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Fabeha Fazal

TitleAssistant Professor
InstitutionSchool of Medicine and Dentistry
DepartmentPediatrics
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 850
Rochester NY 14642
 
 Overview
A major focus of research in my laboratory deals with understanding the role and regulation of actin-myosin interactions in endothelial cell (EC) inflammation, permeability, and apoptosis, especially in the settings of acute and chronic lung injury. We study pathways of EC inflammation, barrier dysfunction and apoptosis on the molecular, cellular, and animal level. We have uncovered novel and previously unrecognized role of actin cytoskeleton and non-muscle myosin light chain kinase (nmMLCK) in the regulation of cytoplasmic trafficking of NF-k? for its nuclear import to cause EC inflammation associate with intravascular coagulation and sepsis. More recently we have been involved in the identification of endoplasmic reticulum (ER) stress as an important determinant of EC inflammation and permeability associated with acute lung injury (ALI). In our most recent work, we have focused on understanding the role of nmMLCK in the pathogenesis of pulmonary emphysema caused by cigarette smoke (CS). The approaches ranging from biochemical, cellular, and molecular biology to in vivo gene delivery and lung physiology to study how pulmonary endothelium responds during acute and chronic lung inflammation/injury.

 
 Selected Publications
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  1. Leonard A, Marando C, Rahman A, Fazal F. Thrombin selectively engages LIM kinase 1 and slingshot-1L phosphatase to regulate NF-?B activation and endothelial cell inflammation. Am J Physiol Lung Cell Mol Physiol. 2013 Nov; 305(9):L651-64.
    View in: PubMed
  2. Fazal F, Bijli KM, Murrill M, Leonard A, Minhajuddin M, Anwar KN, Finkelstein JN, Watterson DM, Rahman A. Critical Role of Non-Muscle Myosin Light Chain Kinase in Thrombin-Induced Endothelial Cell Inflammation and Lung PMN Infiltration. PLoS One. 2013; 8(3):e59965.
    View in: PubMed
  3. 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.
    View in: PubMed
  4. Rahman A, Fazal F. Blocking NF-?B: an inflammatory issue. Proc Am Thorac Soc. 2011 Nov; 8(6):497-503.
    View in: PubMed
  5. 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.
    View in: PubMed
  6. 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.
    View in: PubMed
  7. 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.
    View in: PubMed
  8. 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.
    View in: PubMed
  9. 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.
    View in: PubMed
  10. 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.
    View in: PubMed
  11. 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.
    View in: PubMed
  12. Fazal F, Gu L, Ihnatovych I, Han Y, Hu W, Antic N, Carreira F, Blomquist JF, Hope TJ, Ucker DS, de Lanerolle P. Inhibiting myosin light chain kinase induces apoptosis in vitro and in vivo. Mol Cell Biol. 2005 Jul; 25(14):6259-66.
    View in: PubMed
  13. 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.
    View in: PubMed
  14. 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.
    View in: PubMed
  15. Nobe H, Nobe K, Fazal F, De Lanerolle P, Paul RJ. Rho kinase mediates serum-induced contraction in fibroblast fibers independent of myosin LC20 phosphorylation. Am J Physiol Cell Physiol. 2003 Mar; 284(3):C599-606.
    View in: PubMed
  16. Adami C, Pooley J, Glomb J, Stecker E, Fazal F, Fleming JO, Baker SC. Evolution of mouse hepatitis virus (MHV) during chronic infection: quasispecies nature of the persisting MHV RNA. Virology. 1995 Jun 1; 209(2):337-46.
    View in: PubMed
  17. Fleming JO, Adami C, Pooley J, Glomb J, Stecker E, Fazal F, Baker SC. Mutations associated with viral sequences isolated from mice persistently infected with MHV-JHM. Adv Exp Med Biol. 1995; 380:591-5.
    View in: PubMed
  18. 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.
    View in: PubMed
  19. 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.
    View in: PubMed
  20. 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.
    View in: PubMed

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