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Barbara Wegiel, Ph.D.

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Mentoring
Available: 08/11/17, Expires: 12/31/20

A major interest of our laboratory is a role of bile pigments and heme in inflammation, organ injury and cancer. We study heme oxygenase-1, an enzyme that generates carbon monoxide (CO), iron and biliverdin (BV). HO-1 acts in concert with biliverdin reductase (BVR) to form one of the strongest antioxidant, bilirubin (BR). We focus on the role of HO-1 and BVR in inflammation, liver injury and cancer biology. We have demonstrated that BVR acts as a signaling molecule and mediate anti-inflammatory effects of BV (PNAS, 2011; JBC, 2009). We continue to explore a role of BVR, HO-1 and bile pigments in a model of liver injury. Our hypothesis is that BVR is a major signaling molecule that is activated upon conversion of BV to BR and has potent regulatory effects in the innate immune system.

Student’s role: work with transgenic and knockout mice colony, in vitro cell culture and treatment, viral transduction and transfection of cells, learning and applying multiple biochemical and molecular biology assays.


Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01DK104714 (WEGIEL, BARBARA) Jan 1, 2016 - Dec 31, 2020
    NIH/NIDDK
    Role of biliverdin reductase during sterile inflammation in the liver.
    Role: Principal Investigator
  2. R21CA169904 (WEGIEL, BARBARA) Aug 6, 2013 - Jul 31, 2015
    NIH/NCI
    Heme degradation pathway and immunomodulation in prostate cancer.
    Role: Principal Investigator

Bibliographic
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.
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  1. Bisht K, Canesin G, Cheytan T, Li M, Nemeth Z, Csizmadia E, Woodruff TM, Stec DE, Bulmer AC, Otterbein LE, Wegiel B. Deletion of Biliverdin Reductase A in Myeloid Cells Promotes Chemokine Expression and Chemotaxis in Part via a Complement C5a--C5aR1 Pathway. J Immunol. 2019 May 15; 202(10):2982-2990. PMID: 30952817.
    Citations:    
  2. Daneshmandi S, Wegiel B, Seth P. Blockade of Lactate Dehydrogenase-A (LDH-A) Improves Efficacy of Anti-Programmed Cell Death-1 (PD-1) Therapy in Melanoma. Cancers (Basel). 2019 Mar 29; 11(4). PMID: 30934955.
    Citations:    
  3. Hedblom A, Hejazi SM, Canesin G, Choudhury R, Hanafy KA, Csizmadia E, Persson JL, Wegiel B. Heme detoxification by heme oxygenase-1 reinstates proliferative and immune balances upon genotoxic tissue injury. Cell Death Dis. 2019 Jan 25; 10(2):72. PMID: 30683864.
    Citations:    Fields:    
  4. Wegiel B, Vuerich M, Daneshmandi S, Seth P. Metabolic Switch in the Tumor Microenvironment Determines Immune Responses to Anti-cancer Therapy. Front Oncol. 2018; 8:284. PMID: 30151352.
    Citations:    
  5. Longhi MS, Vuerich M, Kalbasi A, Kenison JE, Yeste A, Csizmadia E, Vaughn B, Feldbrugge L, Mitsuhashi S, Wegiel B, Otterbein L, Moss A, Quintana FJ, Robson SC. Bilirubin suppresses Th17 immunity in colitis by upregulating CD39. JCI Insight. 2017 May 04; 2(9). PMID: 28469075.
    Citations: 2     Fields:    
  6. Seth P, Csizmadia E, Hedblom A, Vuerich M, Xie H, Li M, Longhi MS, Wegiel B. Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity. Cancer Res. 2017 07 01; 77(13):3632-3643. PMID: 28446465.
    Citations: 5     Fields:    Translation:HumansAnimalsCells
  7. Wang Y, Hedblom A, Koerner SK, Li M, Jernigan FE, Wegiel B, Sun L. Novel synthetic chalcones induce apoptosis in the A549 non-small cell lung cancer cells harboring a KRAS mutation. Bioorg Med Chem Lett. 2016 12 01; 26(23):5703-5706. PMID: 27810244.
    Citations: 1     Fields:    Translation:HumansCells
  8. Nemeth Z, Csizmadia E, Vikstrom L, Li M, Bisht K, Feizi A, Otterbein S, Zuckerbraun B, Costa DB, Pandolfi PP, Fillinger J, Döme B, Otterbein LE, Wegiel B. Alterations of tumor microenvironment by carbon monoxide impedes lung cancer growth. Oncotarget. 2016 Apr 26; 7(17):23919-32. PMID: 26993595.
    Citations: 7     Fields:    Translation:HumansAnimalsCells
  9. Wegiel B, Wang Y, Li M, Jernigan F, Sun L. Novel indolyl-chalcones target stathmin to induce cancer cell death. Cell Cycle. 2016 05 02; 15(9):1288-94. PMID: 26986925.
    Citations: 2     Fields:    Translation:HumansCells
  10. Wegiel B, Ahmed A. "Nucleosome debris" provokes coagulation and inflammation. Thromb Res. 2016 Jan; 137:1-2. PMID: 26603319.
    Citations:    Fields:    Translation:HumansAnimalsCells
  11. Nemeth Z, Li M, Csizmadia E, Döme B, Johansson M, Persson JL, Seth P, Otterbein L, Wegiel B. Heme oxygenase-1 in macrophages controls prostate cancer progression. Oncotarget. 2015 Oct 20; 6(32):33675-88. PMID: 26418896.
    Citations: 10     Fields:    Translation:HumansAnimalsCells
  12. Wegiel B, Hauser CJ, Otterbein LE. Heme as a danger molecule in pathogen recognition. Free Radic Biol Med. 2015 Dec; 89:651-61. PMID: 26456060.
    Citations: 16     Fields:    Translation:HumansAnimalsCells
  13. Eguchi T, Prince T, Wegiel B, Calderwood SK. Role and Regulation of Myeloid Zinc Finger Protein 1 in Cancer. J Cell Biochem. 2015 Oct; 116(10):2146-54. PMID: 25903835.
    Citations: 7     Fields:    Translation:HumansCells
  14. Ahmad S, Hewett PW, Fujisawa T, Sissaoui S, Cai M, Gueron G, Al-Ani B, Cudmore M, Ahmed SF, Wong MK, Wegiel B, Otterbein LE, Vítek L, Ramma W, Wang K, Ahmed A. Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation. Thromb Haemost. 2015 Feb; 113(2):329-37. PMID: 25354586.
    Citations: 7     Fields:    Translation:HumansAnimalsCells
  15. Wegiel B, Larsen R, Gallo D, Chin BY, Harris C, Mannam P, Kaczmarek E, Lee PJ, Zuckerbraun BS, Flavell R, Soares MP, Otterbein LE. Macrophages sense and kill bacteria through carbon monoxide-dependent inflammasome activation. J Clin Invest. 2014 Nov; 124(11):4926-40. PMID: 25295542.
    Citations: 42     Fields:    Translation:AnimalsCells
  16. Bisht K, Wegiel B, Tampe J, Neubauer O, Wagner KH, Otterbein LE, Bulmer AC. Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling. Biochem Biophys Res Commun. 2014 Jun 20; 449(1):94-9. PMID: 24814708.
    Citations: 6     Fields:    Translation:AnimalsCells
  17. Wegiel B, Hedblom A, Li M, Gallo D, Csizmadia E, Harris C, Nemeth Z, Zuckerbraun BS, Soares M, Persson JL, Otterbein LE. Heme oxygenase-1 derived carbon monoxide permits maturation of myeloid cells. Cell Death Dis. 2014 Mar 20; 5:e1139. PMID: 24651442.
    Citations: 13     Fields:    Translation:HumansAnimalsCells
  18. Wegiel B, Nemeth Z, Correa-Costa M, Bulmer AC, Otterbein LE. Heme oxygenase-1: a metabolic nike. Antioxid Redox Signal. 2014 Apr 10; 20(11):1709-22. PMID: 24180257.
    Citations: 30     Fields:    Translation:HumansAnimalsCells
  19. Li M, Gallo D, Csizmadia E, Otterbein LE, Wegiel B. Carbon monoxide induces chromatin remodelling to facilitate endothelial cell migration. Thromb Haemost. 2014 May 05; 111(5):951-9. PMID: 24477332.
    Citations: 1     Fields:    Translation:HumansAnimalsCells
  20. Wegiel B, Gallo D, Csizmadia E, Harris C, Belcher J, Vercellotti GM, Penacho N, Seth P, Sukhatme V, Ahmed A, Pandolfi PP, Helczynski L, Bjartell A, Persson JL, Otterbein LE. Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth. Cancer Res. 2013 Dec 01; 73(23):7009-21. PMID: 24121491.
    Citations: 36     Fields:    Translation:HumansAnimalsCells
  21. Wegiel B, Hanto DW, Otterbein LE. The social network of carbon monoxide in medicine. Trends Mol Med. 2013 Jan; 19(1):3-11. PMID: 23140858.
    Citations: 29     Fields:    Translation:Humans
  22. Banerjee P, Basu A, Wegiel B, Otterbein LE, Mizumura K, Gasser M, Waaga-Gasser AM, Choi AM, Pal S. Heme oxygenase-1 promotes survival of renal cancer cells through modulation of apoptosis- and autophagy-regulating molecules. J Biol Chem. 2012 Sep 14; 287(38):32113-23. PMID: 22843690.
    Citations: 23     Fields:    Translation:HumansCells
  23. Wegiel B, Otterbein LE. Go green: the anti-inflammatory effects of biliverdin reductase. Front Pharmacol. 2012; 3:47. PMID: 22438844.
    Citations: 23     
  24. Wegiel B, Gallo D, Csizmadia E, Roger T, Kaczmarek E, Harris C, Zuckerbraun BS, Otterbein LE. Biliverdin inhibits Toll-like receptor-4 (TLR4) expression through nitric oxide-dependent nuclear translocation of biliverdin reductase. Proc Natl Acad Sci U S A. 2011 Nov 15; 108(46):18849-54. PMID: 22042868.
    Citations: 24     Fields:    Translation:AnimalsCells
  25. Otterbein LE, Hedblom A, Harris C, Csizmadia E, Gallo D, Wegiel B. Heme oxygenase-1 and carbon monoxide modulate DNA repair through ataxia-telangiectasia mutated (ATM) protein. Proc Natl Acad Sci U S A. 2011 Aug 30; 108(35):14491-6. PMID: 21849621.
    Citations: 13     Fields:    Translation:AnimalsCells
  26. Hanto DW, Maki T, Yoon MH, Csizmadia E, Chin BY, Gallo D, Konduru B, Kuramitsu K, Smith NR, Berssenbrugge A, Attanasio C, Thomas M, Wegiel B, Otterbein LE. Intraoperative administration of inhaled carbon monoxide reduces delayed graft function in kidney allografts in Swine. Am J Transplant. 2010 Nov; 10(11):2421-30. PMID: 20977633.
    Citations: 17     Fields:    Translation:Animals
  27. Wegiel B, Persson JL. Effect of a novel botanical agent Drynol Cibotin on human osteoblast cells and implications for osteoporosis: promotion of cell growth, calcium uptake and collagen production. Phytother Res. 2010 Jun; 24 Suppl 2:S139-47. PMID: 19953582.
    Citations:    Fields:    Translation:HumansCells
  28. Wegiel B, Evans S, Hellsten R, Otterbein LE, Bjartell A, Persson JL. Molecular pathways in the progression of hormone-independent and metastatic prostate cancer. Curr Cancer Drug Targets. 2010 Jun; 10(4):392-401. PMID: 20384583.
    Citations: 14     Fields:    Translation:HumansCells
  29. Wegiel B, Gallo DJ, Raman KG, Karlsson JM, Ozanich B, Chin BY, Tzeng E, Ahmad S, Ahmed A, Baty CJ, Otterbein LE. Nitric oxide-dependent bone marrow progenitor mobilization by carbon monoxide enhances endothelial repair after vascular injury. Circulation. 2010 Feb 02; 121(4):537-48. PMID: 20083679.
    Citations: 26     Fields:    Translation:AnimalsCells
  30. Wegiel B, Jiborn T, Abrahamson M, Helczynski L, Otterbein L, Persson JL, Bjartell A. Cystatin C is downregulated in prostate cancer and modulates invasion of prostate cancer cells via MAPK/Erk and androgen receptor pathways. PLoS One. 2009 Nov 23; 4(11):e7953. PMID: 19956729.
    Citations: 25     Fields:    Translation:HumansCells
  31. Bil J, Wlodarski P, Winiarska M, Kurzaj Z, Issat T, Jozkowicz A, Wegiel B, Dulak J, Golab J. Photodynamic therapy-driven induction of suicide cytosine deaminase gene. Cancer Lett. 2010 Apr 28; 290(2):216-22. PMID: 19822393.
    Citations:    Fields:    Translation:AnimalsCells
  32. Wegiel B, Baty CJ, Gallo D, Csizmadia E, Scott JR, Akhavan A, Chin BY, Kaczmarek E, Alam J, Bach FH, Zuckerbraun BS, Otterbein LE. Cell surface biliverdin reductase mediates biliverdin-induced anti-inflammatory effects via phosphatidylinositol 3-kinase and Akt. J Biol Chem. 2009 Aug 07; 284(32):21369-78. PMID: 19509285.
    Citations: 40     Fields:    Translation:HumansAnimalsCells
  33. da Silva CG, Specht A, Wegiel B, Ferran C, Kaczmarek E. Mechanism of purinergic activation of endothelial nitric oxide synthase in endothelial cells. Circulation. 2009 Feb 17; 119(6):871-9. PMID: 19188511.
    Citations: 30     Fields:    Translation:HumansCells
  34. Wegiel B, Ekberg J, Talasila KM, Jalili S, Persson JL. The role of VEGF and a functional link between VEGF and p27Kip1 in acute myeloid leukemia. Leukemia. 2009 Feb; 23(2):251-61. PMID: 18987662.
    Citations: 7     Fields:    Translation:HumansCells
  35. Wegiel B, Bjartell A, Tuomela J, Dizeyi N, Tinzl M, Helczynski L, Nilsson E, Otterbein LE, Härkönen P, Persson JL. Multiple cellular mechanisms related to cyclin A1 in prostate cancer invasion and metastasis. J Natl Cancer Inst. 2008 Jul 16; 100(14):1022-36. PMID: 18612129.
    Citations: 29     Fields:    Translation:HumansAnimalsCells
  36. Wegiel B, Bjartell A, Culig Z, Persson JL. Interleukin-6 activates PI3K/Akt pathway and regulates cyclin A1 to promote prostate cancer cell survival. Int J Cancer. 2008 Apr 01; 122(7):1521-9. PMID: 18027847.
    Citations: 53     Fields:    Translation:HumansCells
  37. Wegiel B, Chin BY, Otterbein LE. Inhale to survive, cycle or die? Carbon monoxide and cellular proliferation. Cell Cycle. 2008 May 15; 7(10):1379-84. PMID: 18418071.
    Citations: 3     Fields:    Translation:HumansCells
  38. Ollinger R, Wang H, Yamashita K, Wegiel B, Thomas M, Margreiter R, Bach FH. Therapeutic applications of bilirubin and biliverdin in transplantation. Antioxid Redox Signal. 2007 Dec; 9(12):2175-85. PMID: 17919067.
    Citations: 33     Fields:    Translation:HumansAnimalsCells
  39. Bilban M, Haschemi A, Wegiel B, Chin BY, Wagner O, Otterbein LE. Heme oxygenase and carbon monoxide initiate homeostatic signaling. J Mol Med (Berl). 2008 Mar; 86(3):267-79. PMID: 18034222.
    Citations: 70     Fields:    Translation:HumansAnimalsCells
  40. Haschemi A, Wagner O, Marculescu R, Wegiel B, Robson SC, Gagliani N, Gallo D, Chen JF, Bach FH, Otterbein LE. Cross-regulation of carbon monoxide and the adenosine A2a receptor in macrophages. J Immunol. 2007 May 01; 178(9):5921-9. PMID: 17442976.
    Citations: 17     Fields:    Translation:AnimalsCells
  41. Chin BY, Jiang G, Wegiel B, Wang HJ, Macdonald T, Zhang XC, Gallo D, Cszimadia E, Bach FH, Lee PJ, Otterbein LE. Hypoxia-inducible factor 1alpha stabilization by carbon monoxide results in cytoprotective preconditioning. Proc Natl Acad Sci U S A. 2007 Mar 20; 104(12):5109-14. PMID: 17360382.
    Citations: 69     Fields:    Translation:HumansAnimalsCells
  42. Zuckerbraun BS, Chin BY, Wegiel B, Billiar TR, Czsimadia E, Rao J, Shimoda L, Ifedigbo E, Kanno S, Otterbein LE. Carbon monoxide reverses established pulmonary hypertension. J Exp Med. 2006 Sep 04; 203(9):2109-19. PMID: 16908624.
    Citations: 36     Fields:    Translation:HumansAnimalsCells
  43. Dulak J, Zagorska A, Wegiel B, Loboda A, Jozkowicz A. New strategies for cardiovascular gene therapy: regulatable pre-emptive expression of pro-angiogenic and antioxidant genes. Cell Biochem Biophys. 2006; 44(1):31-42. PMID: 16456232.
    Citations: 5     Fields:    Translation:HumansAnimals
  44. Loboda A, Jazwa A, Wegiel B, Jozkowicz A, Dulak J. Heme oxygenase-1-dependent and -independent regulation of angiogenic genes expression: effect of cobalt protoporphyrin and cobalt chloride on VEGF and IL-8 synthesis in human microvascular endothelial cells. Cell Mol Biol (Noisy-le-grand). 2005 Sep 30; 51(4):347-55. PMID: 16309584.
    Citations: 24     Fields:    Translation:HumansCells
  45. Wegiel B, Bjartell A, Ekberg J, Gadaleanu V, Brunhoff C, Persson JL. A role for cyclin A1 in mediating the autocrine expression of vascular endothelial growth factor in prostate cancer. Oncogene. 2005 Sep 22; 24(42):6385-93. PMID: 16007189.
    Citations: 12     Fields:    Translation:HumansCells
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.