Dr. Rahman's research interests are:
1) Signaling Mechanisms of Endothelial ICAM-1 Expression
2) Neutrophil-mediated Lung Injury.

They want to know how pro-inflammatory mediators such as thrombin and tumor necrosis factor alpha (TNF) mediate neutrophils (PMN) sequestration and emigration in the lung and thus induce lung vascular injury. In particular, they are interested in defining the critical signaling pathways mediating expression of intercellular adhesion molecule (CAM-1; CD54), an inducible endothelial adhesive protein that serves as a counter-receptor for ²2-integrins (CD11/CD18) present on the surface of leukocytes. Interaction of ICAM-1 with ²2-integrins enables PMN to adhere firmly and stably to the vascular endothelium, and to migrate across the endothelial barrier. PMN binding to endothelial cells by this mechanism contributes to the development of lung vascular injury and tissue edema.

Dr. Rahman uses multidisciplinary approaches ranging from cultured endothelial cells and in vivo mouse models with targeted gene deletions to molecular biology and lung physiology to address these questions of fundamental importance.

• Bijli KM, Fazal F, Rahman A. Regulation of Rela/p65 and Endothelial Cell Inflammation by Proline-Rich Tyrosine Kinase 2. Am J Respir Cell Mol Biol. 2012 Nov; 47(5):660-8.
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• Rahman A, Fazal F. Blocking NF-?B: An Inflammatory Issue. Proc Am Thorac Soc. 2011 Nov; 8(6):497-503.
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• Yang L, Chen G, Mohanty S, Scott G, Fazal F, Rahman A, Begum S, Hynes RO, Xu L. GPR56 Regulates VEGF production and angiogenesis during melanoma progression. Cancer Res. 2011 Aug 15; 71(16):5558-68.
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• Edirisinghe I, Arunachalam G, Wong C, Yao H, Rahman A, Phipps RP, Jin ZG, Rahman I. Cigarette-smoke-induced oxidative/nitrosative stress impairs VEGF- and fluid-shear-stress-mediated signaling in endothelial cells. Antioxid Redox Signal. 2010 Jun 15; 12(12):1355-69.
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• Fazal F, Bijli KM, Minhajuddin M, Rein T, Finkelstein JN, Rahman A. Essential role of cofilin-1 in regulating thrombin-induced RelA/p65 nuclear translocation and intercellular adhesion molecule 1 (ICAM-1) expression in endothelial cells. J Biol Chem. 2009 Jul 31; 284(31):21047-56.
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• Rahman A, Fazal F. Hug tightly and say goodbye: role of endothelial ICAM-1 in leukocyte transmigration. Antioxid Redox Signal. 2009 Apr; 11(4):823-39.
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• Minhajuddin M, Bijli KM, Fazal F, Sassano A, Nakayama KI, Hay N, Platanias LC, Rahman A. Protein kinase C-delta and phosphatidylinositol 3-kinase/Akt activate mammalian target of rapamycin to modulate NF-kappaB activation and intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells. J Biol Chem. 2009 Feb 13; 284(7):4052-61.
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• Bijli KM, Fazal F, Minhajuddin M, Rahman A. Activation of Syk by protein kinase C-delta regulates thrombin-induced intercellular adhesion molecule-1 expression in endothelial cells via tyrosine phosphorylation of RelA/p65. J Biol Chem. 2008 May 23; 283(21):14674-84.
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• Edirisinghe I, Yang SR, Yao H, Rajendrasozhan S, Caito S, Adenuga D, Wong C, Rahman A, Phipps RP, Jin ZG, Rahman I. VEGFR-2 inhibition augments cigarette smoke-induced oxidative stress and inflammatory responses leading to endothelial dysfunction. FASEB J. 2008 Jul; 22(7):2297-310.
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• Fazal F, Minhajuddin M, Bijli KM, McGrath JL, Rahman A. Evidence for actin cytoskeleton-dependent and -independent pathways for RelA/p65 nuclear translocation in endothelial cells. J Biol Chem. 2007 Feb 9; 282(6):3940-50.
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• Bijli KM, Minhajuddin M, Fazal F, O'Reilly MA, Platanias LC, Rahman A. c-Src interacts with and phosphorylates RelA/p65 to promote thrombin-induced ICAM-1 expression in endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2007 Feb; 292(2):L396-404.
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• Orrington-Myers J, Gao X, Kouklis P, Broman M, Rahman A, Vogel SM, Malik AB. Regulation of lung neutrophil recruitment by VE-cadherin. Am J Physiol Lung Cell Mol Physiol. 2006 Oct; 291(4):L764-71.
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• Staversky RJ, Vitiello PF, Gehen SC, Helt CE, Rahman A, Keng PC, O'Reilly MA. p21(Cip1/Waf1/Sdi1) protects against hyperoxia by maintaining expression of Bcl-X(L). Free Radic Biol Med. 2006 Aug 15; 41(4):601-9.
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• Frey RS, Gao X, Javaid K, Siddiqui SS, Rahman A, Malik AB. Phosphatidylinositol 3-kinase gamma signaling through protein kinase Czeta induces NADPH oxidase-mediated oxidant generation and NF-kappaB activation in endothelial cells. J Biol Chem. 2006 Jun 9; 281(23):16128-38.
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• Minhajuddin M, Fazal F, Bijli KM, Amin MR, Rahman A. Inhibition of mammalian target of rapamycin potentiates thrombin-induced intercellular adhesion molecule-1 expression by accelerating and stabilizing NF-kappa B activation in endothelial cells. J Immunol. 2005 May 1; 174(9):5823-9.
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• Anwar KN, Fazal F, Malik AB, Rahman A. RhoA/Rho-associated kinase pathway selectively regulates thrombin-induced intercellular adhesion molecule-1 expression in endothelial cells via activation of I kappa B kinase beta and phosphorylation of RelA/p65. J Immunol. 2004 Dec 1; 173(11):6965-72.
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• Rahman A, Anwar KN, Minhajuddin M, Bijli KM, Javaid K, True AL, Malik AB. cAMP targeting of p38 MAP kinase inhibits thrombin-induced NF-kappaB activation and ICAM-1 expression in endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2004 Nov; 287(5):L1017-24.
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• Paria BC, Malik AB, Kwiatek AM, Rahman A, May MJ, Ghosh S, Tiruppathi C. Tumor necrosis factor-alpha induces nuclear factor-kappaB-dependent TRPC1 expression in endothelial cells. J Biol Chem. 2003 Sep 26; 278(39):37195-203.
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• Deb DK, Sassano A, Lekmine F, Majchrzak B, Verma A, Kambhampati S, Uddin S, Rahman A, Fish EN, Platanias LC. Activation of protein kinase C delta by IFN-gamma. J Immunol. 2003 Jul 1; 171(1):267-73.
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• Ong ES, Gao XP, Xu N, Predescu D, Rahman A, Broman MT, Jho DH, Malik AB. E. coli pneumonia induces CD18-independent airway neutrophil migration in the absence of increased lung vascular permeability. Am J Physiol Lung Cell Mol Physiol. 2003 Oct; 285(4):L879-88.
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• Kambhampati S, Li Y, Verma A, Sassano A, Majchrzak B, Deb DK, Parmar S, Giafis N, Kalvakolanu DV, Rahman A, Uddin S, Minucci S, Tallman MS, Fish EN, Platanias LC. Activation of protein kinase C delta by all-trans-retinoic acid. J Biol Chem. 2003 Aug 29; 278(35):32544-51.
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• Babcock TA, Kurland A, Helton WS, Rahman A, Anwar KN, Espat NJ. Inhibition of activator protein-1 transcription factor activation by omega-3 fatty acid modulation of mitogen-activated protein kinase signaling kinases. JPEN J Parenter Enteral Nutr. 2003 May-Jun; 27(3):176-80; discussion 181.
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• Javaid K, Rahman A, Anwar KN, Frey RS, Minshall RD, Malik AB. Tumor necrosis factor-alpha induces early-onset endothelial adhesivity by protein kinase Czeta-dependent activation of intercellular adhesion molecule-1. Circ Res. 2003 May 30; 92(10):1089-97.
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• Rahman A, True AL, Anwar KN, Ye RD, Voyno-Yasenetskaya TA, Malik AB. Galpha(q) and Gbetagamma regulate PAR-1 signaling of thrombin-induced NF-kappaB activation and ICAM-1 transcription in endothelial cells. Circ Res. 2002 Sep 6; 91(5):398-405.
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• Skidgel RA, Gao XP, Brovkovych V, Rahman A, Jho D, Predescu S, Standiford TJ, Malik AB. Nitric oxide stimulates macrophage inflammatory protein-2 expression in sepsis. J Immunol. 2002 Aug 15; 169(4):2093-101.
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• Frey RS, Rahman A, Kefer JC, Minshall RD, Malik AB. PKCzeta regulates TNF-alpha-induced activation of NADPH oxidase in endothelial cells. Circ Res. 2002 May 17; 90(9):1012-9.
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• Gao XP, Standiford TJ, Rahman A, Newstead M, Holland SM, Dinauer MC, Liu QH, Malik AB. Role of NADPH oxidase in the mechanism of lung neutrophil sequestration and microvessel injury induced by Gram-negative sepsis: studies in p47phox-/- and gp91phox-/- mice. J Immunol. 2002 Apr 15; 168(8):3974-82.
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• Xu N, Gao XP, Minshall RD, Rahman A, Malik AB. Time-dependent reversal of sepsis-induced PMN uptake and lung vascular injury by expression of CD18 antagonist. Am J Physiol Lung Cell Mol Physiol. 2002 Apr; 282(4):L796-802.
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• Uddin S, Sassano A, Deb DK, Verma A, Majchrzak B, Rahman A, Malik AB, Fish EN, Platanias LC. Protein kinase C-delta (PKC-delta ) is activated by type I interferons and mediates phosphorylation of Stat1 on serine 727. J Biol Chem. 2002 Apr 26; 277(17):14408-16.
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• Fan J, Frey RS, Rahman A, Malik AB. Role of neutrophil NADPH oxidase in the mechanism of tumor necrosis factor-alpha -induced NF-kappa B activation and intercellular adhesion molecule-1 expression in endothelial cells. J Biol Chem. 2002 Feb 1; 277(5):3404-11.
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• Gao X, Xu N, Sekosan M, Mehta D, Ma SY, Rahman A, Malik AB. Differential role of CD18 integrins in mediating lung neutrophil sequestration and increased microvascular permeability induced by Escherichia coli in mice. J Immunol. 2001 Sep 1; 167(5):2895-901.
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• Rahman A, Anwar KN, Uddin S, Xu N, Ye RD, Platanias LC, Malik AB. Protein kinase C-delta regulates thrombin-induced ICAM-1 gene expression in endothelial cells via activation of p38 mitogen-activated protein kinase. Mol Cell Biol. 2001 Aug; 21(16):5554-65.
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• Yang M, Sang H, Rahman A, Wu D, Malik AB, Ye RD. G alpha 16 couples chemoattractant receptors to NF-kappa B activation. J Immunol. 2001 Jun 1; 166(11):6885-92.
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• Mehta D, Rahman A, Malik AB. Protein kinase C-alpha signals rho-guanine nucleotide dissociation inhibitor phosphorylation and rho activation and regulates the endothelial cell barrier function. J Biol Chem. 2001 Jun 22; 276(25):22614-20.
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• Kefer J, Rahman A, Anwar KN, Malik AB. Decreased oxidant buffering impairs NF-kappaB activation and ICAM-1 transcription in endothelial cells. Shock. 2001 Jan; 15(1):11-5.
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• Rahman A, Anwar KN, Malik AB. Protein kinase C-zeta mediates TNF-alpha-induced ICAM-1 gene transcription in endothelial cells. Am J Physiol Cell Physiol. 2000 Oct; 279(4):C906-14.
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• Xu N, Rahman A, Minshall RD, Tiruppathi C, Malik AB. beta(2)-Integrin blockade driven by E-selectin promoter prevents neutrophil sequestration and lung injury in mice. Circ Res. 2000 Aug 4; 87(3):254-60.
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• Lo SK, Rahman A, Xu N, Zhou MY, Nagpala P, Jaffe HA, Malik AB. Neutrophil inhibitory factor abrogates neutrophil adhesion by blockade of CD11a and CD11b beta(2) integrins. Mol Pharmacol. 1999 Nov; 56(5):926-32.
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• Rahman A, Anwar KN, True AL, Malik AB. Thrombin-induced p65 homodimer binding to downstream NF-kappa B site of the promoter mediates endothelial ICAM-1 expression and neutrophil adhesion. J Immunol. 1999 May 1; 162(9):5466-76.
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• Rahman A, Bando M, Kefer J, Anwar KN, Malik AB. Protein kinase C-activated oxidant generation in endothelial cells signals intercellular adhesion molecule-1 gene transcription. Mol Pharmacol. 1999 Mar; 55(3):575-83.
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• Roebuck KA, Rahman A, Lakshminarayanan V, Janakidevi K, Malik AB. H2O2 and tumor necrosis factor-alpha activate intercellular adhesion molecule 1 (ICAM-1) gene transcription through distinct cis-regulatory elements within the ICAM-1 promoter. J Biol Chem. 1995 Aug 11; 270(32):18966-74.
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• Rahman A, Malhotra P, Dhar R, Kewalramani T, Thimmapaya B. Effect of single-base substitutions in the central domain of virus-associated RNA I on its function. J Virol. 1995 Jul; 69(7):4299-307.
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• Said Ahmad M, Fazal F, Rahman A, Hadi SM, Parish JH. Activities of flavonoids for the cleavage of DNA in the presence of Cu(II): correlation with generation of active oxygen species. Carcinogenesis. 1992 Apr; 13(4):605-8.
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• Rahman A, Fazal F, Greensill J, Ainley K, Parish JH, Hadi SM. Strand scission in DNA induced by dietary flavonoids: role of Cu(I) and oxygen free radicals and biological consequences of scission. Mol Cell Biochem. 1992 Apr; 111(1-2):3-9.
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• Reaction of furfural and methylfurfural with DNA: use of single-strand-specific nucleases. Food Chem Toxicol. 1991 Oct; 29(10):719-21.
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• Fazal F, Rahman A, Greensill J, Ainley K, Hadi SM, Parish JH. Strand scission in DNA by quercetin and Cu(II): identification of free radical intermediates and biological consequences of scission. Carcinogenesis. 1990 Nov; 11(11):2005-8.
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• Rahman A. Complexes involving quercetin, DNA and Cu(II). Carcinogenesis. 1990 Nov; 11(11):2001-3.
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• Specificity of the in vitro interaction of methylfurfural with DNA. Mutagenesis. 1990 Mar; 5(2):131-6.
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• Rahman A. Formation of strand breaks and interstrand cross-links in DNA by methylglyoxal. J Biochem Toxicol. 1990; 5(3):161-6.
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• Rahman A. Strand scission in DNA induced by quercetin and Cu(II): role of Cu(I) and oxygen free radicals. Carcinogenesis. 1989 Oct; 10(10):1833-9.
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• Hadi SM. Specificity of the interaction of furfural with DNA. Mutat Res. 1989 Mar; 225(3):101-6.
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