University of Pittsburgh Department of Cell Biology

  • Research

    Imaging Immunology.

    The driving forces behind my research are cutting edge optical imaging and their application to studying basic cell biologic processes in the immune system.

    Dendritic cells are ubiquitous throughout the body, their primary function is as 'danger' detectors, the cells take up antigens from exogenous agents, process and present the antigen on the surface of the cell. Once exposed to antigen the cells mature, and migrate through the lymphatic drainage system to the lymph node where they present the antigen to effector cells of the immune system (such as cytotoxic T lymphocytes). Recently we showed that rather than acting in isolation, the DCs are actually physically interconnected through a network of extremely small tubules which allows clonal activation of populations of cells rather than each cell acting independently. Essentially electrical connectivity between cells allows a single cell to activate several neighbors (over a distance of several hundred microns). These activated cells then migrate toward the signaling cell and take up and process antigen also. Once activated the cells loose their dendritic appearance prior to migrating through the lymphatics. Once at the lymph node they reassume their dendritic morphology. Our studies depend critically on an array of live cell imaging methods; ratiometric measures of calcium concentration, high resolution DIC, Live cell Confocal, Confocal, 2P methods These efforts are now being expanded to include the functional role of nantotubes in immune cross presentation.

  • Publications

    1. Medina Sanchez L, Siller M, Zeng Y, Brigleb PH, Sangani KA, Soto AS, Engl C, Laughlin CR, Rana M, Van Der Kraak L, Pandey SP, Bender MJ, Fitzgerald B, Hedden L, Fiske K, Taylor GM, Wright AP, Mehta ID, Rahman SA, Galipeau HJ, Mullett SJ, Gelhaus SL, Watkins SC, Bercik P, Nice TJ, Jabri B, Meisel M, Das J, Dermody TS, Verdú EF, Hinterleitner R. The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells.. Immunity. 2023 Jul 11;():. pii: S1074-7613(23)00279-0. doi: 10.1016/j.immuni.2023.06.022. PubMed PMID: 37478853;
    2. Hislop JJ, Alavi A, Song Q, Schoenberger RL, Keshavarz F K, LeGraw R, Velazquez JJ, Mokhtari T, Taheri MN, Rytel M, de Sousa Lopes SMC, Watkins SC, Stolz DB, Kiani S, Sozen B, Bar-Joseph Z, Ebrahimkhani M. Modelling Human Post-Implantation Development via Extra-Embryonic Niche Engineering.. bioRxiv. 2023 Jul 24;():. pii: 2023.06.15.545118. doi: 10.1101/2023.06.15.545118. PubMed PMID: 37398391;
    3. Maggiore JC, LeGraw R, Przepiorski A, Velazquez J, Chaney C, Streeter E, Silva-Barbosa A, Franks J, Hislop J, Hill A, Wu H, Pfister K, Howden SE, Watkins SC, Little M, Humphreys BD, Watson A, Stolz DB, Kiani S, Davidson AJ, Carroll TJ, Cleaver O, Sims-Lucas S, Ebrahimkhani MR, Hukriede NA. Genetically engineering endothelial niche in human kidney organoids enables multilineage maturation, vascularization and de novo cell types.. bioRxiv. 2023 May 30;():. pii: 2023.05.30.542848. doi: 10.1101/2023.05.30.542848. PubMed PMID: 37333155;
    4. Dar HH, Mikulska-Ruminska K, Tyurina YY, Luci DK, Yasgar A, Samovich SN, Kapralov AA, Souryavong AB, Tyurin VA, Amoscato AA, Epperly MW, Shurin GV, Standley M, Holman TR, St Croix CM, Watkins SC, VanDemark AP, Rana S, Zakharov AV, Simeonov A, Marugan J, Mallampalli RK, Wenzel SE, Greenberger JS, Rai G, Bayir H, Bahar I, Kagan VE. Discovering selective antiferroptotic inhibitors of the 15LOX/PEBP1 complex noninterfering with biosynthesis of lipid mediators.. Proc Natl Acad Sci U S A. 2023 Jun 20;120(25):e2218896120. doi: 10.1073/pnas.2218896120. PubMed PMID: 37327313;
    5. Lee PY, Schilpp H, Naylor N, Watkins SC, Yang B, Sigal IA. Instant polarized light microscopy pi (IPOLπ) for quantitative imaging of collagen architecture and dynamics in ocular tissues.. Opt Lasers Eng. 2023 Jul;166():. pii: 107594. doi: 10.1016/j.optlaseng.2023.107594. PubMed PMID: 37193214;
    6. Koppes EA, Johnson MA, Moresco JJ, Luppi P, Lewis DW, Stolz DB, Diedrich JK, Yates JR 3rd, Wek RC, Watkins SC, Gollin SM, Park HJ, Drain P, Nicholls RD. Insulin secretion deficits in a Prader-Willi syndrome β-cell model are associated with a concerted downregulation of multiple endoplasmic reticulum chaperones.. PLoS Genet. 2023 Apr;19(4):e1010710. doi: 10.1371/journal.pgen.1010710. PubMed PMID: 37068109;
    7. DeMoya RA, Forman-Rubinsky RE, Fontaine D, Shin J, Watkins SC, Lo C, Tsang M. Sin3a Associated Protein 130kDa, sap130, plays an evolutionary conserved role in zebrafish heart development.. bioRxiv. 2023 Mar 31;():. pii: 2023.03.30.534737. doi: 10.1101/2023.03.30.534737. PubMed PMID: 37034673;
    8. Jang S, Raja SJ, Roginskaya V, Schaich MA, Watkins SC, Van Houten B. UV-DDB stimulates the activity of SMUG1 during base excision repair of 5-hydroxymethyl-2\'-deoxyuridine moieties.. Nucleic Acids Res. 2023 Jun 9;51(10):4881-4898. doi: 10.1093/nar/gkad206. PubMed PMID: 36971122;
    9. Lee PY, Schilpp H, Naylor N, Watkins SC, Yang B, Sigal IA. Instant polarized light microscopy pi (IPOLπ) for quantitative imaging of collagen architecture and dynamics in ocular tissues.. bioRxiv. 2023 Feb 27;():. pii: 2023.01.29.526111. doi: 10.1101/2023.01.29.526111. PubMed PMID: 36778384;
    10. Henpita C, Vyas R, Healy CL, Kieu TL, Gurkar AU, Yousefzadeh MJ, Cui Y, Lu A, Angelini LA, O\'Kelly RD, McGowan SJ, Chandrasekhar S, Vanderpool RR, Hennessy-Wack D, Ross MA, Bachman TN, McTiernan C, Pillai SPS, Ladiges W, Lavasani M, Huard J, Beer-Stolz D, St Croix CM, Watkins SC, Robbins PD, Mora AL, Kelley EE, Wang Y, O\'Connell TD, Niedernhofer LJ. Loss of DNA repair mechanisms in cardiac myocytes induce dilated cardiomyopathy.. Aging Cell. 2023 Apr;22(4):e13782. doi: 10.1111/acel.13782. PubMed PMID: 36734200;
    11. Klimas A, Gallagher BR, Wijesekara P, Fekir S, DiBernardo EF, Cheng Z, Stolz DB, Cambi F, Watkins SC, Brody SL, Horani A, Barth AL, Moore CI, Ren X, Zhao Y. Magnify is a universal molecular anchoring strategy for expansion microscopy.. Nat Biotechnol. 2023 Jun;41(6):858-869. doi: 10.1038/s41587-022-01546-1. PubMed PMID: 36593399;
    12. Jang S, Kumar N, Schaich MA, Zhong Z, van Loon B, Watkins SC, Van Houten B. Cooperative interaction between AAG and UV-DDB in the removal of modified bases.. Nucleic Acids Res. 2022 Dec 9;50(22):12856-12871. doi: 10.1093/nar/gkac1145. PubMed PMID: 36511855;
    13. D\'Aiuto L, Caldwell JK, Wallace CT, Grams TR, Wesesky MA, Wood JA, Watkins SC, Kinchington PR, Bloom DC, Nimgaonkar VL. The Impaired Neurodevelopment of Human Neural Rosettes in HSV-1-Infected Early Brain Organoids.. Cells. 2022 Nov 9;11(22):. doi: 10.3390/cells11223539. PubMed PMID: 36428968;
    14. Verma M, Francis L, Lizama BN, Callio J, Fricklas G, Wang KZQ, Kaufman BA, D\'Aiuto L, Stolz DB, Watkins SC, Nimgaonkar VL, Soto-Gutierrez A, Goldstein A, Chu CT. iPSC-Derived Neurons from Patients with POLG Mutations Exhibit Decreased Mitochondrial Content and Dendrite Simplification.. Am J Pathol. 2023 Feb;193(2):201-212. doi: 10.1016/j.ajpath.2022.11.002. PubMed PMID: 36414085;
    15. Kaminski N, Wondisford AR, Kwon Y, Lynskey ML, Bhargava R, Barroso-González J, García-Expósito L, He B, Xu M, Mellacheruvu D, Watkins SC, Modesti M, Miller KM, Nesvizhskii AI, Zhang H, Sung P, O\'Sullivan RJ. RAD51AP1 regulates ALT-HDR through chromatin-directed homeostasis of TERRA.. Mol Cell. 2022 Nov 3;82(21):4001-4017.e7. doi: 10.1016/j.molcel.2022.09.025. PubMed PMID: 36265488;
    16. Wijesekara P, Yadav P, Perkins LA, Stolz DB, Franks JM, Watkins SC, Reinoso Jacome E, Brody SL, Horani A, Xu J, Barati Farimani A, Ren X. Engineering rotating apical-out airway organoid for assessing respiratory cilia motility.. iScience. 2022 Aug 19;25(8):104730. doi: 10.1016/j.isci.2022.104730. PubMed PMID: 35942088;
    17. Oghifobibi OA, Toader AE, Nicholas MA, Nelson BP, Alindogan NG, Wolf MS, Kline AE, Nouraie SM, Bondi CO, Iordanova B, Clark RS, Bayır H, Loughran PA, Watkins SC, St Croix CM, Kochanek PM, Vazquez AL, Manole MD. Resuscitation with epinephrine worsens cerebral capillary no-reflow after experimental pediatric cardiac arrest: An in vivo multiphoton microscopy evaluation.. J Cereb Blood Flow Metab. 2022 Dec;42(12):2255-2269. doi: 10.1177/0271678X221113022. PubMed PMID: 35854408;

     

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