Standley C, Walker P, Hurlstone A, Fogarty KE, Lawson ND. MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature. 2010 Apr 22; 464(7292):1196-200.
          View in: PubMed
        13. Zhuge R, Bao R, Fogarty KE, Lifshitz LM. Ca2+ sparks act as potent regulators of excitation-contraction coupling in airway smooth muscle. J Biol Chem. 2010 Jan 15; 285(3):2203-10.
          View in: PubMed
        14. McNally JM, De Crescenzo V, Fogarty KE, Walsh JV, Lemos JR. Individual calcium syntillas do not trigger spontaneous exocytosis from nerve terminals of the neurohypophysis. J Neurosci. 2009 Nov 11; 29(45):14120-6.
          View in: PubMed
        15. Lefkowitz JJ, Fogarty KE, Lifshitz LM, Bellve KD, Tuft RA, ZhuGe R, Walsh JV, De Crescenzo V. Suppression of Ca2+ syntillas increases spontaneous exocytosis in mouse adrenal chromaffin cells. J Gen Physiol. 2009 Oct; 134(4):267-80.
          View in: PubMed
        16. Siekmann AF, Standley C, Fogarty KE, Wolfe SA, Lawson ND. Chemokine signaling guides regional patterning of the first embryonic artery. Genes Dev. 2009 Oct 1; 23(19):2272-7.
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        17. Li X, Standley C, Sapp E, Valencia A, Qin ZH, Kegel KB, Yoder J, Comer-Tierney LA, Esteves M, Chase K, Alexander J, Masso N, Sobin L, Bellve K, Tuft R, Lifshitz L, Fogarty K, Aronin N, DiFiglia M. Mutant huntingtin impairs vesicle formation from recycling endosomes by interfering with Rab11 activity. Mol Cell Biol. 2009 Nov; 29(22):6106-16.
          View in: PubMed
        18. Kolpak AL, Jiang J, Guo D, Standley C, Bellve K, Fogarty K, Bao ZZ. Negative guidance factor-induced macropinocytosis in the growth cone plays a critical role in repulsive axon turning. J Neurosci. 2009 Aug 26; 29(34):10488-98.
          View in: PubMed
        19. Leonard D, Hayakawa A, Lawe D, Lambright D, Bellve KD, Standley C, Lifshitz LM, Fogarty KE, Corvera S. Sorting of EGF and transferrin at the plasma membrane and by cargo-specific signaling to EEA1-enriched endosomes. J Cell Sci. 2008 Oct 15; 121(Pt 20):3445-58.
          View in: PubMed
        20. Bao R, Lifshitz LM, Tuft RA, Bellvé K, Fogarty KE, ZhuGe R. A close association of RyRs with highly dense clusters of Ca2+-activated Cl- channels underlies the activation of STICs by Ca2+ sparks in mouse airway smooth muscle. J Gen Physiol. 2008 Jul; 132(1):145-60.
          View in: PubMed
        21. Zhang YA, Tuft RA, Lifshitz LM, Fogarty KE, Singer JJ, Zou H. Caffeine-activated large-conductance plasma membrane cation channels in cardiac myocytes: characteristics and significance. Am J Physiol Heart Circ Physiol. 2007 Oct; 293(4):H2448-61.
          View in: PubMed
        22. Huang S, Lifshitz LM, Jones C, Bellve KD, Standley C, Fonseca S, Corvera S, Fogarty KE, Czech MP. Insulin stimulates membrane fusion and GLUT4 accumulation in clathrin coats on adipocyte plasma membranes. Mol Cell Biol. 2007 May; 27(9):3456-69.
          View in: PubMed
        23. Hayakawa A, Leonard D, Murphy S, Hayes S, Soto M, Fogarty K, Standley C, Bellve K, Lambright D, Mello C, Corvera S. The WD40 and FYVE domain containing protein 2 defines a class of early endosomes necessary for endocytosis. Proc Natl Acad Sci U S A. 2006 Aug 8; 103(32):11928-33.
          View in: PubMed
        24. De Crescenzo V, Fogarty KE, Zhuge R, Tuft RA, Lifshitz LM, Carmichael J, Bellvé KD, Baker SP, Zissimopoulos S, Lai FA, Lemos JR, Walsh JV. Dihydropyridine receptors and type 1 ryanodine receptors constitute the molecular machinery for voltage-induced Ca2+ release in nerve terminals. J Neurosci. 2006 Jul 19; 26(29):7565-74.
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        25. Chau MD, Tuft R, Fogarty K, Bao ZZ. Notch signaling plays a key role in cardiac cell differentiation. Mech Dev. 2006 Aug; 123(8):626-40.
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        26. Follit JA, Tuft RA, Fogarty KE, Pazour GJ. The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly. Mol Biol Cell. 2006 Sep; 17(9):3781-92.
          View in: PubMed
        27. Bellve KD, Leonard D, Standley C, Lifshitz LM, Tuft RA, Hayakawa A, Corvera S, Fogarty KE. Plasma membrane domains specialized for clathrin-mediated endocytosis in primary cells. J Biol Chem. 2006 Jun 9; 281(23):16139-46.
          View in: PubMed
        28. ZhuGe R, DeCrescenzo V, Sorrentino V, Lai FA, Tuft RA, Lifshitz LM, Lemos JR, Smith C, Fogarty KE, Walsh JV. Syntillas release Ca2+ at a site different from the microdomain where exocytosis occurs in mouse chromaffin cells. Biophys J. 2006 Mar 15; 90(6):2027-37.
          View in: PubMed
        29. Politz JC, Tuft RA, Prasanth KV, Baudendistel N, Fogarty KE, Lifshitz LM, Langowski J, Spector DL, Pederson T. Rapid, diffusional shuttling of poly(A) RNA between nuclear speckles and the nucleoplasm. Mol Biol Cell. 2006 Mar; 17(3):1239-49.
          View in: PubMed
        30. Turvey MR, Fogarty KE, Thorn P. Inositol (1,4,5)-trisphosphate receptor links to filamentous actin are important for generating local Ca2+ signals in pancreatic acinar cells. J Cell Sci. 2005 Mar 1; 118(Pt 5):971-80.
          View in: PubMed
        31. Huang S, Lifshitz L, Patki-Kamath V, Tuft R, Fogarty K, Czech MP. Phosphatidylinositol-4,5-bisphosphate-rich plasma membrane patches organize active zones of endocytosis and ruffling in cultured adipocytes. Mol Cell Biol. 2004 Oct; 24(20):9102-23.
          View in: PubMed
        32. Zou H, Lifshitz LM, Tuft RA, Fogarty KE, Singer JJ. Using total fluorescence increase (signal mass) to determine the Ca2+ current underlying localized Ca2+ events. J Gen Physiol. 2004 Sep; 124(3):259-72.
          View in: PubMed
        33. Zhuge R, Fogarty KE, Baker SP, McCarron JG, Tuft RA, Lifshitz LM, Walsh JV. Ca(2+) spark sites in smooth muscle cells are numerous and differ in number of ryanodine receptors, large-conductance K(+) channels, and coupling ratio between them. Am J Physiol Cell Physiol. 2004 Dec; 287(6):C1577-88.
          View in: PubMed
        34. Zou H, Lifshitz LM, Tuft RA, Fogarty KE, Singer JJ. Imaging calcium entering the cytosol through a single opening of plasma membrane ion channels: SCCaFTs--fundamental calcium events. Cell Calcium. 2004 Jun; 35(6):523-33.
          View in: PubMed
        35. Bose A, Robida S, Furcinitti PS, Chawla A, Fogarty K, Corvera S, Czech MP. Unconventional myosin Myo1c promotes membrane fusion in a regulated exocytic pathway. Mol Cell Biol. 2004 Jun; 24(12):5447-58.
          View in: PubMed
        36. Thorn P, Fogarty KE, Parker I. Zymogen granule exocytosis is characterized by long fusion pore openings and preservation of vesicle lipid identity. Proc Natl Acad Sci U S A. 2004 Apr 27; 101(17):6774-9.
          View in: PubMed
        37. De Crescenzo V, ZhuGe R, Velázquez-Marrero C, Lifshitz LM, Custer E, Carmichael J, Lai FA, Tuft RA, Fogarty KE, Lemos JR, Walsh JV. Ca2+ syntillas, miniature Ca2+ release events in terminals of hypothalamic neurons, are increased in frequency by depolarization in the absence of Ca2+ influx. J Neurosci. 2004 Feb 4; 24(5):1226-35.
          View in: PubMed
        38. O'Reilly CM, Fogarty KE, Drummond RM, Tuft RA, Walsh JV. Spontaneous mitochondrial depolarizations are independent of SR Ca2+ release. Am J Physiol Cell Physiol. 2004 May; 286(5):C1139-51.
          View in: PubMed
        39. O'Reilly CM, Fogarty KE, Drummond RM, Tuft RA, Walsh JV. Quantitative analysis of spontaneous mitochondrial depolarizations. Biophys J. 2003 Nov; 85(5):3350-7.
          View in: PubMed
        40. Hayakawa A, Hayes SJ, Lawe DC, Sudharshan E, Tuft R, Fogarty K, Lambright D, Corvera S. Structural basis for endosomal targeting by FYVE domains. J Biol Chem. 2004 Feb 13; 279(7):5958-66.
          View in: PubMed
        41. Lawe DC, Sitouah N, Hayes S, Chawla A, Virbasius JV, Tuft R, Fogarty K, Lifshitz L, Lambright D, Corvera S. Essential role of Ca2+/calmodulin in Early Endosome Antigen-1 localization. Mol Biol Cell. 2003 Jul; 14(7):2935-45.
          View in: PubMed
        42. Femino AM, Fogarty K, Lifshitz LM, Carrington W, Singer RH. Visualization of single molecules of mRNA in situ. Methods Enzymol. 2003; 361:245-304.
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        43. Rapizzi E, Pinton P, Szabadkai G, Wieckowski MR, Vandecasteele G, Baird G, Tuft RA, Fogarty KE, Rizzuto R. Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria. J Cell Biol. 2002 Nov 25; 159(4):613-24.
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        44. Zhuge R, Fogarty KE, Tuft RA, Walsh JV. Spontaneous transient outward currents arise from microdomains where BK channels are exposed to a mean Ca(2+) concentration on the order of 10 microM during a Ca(2+) spark. J Gen Physiol. 2002 Jul; 120(1):15-27.
          View in: PubMed
        45. Zou H, Lifshitz LM, Tuft RA, Fogarty KE, Singer JJ. Visualization of Ca2+ entry through single stretch-activated cation channels. Proc Natl Acad Sci U S A. 2002 Apr 30; 99(9):6404-9.
          View in: PubMed
        46. Kidd JF, Pilkington MF, Schell MJ, Fogarty KE, Skepper JN, Taylor CW, Thorn P. Paclitaxel affects cytosolic calcium signals by opening the mitochondrial permeability transition pore. J Biol Chem. 2002 Feb 22; 277(8):6504-10.
          View in: PubMed
        47. Lawe DC, Chawla A, Merithew E, Dumas J, Carrington W, Fogarty K, Lifshitz L, Tuft R, Lambright D, Corvera S. Sequential roles for phosphatidylinositol 3-phosphate and Rab5 in tethering and fusion of early endosomes via their interaction with EEA1. J Biol Chem. 2002 Mar 8; 277(10):8611-7.
          View in: PubMed
        48. Grigg A, Hoffman AH, Fogarty KE. Properties of Golgi-Mazzoni afferents in cat knee joint capsule, as revealed by mechanical studies of isolated joint capsule. J Neurophysiol. 1982 Jan; 47(1):31-40.
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        49. Grigg P, Harrigan EP, Fogarty KE. Segmental reflexes mediated by joint afferent neurons in cat knee. J Neurophysiol. 1978 Jan; 41(1):9-14.
          View in: PubMed
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