Abu-Bakr Al-Mehdi, M.D., Ph.D.

Abu-Bakr Al-Mehdi, Ph.D.

M.D.   Crimea Medical Institute, Simferopol Ukraine
Ph.D.   Crimea Medical Institute, Simferopol Ukraine
Post-doctoral   University of Pennsylvania
Current Position   Associate Professor
Phone   (251) 460-6704
E-mail   mehdi@southalabama.edu


Research Interests

Signal Compartmentalization by Source Translocation:  Mitochondria are motile organelles that exhibit perinuclear, periparasitic, and peripheral clustering with a variety of stimuli, such as hypoxia, viral and parasitic infections, oocyte maturation and fertilization.  We postulate that mitochondrial translocation is a response to increased demand for mitochondrial signaling molecules (reactive oxygen species, calcium) in a subcellular region. Currently, we are examining the effect of a variety of stimuli on mitochondrial translocation in endothelial and cancer cells and its dependence on microtubule based motor proteins, kinesin and dynein by multidimensional live-cell fluorescence microscopy.

Vasculogenesis in cancer metastasis. Growth and survival of solid primary and metastatic tumors with radii greater than oxygen-diffusion distance requires formation of blood vessels within tumors. The existing models of tumor vascularization of solid tumors involve sprouting or intussusceptive angiogenesis, co-option of existing vessels, or vasculogenic mimicry. Examining early metastatic lung tumors after tail-vein injection of a syngeneic breast cancer cell line in the nude mice, we have found the presence of endothelial cells in pre-hypoxia size tumors. This observation lays the foundation of a novel vasculogenic model where early incorporation of endothelial cells occurs before the onset of core hypoxia in metastatic lung tumors. We are working on the origins of these endothelial cells.

Publications:

1. Gillespie MN, Al-Mehdi A-, McMurtry IF. Mitochondria in hypoxic pulmonary vasoconstriction: Potential importance of compartmentalized reactive oxygen species signaling. American Journal of Respiratory and Critical Care Medicine. 2013;187(4):338-40.

2. Al-Mehdi A-, Pastukh VM, Swiger BM, Reed DJ, Patel MR, Bardwell GC, et al. Perinuclear mitochondrial clustering creates an oxidant-rich nuclear domain required for hypoxia-induced transcription. Science Signaling. 2012;5(231).

3. Parra-Bonilla G, Alvarez DF, Al-Mehdi A-, Alexeyev M, Stevens T. Critical role for lactate dehydrogenase A in aerobic glycolysis that sustains pulmonary microvascular endothelial cell proliferation. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2010;299(4):L513-22.

4. Wu S, Jian M-, Xu Y-, Zhou C, Al-Mehdi A-, Liedtke W, et al. Ca2+ entry via α1G and TRPV4 channels differentially regulates surface expression of P-selectin and barrier integrity in pulmonary capillary endothelium. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2009;297(4):L650-7.

5. Elzarrad K, Haroon A, Reed D, Al-Mehdi A-. Early incorporated endothelial cells as origin of metastatic tumor vasculogenesis. Clinical and Experimental Metastasis. 2009;26(6):589-98.

6. ElZarrad MK, Al-Mehdi AB. Connexin-43 facilitate metastatic tumor cell adhesion to lung vasculature. Microscopy and Microanalysis. 2008;14(SUPPL. 2):1512-3.

7. Elzarrad MK, Haroon A, Willecke K, Dobrowolski R, Gillespie MN, Al-Mehdi A-. Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium. BMC Medicine. 2008;6.

8. Jian M-, King JA, Al-Mehdi A-, Liedtke W, Townsley MI. High vascular pressure-induced lung injury requires P450 epoxygenase-dependent activation of TRPV4. American Journal of Respiratory Cell and Molecular Biology. 2008;38(4):386-92.

9. Breit JF, Ault-Ziel K, Al-Mehdi A-, Gillespie MN. Nuclear protein-induced bending and flexing of the hypoxic response element of the rat vascular endothelial growth factor promoter. FASEB Journal. 2008;22(1):19-29.

10. Hamanaka K, Jian M-, Weber DS, Alvarez DF, Townsley MI, Al-Mehdi AB, et al. TRPV4 initiates the acute calcium-dependent permeability increase during ventilator-induced lung injury in isolated mouse lungs. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2007;293(4):L923-32.

11. Haroon ATMY, Patel M, Al-Mehdi AB. Lung metastatic load limitation with hyperbaric oxygen. Undersea and Hyperbaric Medicine. 2007;34(2):83-90.

12. Al-Mehdi A-, Patel M, Haroon A, Reed D, Ohlsson-Wilhelm B, Muirhead K, et al. Increased depth of cellular imaging in the intact lung using far-red and near-infrared fluorescent probes. International Journal of Biomedical Imaging. 2006;2006.

13. Ruchko M, Gorodnya O, LeDoux SP, Alexeyev MF, Al-Mehdi A-, Gillespie MN. Mitochondrial DNA damage triggers mitochondrial dysfunction and apoptosis in oxidant-challenged lung endothelial cells. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2005;288(3 32-3):L530-5.

14. King JA, Ofori-Acquah SF, Stevens T, Al-Mehdi AB, Fodstad O, Jiang WG. Activated leukocyte cell adhesion molecule in breast cancer: Prognostic indicator. Breast cancer research : BCR. 2004;6(5):R478-487.

15. Kim J-, Wong CW, Goldsmith JD, Song C, Fu W, Allion M-, et al. Rapid apoptosis in the pulmonary vasculature distinguishes non-metastatic from metastatic melanoma cells. Cancer Lett. 2004;213(2):203-12.

16. Wei Z, Manevich Y, Al-Mehdi AB, Chattterjee S, Fisher AB. Ca2+ flux through voltage-gated channels with flow cessation in pulmonary microvascular endothelial cells. Microcirculation. 2004;11(6):517-26.

17. King J, Ofori-Acquah S, Stevens T, Al-Mehdi A-. Potential role for activated leukocyte cell adhesion molecule and neural cadherin in metastasis to the lung microcirculation. Chest. 2004;125(5 SUPPL.):150S-1S.

18. Wang H, Fu W, Im JH, Zhou Z, Santoro SA, Iyer V, et al. Tumor cell α3β1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis. J Cell Biol. 2004;164(6):935-41.

19. Chatterjee S, Al-Mehdi A-, Levitan I, Stevens T, Fisher AB. Shear stress increases expression of a KATP channel in rat and bovine pulmonary vascular endothelial cells. American Journal of Physiology - Cell Physiology. 2003;285(4 54-4):C959-67.

20. Roy A, Al-Mehdi AB, Mokashi A, Lahiri S. Importance of glomus cell plasma membrane and mitochondrial membrane potentials during acute hypoxia signaling in the rat carotid body [Internet]; 2003 [cited 2013 Oct 3]. Available from: www.scopus.com.

21. Fisher AB, Al-Mehdi AB, Wei Z, Song C, Manevich Y. Lung ischemia: Endothelial cell signaling by reactive oxygen species: A progress report [Internet]; 2003 [cited 2013 Oct 3]. Available from: www.scopus.com.

22. Matot I, Manevich Y, Al-Mehdi A-, Song C, Fisher AB. Fluorescence imaging of lipid peroxidation in isolated rat lungs during nonhypoxic lung ischemia. Free Radical Biology and Medicine. 2003;34(6):785-90.

23. Qiu H, Orr FW, Jensen D, Wang HH, McIntosh AR, Hasinoff BB, et al. Arrest of B16 melanoma cells in the mouse pulmonary microcirculation induces endothelial nitric oxide synthase-dependent nitric oxide release that is cytotoxic to the tumor cells. Am J Pathol. 2003;162(2):403-12.

24. Roy A, Li J, Al-Mehdi A-, Mokashi A, Lahiri S. Effect of acute hypoxia on glomus cell em and ψm as measured by fluorescence imaging. J Appl Physiol. 2002;93(6):1987-98.

25. Nassar T, Akkawi S, Bar-Shavit R, Haj-Yehia A, Bdeir K, Al-Mehdi A-, et al. Human α-defensin regulates smooth muscle cell contraction: A role for low-density lipoprotein receptor-related protein/α2-macroglobulin receptor. Blood. 2002;100(12):4026-32.

26. Wong CW, Song C, Grimes MM, Fu W, Dewhirst MW, Muschel RJ, et al. Intravascular location of breast cancer cells after spontaneous metastasis to the lung. Am J Pathol. 2002;161(3):749-53.

27. Song C, Al-Mehdi AB, Fischer AB. Erratum: An immediate endothelial cell signalling response to lung ischemia (american journal of physiology - lung cellular and molecular physiology (october 2001) 281 (L993-L1000)). American Journal of Physiology - Lung Cellular and Molecular Physiology. 2002;282(2 26-2):i-vi.

28. Song C, Al-Mehdi AB, Fisher AB. Erratum: An immediate endothelial cell signaling response to lung ischemia (american journal of physiology-lung cellular and molecular (october 2001) 281 (L993-L1000)). American Journal of Physiology - Lung Cellular and Molecular Physiology. 2002;282(6 26-6):ii-vi.

29. Fisher AB, Al-Mehdi AB, Manevich Y. Shear stress and endothelial cell activation. Crit Care Med. 2002;30(5 SUPPL.):S192-7.

30. Wei Z, Al-Mehdi AB, Fisher AB. Signaling pathway for nitric oxide generation with simulated ischemia in flow-adapted endothelial cells. American Journal of Physiology - Heart and Circulatory Physiology. 2001;281(5 50-5):H2226-32.

31. Song C, Al-Mehdi AB, Fisher AB. An immediate endothelial cell signaling response to lung ischemia. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2001;281(4 25-4):L993-L1000.

32. Manevich Y, Al-Mehdi A, Muzykantov V, Fisher AB. Oxidative burst and NO generation as initial response to ischemia in flow-adapted endothelial cells. American Journal of Physiology - Heart and Circulatory Physiology. 2001;280(5 49-5):H2126-35.

33. Wong CW, Lee A, Shientag L, Yu J, Dong Y, Kao G, et al. Apoptosis: An early event in metastatic inefficiency. Cancer Res. 2001;61(1):333-8.

34. Al-Mehdi AB, Song C, Tozawa K, Fisher AB. Ca2+ - and phosphatidylinositol 3-kinase-dependent nitric oxide generation in lung endothelial cells in situ with ischemia. J Biol Chem. 2000;275(51):39807-10.

35. Roy A, Rozanov C, Mokashi A, Daudu P, Al-mehdi AB, Shams H, et al. Mice lacking in gp91 phox subunit of NAD(P)H oxidase showed glomus cell [Ca2+](i) and respiratory responses to hypoxia. Brain Res. 2000;872(1-2):188-93.

36. Haj-Yehia A, Nassar T, Sachais BS, Kuo A, Bdeir K, Al-Mehdi AB, et al. Urokinase-derived peptides regulate vascular smooth muscle contraction in vitro and in vivo. FASEB Journal. 2000;14(10):1411-22.

37. Al-Mehdi AB, Zhao G, Tozawa K, Fisher AB. Depolarization-associated iron release with abrupt reduction in pulmonary endothelial shear stress in situ. Antioxidants and Redox Signaling. 2000;2(2):335-45.

38. Al-Mehdi AB, Tozawa K, Fisher AB, Shientag L, Lee A, Muschel RJ. Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: A new model for metastasis. Nat Med. 2000;6(1):100-2.

39. Fisher AB, Al-Mehdi A. Shear stress modulation of reactive oxygen species generation in lung ischemia. American Society of Mechanical Engineers, Bioengineering Division (Publication) BED. 1999;42:425-6.

40. Wei Z, Costa K, Al-Mehdi AB, Dodia C, Muzykantov V, Fisher AB. Simulated ischemia in flow-adapted endothelial cells leads to generation of reactive oxygen species and cell signaling. Circ Res. 1999;85(8):682-9.

41. Fisher AB, Al-Mehdi AB, Muzykantov V. Activation of endothelial NADPH oxidae as the source of a reactive oxygen species in lung ischemia. Chest. 1999;116(SUPPL.):25S-6S.

42. Tozawa K, Al-Mehdi AB, Muzykantov V, Fisher AB. In situ imaging of intracellular calcium with ischemia in lung subpleural microvascular endothelial cells. Antioxidants and Redox Signaling. 1999;1(2):145-54.

43. Al-Mehdi AB, Fisher AB. Invited editorial on 'tumor necrosis factor-α in ischemia and reperfusion injury in rat lungs'. J Appl Physiol. 1998;85(6):2003-4.

44. Al-Mehdi AB, Zhao G, Fisher AB. ATP-independent membrane depolarization with ischemia in the oxygen-ventilated isolated rat lung. American Journal of Respiratory Cell and Molecular Biology. 1998;18(5):653-61.

45. Al-Mehdi AB, Zhao G, Dodia C, Tozawa K, Costa K, Muzykantov V, et al. Endothelial NADPH oxidase as the source of oxidants in lungs exposed to ischemia or high K+. Circ Res. 1998;83(7):730-7.

46. Zhao G, Al-Mehdi AB, Fisher AB. Anoxia-reoxygenation versus ischemia in isolated rat lungs. American Journal of Physiology - Lung Cellular and Molecular Physiology. 1997;273(6 17-6):L1112-7.

47. Atochina EN, Muzykantov VR, Al-Mehdi AB, Danilov SM, Fisher AB. Normoxic lung ischemia/reperfusion accelerates shedding of angiotensin converting enzyme from the pulmonary endothelium. American Journal of Respiratory and Critical Care Medicine. 1997;156(4 PART I):1114-9.

48. Al-Mehdi AB, Shuman H, Fisher AB. Oxidant generation with K+-induced depolarization in the isolated perfused lung. Free Radical Biology and Medicine. 1997;23(1):47-56.

49. Al-Mehdi AB, Shuman H, Fisher AB. Intracellular generation of reactive oxygen species during nonhypoxic lung ischemia. American Journal of Physiology - Lung Cellular and Molecular Physiology. 1997;272(2 16-2):L294-300.

50. Al-Mehdi AB, Fisher AB. Detection of intracelluear superoxide generation with hydroethidine (he) during lung ischemia. FASEB Journal. 1996;10(3).

51. Ischiropoulos H, Nelson J, Duran D, Al-Mehdi A. Reactions of nitric oxide and peroxynitrite with organic molecules and ferrihorseradish peroxidase: Interference with the determination of hydrogen peroxide. Free Radical Biology and Medicine. 1996;20(3):373-81.

52. Al-Mehdi AB, Ischiropoulos H, Fisher AB. Endothelial cell oxidant generation during K+-induced membrane depolarization. J Cell Physiol. 1996;166(2):274-80.

53. Ischiropoulos H, Al-Mehdi AB. Peroxynitrite-mediated oxidative protein modifications. FEBS Lett. 1995;364(3):279-82.

54. Ischiropoulos H, Al-Mehdi AB, Fisher AB. Reactive species in ischemic rat lung injury: Contribution of peroxynitrite. American Journal of Physiology - Lung Cellular and Molecular Physiology. 1995;269(2 13-2):L158-64.

55. Fischer AB, Dodia C, Ayene I, Al-Mehdi A. Ischemia-reperfusion injury to the lung. Ann N Y Acad Sci. 1994;723:197-207.

56. Al-Mehdi A, Shuman H, Fisher AB. Fluorescence microtopography of oxidative stress in lung ischemia- reperfusion. Laboratory Investigation. 1994;70(4):579-87.

57. Al-Mehdi AB, Dodia C, Jain MK, Fisher AB. A phospholipase A2 inhibitor decreases generation of thiobarbituric acid reactive substance during lung ischemia-reperfusion. Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism. 1993;1167(1):56-62.

58. Ayene IS, Al-Mehdi AB, Fisher AB. Inhibition of lung tissue oxidation during ischemia/reperfusion by 2- mercaptopropionylglycine. Arch Biochem Biophys. 1993;303(2):307-12.

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