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Robert Shenkar

TitleResearch Associate Professor
InstitutionUniversity of Chicago
DepartmentSurgery-Neurosurgery
AddressChicago IL 60637
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    Collapse Overview 
    Collapse overview
    1. Focus on signaling and therapy in cerebral cavernous malformations.
    2. Focus on biomarkers of cerebral cavernous malformations.
    3. Focus on inflammation in cerebral cavernous malformations.

    Several approaches are being used to conduct research on cerebral cavernous malformations, including murine models, magnetic resonance imaging, electron microscopy and confocal microscopy.

    Disease of Interest:

    Cerebral cavernous malformation (CCM) is a vascular disorder of the brain affecting 0.5% of the population. CCM disease can either be sporadic or familial, resulting from haploinsufficiency in one of three genes, KRIT1/CCM1, CCM2 or PDCD10/CCM3. Symptoms are CCM disease include seizures, neurological deficits and/or hemorrhagic stroke. There is presently no therapy to prevent the development or clinical progression of CCM lesions.

    Current Projects:

    1. ROCK Inhibition as Therapy for Cerebral Cavernous Malformation: We have shown that the loss of CCM proteins, KRIT1, CCM2 or PDCD10 activates RhoA and its downstream effector Rho kinase (ROCK). Increased vascular permeability in Krit1 and Ccm2 heterozygous mice is reversed by ROCK inhibition. ROCK activity is increased in human and mouse CCM endothelium. These observations led us to hypothesize that aberrant Rho activation causes CCM pathogenesis. We are currently conducting a cross sectional study on the effects of ROCK inhibition on CCM lesion burden. We are presently treating three CCM murine models (Krit1, Ccm2, Pdcd10) with the specific ROCK inhibitor fasudil, and the more pleiotropic ROCK inhibitors simvastatin and atorvastatin. After therapy, we are assessing the mouse brains for lesion burden, lesion area, iron deposition, inflammation, ultrastructure and endothelial junctional protein expression. In longitudinal studies we examine CCM lesions for growth and size, iron deposition and phenotypic markers after therapy in murine models after they are identified by magnetic resonance imaging in vivo, and the effects of therapy will be evaluated mechanistically through differential gene expression. Surgically resected human CCM lesions will be examined for differential expression and signaling pathways for ROCK related genes.

    2. Biomarkers of Brain Permeability in Human Cerebral Cavernous Malformations: Our observations on the relationship between CCM proteins, endothelial permeability and ROCK activity suggest that both endothelial permeability and ROCK activity could be used as biomarkers for CCM disease. We are currently measuring vascular permeability in the brains of patients with CCM disease by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging. Because ROCK activity in leukocytes was shown to decrease by statins by our collaborator, Dr. James Liao, we are using leukocyte ROCK activity as a biomarker in patients with CCM disease. These techniques will allow us to assess brain vascular permeability and leukocyte ROCK activity as potential biomarkers for CCM disease severity in patients.

    3. Inflammation in Cerebral Cavernous Malformation: My observation that immunoglobulins were among the most highly expressed genes in surgically resected human cerebral cavernous malformations, led our laboratory to show a robust presence of B, T and plasma cells in CCM lesions both from patients and murine models, and immune complexes in human lesions. Immunoglobulins from plasma cells in human CCM lesions were shown to be oligoclonal. The immunoglobulin variable region RNA isolated from plasma cells from human CCM lesions was sequenced and used to make recombinant antibodies, which may be used to identify the triggering antigen. We are presently pursuing the effect of B depletion on CCM lesions in murine models.


    Collapse Biography 
    Collapse education and training
    University of Colorado, Denver, COPostdoctoral Fellow1995Pulmonary and Critical Care Medicine
    University of California, Los Angeles, CAPostdoctoral Fellow1993Pulmonary
    University of Southern California, Los Angeles, CAPostcoctoral Fellow1992Molecular Biology
    Cornell University Medical Center, New York, NYPostdoctoral Trainee1986Medicine
    Rockefeller University, New York, NYPostdoctoral Trainee1986Investigative Dermatology
    University of Chicago, Chicago, ILPostdoctoral Trainnee1983Microbiology
    University of California, Davis, CAPostdoctoral Research Geneticist1982Genetics
    Michigan State University, East Lansing, MIPhD1979Biophysics
    The University of Michigan, Ann Arbor, MIBS1974Biophysics

    Collapse ORNG Applications 
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    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Hong CC, Tang AT, Detter MR, Choi JP, Wang R, Yang X, Guerrero AA, Wittig CF, Hobson N, Girard R, Lightle R, Moore T, Shenkar R, Polster SP, Goddard LM, Ren AA, Leu NA, Sterling S, Yang J, Li L, Chen M, Mericko-Ishizuka P, Dow LE, Watanabe H, Schwaninger M, Min W, Marchuk DA, Zheng X, Awad IA, Kahn ML. Cerebral cavernous malformations are driven by ADAMTS5 proteolysis of versican. J Exp Med. 2020 Oct 05; 217(10). PMID: 32648916.
      View in: PubMed
    2. Detter MR, Shenkar R, Benavides CR, Neilson CA, Moore T, Lightle R, Hobson N, Shen L, Cao Y, Girard R, Zhang D, Griffin E, Gallione CJ, Awad IA, Marchuk DA. Novel Murine Models of Cerebral Cavernous Malformations. Angiogenesis. 2020 Jul 24. PMID: 32710309.
      View in: PubMed
    3. Koskimäki J, Polster SP, Li Y, Romanos S, Srinath A, Zhang D, Carrión-Penagos J, Lightle R, Moore T, Lyne SB, Stadnik A, Piedad K, Cao Y, Shenkar R, Dimov AV, Hobson N, Christoforidis GA, Carroll T, Girard R, Awad IA. Common transcriptome, plasma molecules, and imaging signatures in the aging brain and a Mendelian neurovascular disease, cerebral cavernous malformation. Geroscience. 2020 Jun 17. PMID: 32556941.
      View in: PubMed
    4. Polster SP, Sharma A, Tanes C, Tang AT, Mericko P, Cao Y, Carrión-Penagos J, Girard R, Koskimäki J, Zhang D, Stadnik A, Romanos SG, Lyne SB, Shenkar R, Yan K, Lee C, Akers A, Morrison L, Robinson M, Zafar A, Bittinger K, Kim H, Gilbert JA, Kahn ML, Shen L, Awad IA. Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma. Nat Commun. 2020 05 27; 11(1):2659. PMID: 32461638.
      View in: PubMed
    5. Zhang D, Kinloch AJ, Srinath A, Shenkar R, Girard R, Lightle R, Moore T, Koskimäki J, Mohsin A, Carrión-Penagos J, Romanos S, Shen L, Clark MR, Shi C, Awad IA. Antibodies in cerebral cavernous malformations react with cytoskeleton autoantigens in the lesional milieu. J Autoimmun. 2020 Apr 30; 102469. PMID: 32362501.
      View in: PubMed
    6. Carrión-Penagos J, Zeineddine HA, Polster SP, Girard R, Lyne SB, Koskimäki J, Romanos S, Srinath A, Zhang D, Cao Y, Stadnik A, Piedad K, Shenkar R, Awad IA. Subclinical imaging changes in cerebral cavernous angiomas during prospective surveillance. J Neurosurg. 2020 Apr 03; 1-8. PMID: 32244216.
      View in: PubMed
    7. Polster SP, Stadnik A, Akers AL, Cao Y, Christoforidis GA, Fam MD, Flemming KD, Girard R, Hobson N, Koenig JI, Koskimäki J, Lane K, Liao JK, Lee C, Lyne SB, McBee N, Morrison L, Piedad K, Shenkar R, Sorrentino M, Thompson RE, Whitehead KJ, Zeineddine HA, Hanley DF, Awad IA. Atorvastatin Treatment of Cavernous Angiomas with Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial. Neurosurgery. 2019 12 01; 85(6):843-853. PMID: 30476251.
      View in: PubMed
    8. Tang AT, Sullivan KR, Hong CC, Goddard LM, Mahadevan A, Ren A, Pardo H, Peiper A, Griffin E, Tanes C, Mattei LM, Yang J, Li L, Mericko-Ishizuka P, Shen L, Hobson N, Girard R, Lightle R, Moore T, Shenkar R, Polster SP, Roedel CJ, Li N, Zhu Q, Whitehead KJ, Zheng X, Akers A, Morrison L, Kim H, Bittinger K, Lengner CJ, Schwaninger M, Velcich A, Augenlicht L, Abdelilah-Seyfried S, Min W, Marchuk DA, Awad IA, Kahn ML. Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation. Sci Transl Med. 2019 11 27; 11(520). PMID: 31776290.
      View in: PubMed
    9. Hobson N, Polster SP, Cao Y, Flemming K, Shu Y, Huston J, Gerrard CY, Selwyn R, Mabray M, Zafar A, Girard R, Carrión-Penagos J, Chen YF, Parrish T, Zhou XJ, Koenig JI, Shenkar R, Stadnik A, Koskimäki J, Dimov A, Turley D, Carroll T, Awad IA. Phantom validation of quantitative susceptibility and dynamic contrast-enhanced permeability MR sequences across instruments and sites. J Magn Reson Imaging. 2020 Apr; 51(4):1192-1199. PMID: 31515878.
      View in: PubMed
    10. McKerracher L, Shenkar R, Abbinanti M, Cao Y, Peiper A, Liao JK, Lightle R, Moore T, Hobson N, Gallione C, Ruschel J, Koskimäki J, Girard R, Rosen K, Marchuk DA, Awad IA. A Brain-Targeted Orally Available ROCK2 Inhibitor Benefits Mild and Aggressive Cavernous Angioma Disease. Transl Stroke Res. 2020 Jun; 11(3):365-376. PMID: 31446620.
      View in: PubMed
    11. Koskimäki J, Zhang D, Li Y, Saadat L, Moore T, Lightle R, Polster SP, Carrión-Penagos J, Lyne SB, Zeineddine HA, Shi C, Shenkar R, Romanos S, Avner K, Srinath A, Shen L, Detter MR, Snellings D, Cao Y, Lopez-Ramirez MA, Fonseca G, Tang AT, Faber P, Andrade J, Ginsberg M, Kahn ML, Marchuk DA, Girard R, Awad IA. Transcriptome clarifies mechanisms of lesion genesis versus progression in models of Ccm3 cerebral cavernous malformations. Acta Neuropathol Commun. 2019 08 19; 7(1):132. PMID: 31426861.
      View in: PubMed
    12. Lyne SB, Girard R, Koskimäki J, Zeineddine HA, Zhang D, Cao Y, Li Y, Stadnik A, Moore T, Lightle R, Shi C, Shenkar R, Carrión-Penagos J, Polster SP, Romanos S, Akers A, Lopez-Ramirez M, Whitehead KJ, Kahn ML, Ginsberg MH, Marchuk DA, Awad IA. Biomarkers of cavernous angioma with symptomatic hemorrhage. JCI Insight. 2019 06 20; 4(12). PMID: 31217347.
      View in: PubMed
    13. Polster SP, Cao Y, Carroll T, Flemming K, Girard R, Hanley D, Hobson N, Kim H, Koenig J, Koskimäki J, Lane K, Majersik JJ, McBee N, Morrison L, Shenkar R, Stadnik A, Thompson RE, Zabramski J, Zeineddine HA, Awad IA. Trial Readiness in Cavernous Angiomas With Symptomatic Hemorrhage (CASH). Neurosurgery. 2019 04 01; 84(4):954-964. PMID: 29660039.
      View in: PubMed
    14. Shenkar R, Peiper A, Pardo H, Moore T, Lightle R, Girard R, Hobson N, Polster SP, Koskimäki J, Zhang D, Lyne SB, Cao Y, Chaudagar K, Saadat L, Gallione C, Pytel P, Liao JK, Marchuk D, Awad IA. Rho Kinase Inhibition Blunts Lesion Development and Hemorrhage in Murine Models of Aggressive Pdcd10/Ccm3 Disease. Stroke. 2019 03; 50(3):738-744. PMID: 30744543.
      View in: PubMed
    15. Zeineddine HA, Girard R, Saadat L, Shen L, Lightle R, Moore T, Cao Y, Hobson N, Shenkar R, Avner K, Chaudager K, Koskimäki J, Polster SP, Fam MD, Shi C, Lopez-Ramirez MA, Tang AT, Gallione C, Kahn ML, Ginsberg M, Marchuk DA, Awad IA. Phenotypic characterization of murine models of cerebral cavernous malformations. Lab Invest. 2019 03; 99(3):319-330. PMID: 29946133.
      View in: PubMed
    16. Girard R, Zeineddine HA, Koskimäki J, Fam MD, Cao Y, Shi C, Moore T, Lightle R, Stadnik A, Chaudagar K, Polster S, Shenkar R, Duggan R, Leclerc D, Whitehead KJ, Li DY, Awad IA. Plasma Biomarkers of Inflammation and Angiogenesis Predict Cerebral Cavernous Malformation Symptomatic Hemorrhage or Lesional Growth. Circ Res. 2018 06 08; 122(12):1716-1721. PMID: 29720384.
      View in: PubMed
    17. Lopez-Ramirez MA, Fonseca G, Zeineddine HA, Girard R, Moore T, Pham A, Cao Y, Shenkar R, de Kreuk BJ, Lagarrigue F, Lawler J, Glass CK, Awad IA, Ginsberg MH. Thrombospondin1 (TSP1) replacement prevents cerebral cavernous malformations. J Exp Med. 2017 Nov 06; 214(11):3331-3346. PMID: 28970240.
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    18. Girard R, Zeineddine HA, Fam MD, Mayampurath A, Cao Y, Shi C, Shenkar R, Polster SP, Jesselson M, Duggan R, Mikati AG, Christoforidis G, Andrade J, Whitehead KJ, Li DY, Awad IA. Plasma Biomarkers of Inflammation Reflect Seizures and Hemorrhagic Activity of Cerebral Cavernous Malformations. Transl Stroke Res. 2018 02; 9(1):34-43. PMID: 28819935.
      View in: PubMed
    19. Zeineddine HA, Girard R, Cao Y, Hobson N, Fam MD, Stadnik A, Tan H, Shen J, Chaudagar K, Shenkar R, Thompson RE, McBee N, Hanley D, Carroll T, Christoforidis GA, Awad IA. Quantitative susceptibility mapping as a monitoring biomarker in cerebral cavernous malformations with recent hemorrhage. J Magn Reson Imaging. 2018 04; 47(4):1133-1138. PMID: 28791783.
      View in: PubMed
    20. Shenkar R, Shi C, Austin C, Moore T, Lightle R, Cao Y, Zhang L, Wu M, Zeineddine HA, Girard R, McDonald DA, Rorrer A, Gallione C, Pytel P, Liao JK, Marchuk DA, Awad IA. RhoA Kinase Inhibition With Fasudil Versus Simvastatin in Murine Models of Cerebral Cavernous Malformations. Stroke. 2017 01; 48(1):187-194. PMID: 27879448.
      View in: PubMed
    21. Girard R, Fam MD, Zeineddine HA, Tan H, Mikati AG, Shi C, Jesselson M, Shenkar R, Wu M, Cao Y, Hobson N, Larsson HBW, Christoforidis GA, Awad IA. Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations. J Neurosurg. 2017 Jul; 127(1):102-110. PMID: 27494817.
      View in: PubMed
    22. Girard R, Zeineddine HA, Orsbon C, Tan H, Moore T, Hobson N, Shenkar R, Lightle R, Shi C, Fam MD, Cao Y, Shen L, Neander AI, Rorrer A, Gallione C, Tang AT, Kahn ML, Marchuk DA, Luo ZX, Awad IA. Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease. J Neurosci Methods. 2016 09 15; 271:14-24. PMID: 27345427.
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    23. Zhou Z, Tang AT, Wong WY, Bamezai S, Goddard LM, Shenkar R, Zhou S, Yang J, Wright AC, Foley M, Arthur JS, Whitehead KJ, Awad IA, Li DY, Zheng X, Kahn ML. Corrigendum: Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling. Nature. 2016 08 25; 536(7617):488. PMID: 27281211.
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    24. Zhou Z, Tang AT, Wong WY, Bamezai S, Goddard LM, Shenkar R, Zhou S, Yang J, Wright AC, Foley M, Arthur JS, Whitehead KJ, Awad IA, Li DY, Zheng X, Kahn ML. Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling. Nature. 2016 Apr 07; 532(7597):122-6. PMID: 27027284.
      View in: PubMed
    25. Girard R, Khanna O, Shenkar R, Zhang L, Wu M, Jesselson M, Zeineddine HA, Gangal A, Fam MD, Gibson CC, Whitehead KJ, Li DY, Liao JK, Shi C, Awad IA. Peripheral plasma vitamin D and non-HDL cholesterol reflect the severity of cerebral cavernous malformation disease. Biomark Med. 2016; 10(3):255-64. PMID: 26861901.
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    26. Mikati AG, Khanna O, Zhang L, Girard R, Shenkar R, Guo X, Shah A, Larsson HB, Tan H, Li L, Wishnoff MS, Shi C, Christoforidis GA, Awad IA. Vascular permeability in cerebral cavernous malformations. J Cereb Blood Flow Metab. 2015 Oct; 35(10):1632-9. PMID: 25966944.
      View in: PubMed
    27. Shenkar R, Shi C, Rebeiz T, Stockton RA, McDonald DA, Mikati AG, Zhang L, Austin C, Akers AL, Gallione CJ, Rorrer A, Gunel M, Min W, De Souza JM, Lee C, Marchuk DA, Awad IA. Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations. Genet Med. 2015 Mar; 17(3):188-196. PMID: 25122144.
      View in: PubMed
    28. Tan H, Liu T, Wu Y, Thacker J, Shenkar R, Mikati AG, Shi C, Dykstra C, Wang Y, Prasad PV, Edelman RR, Awad IA. Evaluation of iron content in human cerebral cavernous malformation using quantitative susceptibility mapping. Invest Radiol. 2014 Jul; 49(7):498-504. PMID: 24619210.
      View in: PubMed
    29. Shi C, Shenkar R, Kinloch A, Henderson SG, Shaaya M, Chong AS, Clark MR, Awad IA. Immune complex formation and in situ B-cell clonal expansion in human cerebral cavernous malformations. J Neuroimmunol. 2014 Jul 15; 272(1-2):67-75. PMID: 24864012.
      View in: PubMed
    30. Mikati AG, Tan H, Shenkar R, Li L, Zhang L, Guo X, Larsson HB, Shi C, Liu T, Wang Y, Shah A, Edelman RR, Christoforidis G, Awad I. Dynamic permeability and quantitative susceptibility: related imaging biomarkers in cerebral cavernous malformations. Stroke. 2014 Feb; 45(2):598-601. PMID: 24302484.
      View in: PubMed
    31. McDonald DA, Shi C, Shenkar R, Stockton RA, Liu F, Ginsberg MH, Marchuk DA, Awad IA. Fasudil decreases lesion burden in a murine model of cerebral cavernous malformation disease. Stroke. 2012 Feb; 43(2):571-4. PMID: 22034008.
      View in: PubMed
    32. McDonald DA, Shenkar R, Shi C, Stockton RA, Akers AL, Kucherlapati MH, Kucherlapati R, Brainer J, Ginsberg MH, Awad IA, Marchuk DA. A novel mouse model of cerebral cavernous malformations based on the two-hit mutation hypothesis recapitulates the human disease. Hum Mol Genet. 2011 Jan 15; 20(2):211-22. PMID: 20940147.
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    33. Yadla S, Jabbour PM, Shenkar R, Shi C, Campbell PG, Awad IA. Cerebral cavernous malformations as a disease of vascular permeability: from bench to bedside with caution. Neurosurg Focus. 2010 Sep; 29(3):E4. PMID: 20809762.
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    34. Stockton RA, Shenkar R, Awad IA, Ginsberg MH. Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity. J Exp Med. 2010 Apr 12; 207(4):881-96. PMID: 20308363.
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    35. Gault J, Awad IA, Recksiek P, Shenkar R, Breeze R, Handler M, Kleinschmidt-DeMasters BK. Cerebral cavernous malformations: somatic mutations in vascular endothelial cells. Neurosurgery. 2009 Jul; 65(1):138-44; discussion 144-5. PMID: 19574835.
      View in: PubMed
    36. Shi C, Shenkar R, Du H, Duckworth E, Raja H, Batjer HH, Awad IA. Immune response in human cerebral cavernous malformations. Stroke. 2009 May; 40(5):1659-65. PMID: 19286587.
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    37. Shi C, Awad IA, Jafari N, Lin S, Du P, Hage ZA, Shenkar R, Getch CC, Bredel M, Batjer HH, Bendok BR. Genomics of human intracranial aneurysm wall. Stroke. 2009 Apr; 40(4):1252-61. PMID: 19228845.
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    38. Shenkar R, Venkatasubramanian PN, Zhao JC, Batjer HH, Wyrwicz AM, Awad IA. Advanced magnetic resonance imaging of cerebral cavernous malformations: part I. High-field imaging of excised human lesions. Neurosurgery. 2008 Oct; 63(4):782-9; discussion 789. PMID: 18981890.
      View in: PubMed
    39. Shenkar R, Venkatasubramanian PN, Wyrwicz AM, Zhao JC, Shi C, Akers A, Marchuk DA, Awad IA. Advanced magnetic resonance imaging of cerebral cavernous malformations: part II. Imaging of lesions in murine models. Neurosurgery. 2008 Oct; 63(4):790-7; discussion 797-8. PMID: 18981891.
      View in: PubMed
    40. Shi C, Shenkar R, Batjer HH, Check IJ, Awad IA. Oligoclonal immune response in cerebral cavernous malformations. Laboratory investigation. J Neurosurg. 2007 Nov; 107(5):1023-6. PMID: 17977276.
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    41. Shenkar R, Shi C, Check IJ, Lipton HL, Awad IA. Concepts and hypotheses: inflammatory hypothesis in the pathogenesis of cerebral cavernous malformations. Neurosurgery. 2007 Oct; 61(4):693-702; discussion 702-3. PMID: 17986930.
      View in: PubMed
    42. Mindea SA, Yang BP, Shenkar R, Bendok B, Batjer HH, Awad IA. Cerebral cavernous malformations: clinical insights from genetic studies. Neurosurg Focus. 2006 Jul 15; 21(1):e1. PMID: 16859247.
      View in: PubMed
    43. Gault J, Shenkar R, Recksiek P, Awad IA. Biallelic somatic and germ line CCM1 truncating mutations in a cerebral cavernous malformation lesion. Stroke. 2005 Apr; 36(4):872-4. PMID: 15718512.
      View in: PubMed
    44. Shenkar R, Sarin H, Awadallah NA, Gault J, Kleinschmidt-DeMasters BK, Awad IA. Variations in structural protein expression and endothelial cell proliferation in relation to clinical manifestations of cerebral cavernous malformations. Neurosurgery. 2005 Feb; 56(2):343-54. PMID: 15670382.
      View in: PubMed
    45. Gault J, Sarin H, Awadallah NA, Shenkar R, Awad IA. Pathobiology of human cerebrovascular malformations: basic mechanisms and clinical relevance. Neurosurgery. 2004 Jul; 55(1):1-16; discussion 16-7. PMID: 15214969.
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    46. Meldrum DR, Partrick DA, Cleveland JC, Shenkar R, Meldrum KK, Raiesdana A, Ayala A, Brown JW, Harken AH. On-pump coronary artery bypass surgery activates human myocardial NF-kappaB and increases TNF-alpha in the heart. J Surg Res. 2003 Jun 15; 112(2):175-9. PMID: 12888335.
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    47. Shenkar R, Elliott JP, Diener K, Gault J, Hu LJ, Cohrs RJ, Phang T, Hunter L, Breeze RE, Awad IA. Differential gene expression in human cerebrovascular malformations. Neurosurgery. 2003 Feb; 52(2):465-77; discussion 477-8. PMID: 12535382.
      View in: PubMed
    48. Arcaroli J, Kupfner J, Yum HK, Shenkar R, Park JS, Abraham E. Lipopolysaccharide-induced neutrophil gene expression under in vivo or in vitro conditions. Chest. 2002 Mar; 121(3 Suppl):76S. PMID: 11893694.
      View in: PubMed
    49. Yum HK, Arcaroli J, Kupfner J, Shenkar R, Penninger JM, Sasaki T, Yang KY, Park JS, Abraham E. Involvement of phosphoinositide 3-kinases in neutrophil activation and the development of acute lung injury. J Immunol. 2001 Dec 01; 167(11):6601-8. PMID: 11714830.
      View in: PubMed
    50. Shenkar R, Yum HK, Arcaroli J, Kupfner J, Abraham E. Interactions between CBP, NF-kappaB, and CREB in the lungs after hemorrhage and endotoxemia. Am J Physiol Lung Cell Mol Physiol. 2001 Aug; 281(2):L418-26. PMID: 11435217.
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    51. Abraham E, Arcaroli J, Shenkar R. Activation of extracellular signal-regulated kinases, NF-kappa B, and cyclic adenosine 5'-monophosphate response element-binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia. J Immunol. 2001 Jan 01; 166(1):522-30. PMID: 11123332.
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    52. Abraham E, Carmody A, Shenkar R, Arcaroli J. Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2000 Dec; 279(6):L1137-45. PMID: 11076804.
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    53. Donnahoo KK, Meldrum DR, Shenkar R, Chung CS, Abraham E, Harken AH. Early renal ischemia, with or without reperfusion, activates NFkappaB and increases TNF-alpha bioactivity in the kidney. J Urol. 2000 Apr; 163(4):1328-32. PMID: 10737538.
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    54. Moine P, McIntyre R, Schwartz MD, Kaneko D, Shenkar R, Le Tulzo Y, Moore EE, Abraham E. NF-kappaB regulatory mechanisms in alveolar macrophages from patients with acute respiratory distress syndrome. Shock. 2000 Feb; 13(2):85-91. PMID: 10670837.
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    55. Shenkar R, Abraham E. Mechanisms of lung neutrophil activation after hemorrhage or endotoxemia: roles of reactive oxygen intermediates, NF-kappa B, and cyclic AMP response element binding protein. J Immunol. 1999 Jul 15; 163(2):954-62. PMID: 10395692.
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    56. Parsey MV, Kaneko D, Shenkar R, Abraham E. Neutrophil apoptosis in the lung after hemorrhage or endotoxemia: apoptosis and migration are independent of interleukin-1beta. Chest. 1999 Jul; 116(1 Suppl):67S-68S. PMID: 10424597.
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    57. Abraham E, Kaneko DJ, Shenkar R. Effects of endogenous and exogenous catecholamines on LPS-induced neutrophil trafficking and activation. Am J Physiol. 1999 01; 276(1):L1-8. PMID: 9887049.
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    58. Meldrum DR, Shenkar R, Sheridan BC, Cain BS, Abraham E, Harken AH. Hemorrhage activates myocardial NFkappaB and increases TNF-alpha in the heart. J Mol Cell Cardiol. 1997 Oct; 29(10):2849-54. PMID: 9344778.
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    59. Moine P, Shenkar R, Kaneko D, Le Tulzo Y, Abraham E. Systemic blood loss affects NF-kappa B regulatory mechanisms in the lungs. Am J Physiol. 1997 Jul; 273(1 Pt 1):L185-92. PMID: 9252555.
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    60. Le Tulzo Y, Shenkar R, Kaneko D, Moine P, Fantuzzi G, Dinarello CA, Abraham E. Hemorrhage increases cytokine expression in lung mononuclear cells in mice: involvement of catecholamines in nuclear factor-kappaB regulation and cytokine expression. J Clin Invest. 1997 Apr 01; 99(7):1516-24. PMID: 9119995.
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    61. Shenkar R, Abraham E. Hemorrhage induces rapid in vivo activation of CREB and NF-kappaB in murine intraparenchymal lung mononuclear cells. Am J Respir Cell Mol Biol. 1997 Feb; 16(2):145-52. PMID: 9032121.
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    62. Shea LM, Beehler C, Schwartz M, Shenkar R, Tuder R, Abraham E. Hyperoxia activates NF-kappaB and increases TNF-alpha and IFN-gamma gene expression in mouse pulmonary lymphocytes. J Immunol. 1996 Nov 01; 157(9):3902-8. PMID: 8892621.
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    63. Shenkar R, Navidi W, Tavaré S, Dang MH, Chomyn A, Attardi G, Cortopassi G, Arnheim N. The mutation rate of the human mtDNA deletion mtDNA4977. Am J Hum Genet. 1996 Oct; 59(4):772-80. PMID: 8808591.
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    64. Schwartz MD, Moore EE, Moore FA, Shenkar R, Moine P, Haenel JB, Abraham E. Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome. Crit Care Med. 1996 Aug; 24(8):1285-92. PMID: 8706481.
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    65. Shenkar R, Schwartz MD, Terada LS, Repine JE, McCord J, Abraham E. Hemorrhage activates NF-kappa B in murine lung mononuclear cells in vivo. Am J Physiol. 1996 May; 270(5 Pt 1):L729-35. PMID: 8967506.
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    66. Abraham E, Bursten S, Shenkar R, Allbee J, Tuder R, Woodson P, Guidot DM, Rice G, Singer JW, Repine JE. Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice. J Exp Med. 1995 Feb 01; 181(2):569-75. PMID: 7836912.
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    67. Shenkar R, Cohen AJ, Vestweber D, Miller YE, Tuder R, Abraham E. Hemorrhage and resuscitation alter the expression of ICAM-1 and P-selectin in mice. J Inflamm. 1995; 45(4):248-59. PMID: 8867669.
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    68. Shenkar R, Abraham E. Effects of treatment with the 21-aminosteroid, U7438F, on pulmonary cytokine expression following hemorrhage and resuscitation. Crit Care Med. 1995 Jan; 23(1):132-9. PMID: 8001365.
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    69. Shenkar R, Coulson WF, Abraham E. Anti-transforming growth factor-beta monoclonal antibodies prevent lung injury in hemorrhaged mice. Am J Respir Cell Mol Biol. 1994 Sep; 11(3):351-7. PMID: 8086171.
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    70. Shenkar R, Coulson WF, Abraham E. Hemorrhage and resuscitation induce alterations in cytokine expression and the development of acute lung injury. Am J Respir Cell Mol Biol. 1994 Mar; 10(3):290-7. PMID: 8117448.
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    71. Shenkar R, Chang YH, Abraham E. Cytokine expression in Peyer's patches following hemorrhage and resuscitation. Shock. 1994 Jan; 1(1):25-30. PMID: 7538033.
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    72. Ling X, Shenkar R, Sakai D, Arnheim N. The mouse Eb meiotic recombination hotspot contains a tissue-specific transcriptional enhancer. Immunogenetics. 1993; 37(5):331-6. PMID: 8428766.
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    73. Shenkar R, Shen MH, Arnheim N. DNase I-hypersensitive sites and transcription factor-binding motifs within the mouse E beta meiotic recombination hot spot. Mol Cell Biol. 1991 Apr; 11(4):1813-9. PMID: 1900917.
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    74. Banga SS, Shenkar R, Boyd JB. Hypersensitivity of Drosophila mei-41 mutants to hydroxyurea is associated with reduced mitotic chromosome stability. Mutat Res. 1986 Nov; 163(2):157-65. PMID: 3093854.
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    75. Strauss B, Larson K, Rabkin S, Sagher D, Sahm J, Shenkar R. In vitro models for mutagenesis: a role for lesion, polymerase and sequence. Prog Clin Biol Res. 1986; 209A:149-59. PMID: 3529104.
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    76. Larson K, Sahm J, Shenkar R, Strauss B. Methylation-induced blocks to in vitro DNA replication. Mutat Res. 1985 Jun-Jul; 150(1-2):77-84. PMID: 4000169.
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    77. Strauss BS, Larson K, Sagher D, Rabkin S, Shenkar R, Sahm J. In vitro models of mutagenesis. Carcinog Compr Surv. 1985; 10:481-93. PMID: 4064014.
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