University of Michigan, 1981 3008 Wahl Hall East
3901 Rainbow Boulevard
Kansas City, KS 66160
Phone: (913) 588-7478
Fax: (913) 588-7430
jwood2@kumc.edu
Systemic hypoxia occurs at high altitude and in a variety of cardio-pulmonary diseases. Few studies have examined its effects on the microcirculation despite considerable clinical evidence suggestive of microvascular inflammation during hypoxia (i.e., high altitude cerebral edema). In fact, it is generally accepted that microvascular injury occurs during elevated tissue oxygen levels (during reperfusion of organs after prolonged ischemia) rather than during low tissue oxygen levels during ischemia. Currently, our major goal is to examine mechanisms responsible for microvascular inflammation during acute systemic hypoxia as well as the mechanisms involved in adaptation to chronic hypoxia. These studies are in collaboration with Dr. Norberto Gonzalez.
MD/PhD Candidate Graduate Students
Al Casillan
Al is beginning his fourth-year as a MD/PhD student at the University of Kansas School of Medicine and is a member of Dr. John Wood's lab. Al earned his bachelor's degree in chemical engineering from the University of Kansas in Lawrence. Past studies from our lab have demonstrated that acute hypoxia stimulates leukocyte-endothelial adhesive interactions. Following chronic exposure to hypoxia, however, this response is not seen. Following chronic hypoxia the microcirculation becomes "acclimatized," and the deleterious effects of hypoxia on the microcirculation are no longer observed. Using intravital microscopy and the rat mesenteric microcirculation as a model, Al is trying to delineate the mechanisms that are responsible for microvascular acclimatization to systemic hypoxia. His first paper asked basic questions about the role of platelet activating factor (PAF) in the microcirculatory response to systemic hypoxia, and he showed that PAF is an important component in the chain of events leading to hypoxia-induced leukocyte-endothelial interactions. His current work is examining the role of nitric oxide and nitric oxide synthases in the microvascular acclimatization process. Once finishing his PhD thesis, Al will start back in medical school and complete his clinical rotations.
Joe McDonald
Joe is in his fourth year and working on an MD/PhD at the University of Kansas School of Medicine. He obtained a masters degree at KU in Lawrence in microbiology /immunology, with research focusing on B cell activation, chemokines, and transplant rejection. He then spent the year prior to medical school as well as the first year while taking classes in medical school working with Doug Wright, PhD at KUMC on neurotrophins and nerve injury repair. Joe then moved to a project with Lisa Felzien, PhD working on the role of inflammatory mediators in the aging brain. Towards the end of his second year, he began working in Dr. Wood's lab which focuses on microvascular responses to systemic hypoxia. High altitude cerebral edema (HACE) is a serious clinical syndrome believed to be caused, in part, by the systemic hypoxia that results when entering increased elevations. The effects of systemic hypoxia on the cerebral microcirculation are largely unstudied, so Joe's work is starting out by addressing basic questions about the microcirculatory response to systemic hypoxia in the brain. He is submitting a manuscript for publication which shows that systemic hypoxia promotes leukocyte-endothelial adherence in pial venules of the cerebral cortex. The mechanism of this response appears to involve reactive oxygen species (ROS) generation and depletion of nitric oxide (a potent anti-inflammatory agent) within the cerebral microcirculation. His thesis will eventually lead to an exploration of the inflammatory mediators involved in the response and a further characterization of the cascade of events following systemic hypoxia.
Publications during last 3 years
Forster J, P Beebee, H Wang, and JG Wood. Effect of L-NAME on systemic blood pressure differs between rat strains. J Surg Res 96:218-223, 2001.
Steiner DRS, Gonzalez NC, and JG Wood. Leukotriene B4 promotes reactive oxidant generation and leukocyte adherence during acute hypoxia. J Appl Physiol 91:1160-1167, 2001.
Gonzalez NC and JG Wood. Leukocyte-endothelial interactions in environmental hypoxia. Adv Exp Med Biol 502:39-60, 2001.
Steiner DRS, NC Gonzalez, and JG Wood. Interaction between reactive oxygen species and nitric oxide in the microvascular response to systemic hypoxia. J Appl Physiol 93:1411-1418, 2002.
Childs EW, KF Udobi , JG Wood, FA Hunter, DM Smalley, and LY Cheung. In vivo visualization of reactive oxidants and leukocyte-endothelial adherence following hemorrhagic shock. Shock 18:423-7, 2002.
Steiner DRS, NC Gonzalez, and JG Wood. Mast cells mediate the microvascular inflammatory response to systemic hypoxia. J Appl Physiol 94:325-334, 2003.
Gonzalez NC, Steiner DRS, and Wood JG. Dexamethasone prevents the microcirculatory inflammatory response to systemic hypoxia. Health and Height. Proc 5th World Congress on Mountain Med High Altitude Physiology, pp. 31-38, 2003.
Casillan AJ, Gonzalez NC, Johnson JS, Steiner DRS, and Wood JG. Mesenteric microvascular inflammatory responses to systemic hypoxia are mediated by PAF and LTB4. J Appl Physiol 94:2313-2322, 2003.
Shah S, Allen J, Wood JG, and Gonzalez NC. Dissociation between skeletal muscle microvascular PO2 and hypoxia-induced microvascular inflammation. J Appl Physiol 94:2323-2339, 2003.
Dix R, Orth T, Allen J, Wood JG, and Gonzalez NC. Activation of mast cells by systemic hypoxia, but not by local hypoxia, mediates increased leukocyte-endothelial adherence in cremaster venules. J Appl Physiol 95:2495-502, 2003.
Valenzeno DP, Wood JG, Gonzalez NC, and Tarr M. Photosensitization with emphasis on the cardiovascular system. In: CRC Handbook of Organic Photochemistry and Photobiology. Eds. W.M. Hospool and F. Lenci. CRC Press, Inc., Boca Raton, FL. 2003.
Schloerb PR, Wood JG, Casillan AJ, Tawfik O, and Udobi K. Bowel necrosis caused by water in jejunal feeding. JPEN J Parenter Enteral Nut 28:27-29, 2004.
Orth TA, Allen JA, Wood JG, and Gonzalez NC. Exercise training prevents the inflammatory response to hypoxia in cremaster venules. J Appl Physiol 98:2113-2118, 2005.
Orth TA, Allen JA, Wood JG, and Gonzalez NC. Plasma from conscious hypoxic rats stimulates leukocyte-endothelial interactions in normoxic cremaster venules. J Appl Physiol 99:290-297, 2005.
Orth TA, Allen JA, Wood JG, and Gonzalez NC. Plasma from conscious hypoxic rats stimulates leukocyte-endothelial interactions in normoxic cremaster venules. J Appl Physiol 99:290-297, 2005.
Ho-Chen JK, Ain R, Alt AR, Wood JG, and Gonzalez NC, and Soares MJ. Hypobaric hypoxia as a tool to study pregnancy-dependent responses at the maternal-fetal interface. Methods Mol Med 122:427-434, 2006.
Wood JG and Gonzalez NC. Reactive oxygen species and the microcirculation. Encyclopedia of the Microcirculation, D. Shepro, Editor. P. 805-809, 2006.
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The University of Kansas Medical Center