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Imaging-based Research

Jordan S. Orange, MD, PhD

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Professor of Pediatrics (Allergy/Immunology)
Department: Pediatrics

Contact information
Columbia University College of Physicians and Surgeons
New York-Presbyterian Morgan Stanley Children's Hospital
3959 Broadway
New York, NY 10032
Office: (212) 305-2934
Education:
A.B. (Biology)
Brown University, 1990.
Ph.D. (Pathobiology)
Brown University, 1996.
M.D.
Brown University, 1997.
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Description of Penn IMIG Expertise

Research:



Orange Reserach Photo Natural killer (NK) lymphocytes are critical to host defense both for surveillance of tumor cells as well as for control of viral infections. As members of the innate immune system, they do not undergo genetic recombination to attain specificity.  The foundations of NK cell activities and regulation lie at the interface between NK cells and cells with which they interact. Once a favorable balance between the ligation of activating and inhibiting receptors has been achieved, NK cells kill target cells by extruding secretory lysosomes. The dynamic structure at the NK/target cell interface is known as the NK cell immunologic synapse (NKIS).

The focus of work in the Orange laboratory is to better understand the formation, function and regulation of the NKIS.  Using cells from patients with Wiskott-Aldrich syndrome, a human disease featuring impaired cytoskeletal function, we have shown that the activating NKIS is actin-dependent. This is in contrast to the inhibitory NKIS, which is actin-independent. We have also identified sequential steps required for the creation of the activating NKIS and have demonstrated that actin reorganization precedes and is required for microtubule function at the synapse. Our most recent work has focused upon cytoskeletal events required for polarization of the microtubule organizing center and lytic granules to the NKIS, as well as the final translocation of lytic granules to the synaptic membrane.


Lab expertise and resources:



  • Quantitative confocal microscopy

  • Colocalization studies

  • Nuclear localization studies

  • Dynamic object tracking

  • Total internal reflection fluorescence microsopy

  • Imaging under flow stress


IMIG Collaborations:



  • Orange and Reiner: evaluation and measurement of asymmetry in immune cells




Lab members:


Orange Lab Members

Selected Publications

Rak GD, Mace EM, Banerjee PP, Svitkina T, Orange JS: Natural killer cell lytic granule secretion occurs through a pervasive actin network at the immune synapse. PLoS biology 9(9): 1001151, Sep 2011 Notes: Featured in Biophotonics.

Orange JS, Roy-Ghanta S, Mace EM, Maru S, Rak GD, Sanborn KB, Fasth A, Saltzman R, Paisley A, Monaco-Shawver L, Banerjee PP, Pandey R: IL-2 induces a WAVE2-dependent pathway for actin reorganization that enables WASp-independent human NK cell function. J Clin Invest 121(4): 1535-48, Apr 2011.

Pedroza LA, Kumar V, Sanborn KB, Mace EM, Niinikoski H, Nadeau K, Vasconcelos Dde M, Perez E, Jyonouchi S, Jyonouchi H, Banerjee PP, Ruuskanen O, Condino-Neto A, Orange JS: Autoimmune regulator (AIRE) contributes to Dectin-1-induced TNF-α production and complexes with caspase recruitment domain-containing protein 9 (CARD9), spleen tyrosine kinase (Syk), and Dectin-1. The Journal of allergy and clinical immunology 129(2): 464-72, Feb 2011.

Mentlik, A. N., Sanborn, K. B., Holzbaur, E. L., Orange, J. S.: Rapid lytic granule convergence to the MTOC in natural killer cells is dependent on dynein but not cytolytic commitment. Mol Biol Cell 21(13): 2241-56, July 2010.

Boztug K, Schmidt M, Schwarzer A, Banerjee PP, Díez IA, Dewey RA, Böhm M, Nowrouzi A, Ball CR, Glimm H, Naundorf S, Kühlcke K, Blasczyk R, Kondratenko I, Maródi L, Orange JS, von Kalle C, Klein C: Stem-cell gene therapy for the Wiskott-Aldrich syndrome. The New England Journal of Medicine 363(20): 1918-27, Nov 2010.

Orange, J.S. : Formation and function of the lytic NK cell immunological synapse. Nature Rev. Immunol. 8: 713-725, 2008.

Banerjee, PP, Pandey, R, Zheng, R, Suhoski, MM, Monaco-Shawver, L, Orange, JS: Cdc42-interacting protein-4 functionally links actin and microtubule networks at the cytolytic NK cell immunological synapse. Journal Of Experimental Medicine 204(10): 2305-2320, OCT 2007.

Chang, JT, Palanivel, VR, Kinjyo, I, Schambach, F, Intlekofer, AM, Banerjee, A, Longworth, SA, Vinup, KE, Mrass, P, Oliaro, J, Killeen, N, Orange, JS, Russell, SM, Weninger, W, Reiner, SL: Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315(5819): 1687-1691, MAR 2007.

Pandey, R, DeStephan, CM, Madge, LA, May, MJ, Orange, JS: NKp30 ligation induces rapid activation of the canonical NF-kappa B pathway in NK cells. Journal Of Immunology 179(11): 7385-7396, DEC 2007.

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Last updated: 07/29/2025
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