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Victor E. Laubach, PhD |
Research Interests:
1. Mechanisms of lung regeneration (Compensatory Lung Growth)
2. Growth and function of transplanted lungs
3. Lung ischemia/reperfusion injury, endothelial dysfunction, and inflammation
4. Angiogenesis in compensatory lung growth
5. Role of nitric oxide in compensatory lung growth and ischemia/reperfusion injury
Techniques in Use:
1. Pneumonectomy surgery in rats and mice
2. In vivo lung ischemia/reperfusion models in rats and mice
3. Isolated buffer-perfused lung ischemia/reperfusion model in mice
4. Lung transplantation in pigs and rats
5. Magnetic resonance imaging (MRI) of mouse/rat lung
6. Molecular and cell biology techniques used in the lab including: Northern blot, Southern blot, Western blot, polymerase chain reaction (PCR), electrophoretic gel mobility shift assay (EMSA), ribonuclease protection assay (RPA), knockout/transgenic mice, purification of primary mouse lung endothelial and epithelial cells, cell culture, immunohistochemistry, enzyme-linked immunosorbant assay (ELISA), flow cytometry, nitric oxide assays, recombinant DNA and cloning, lung morphometry, protein array and gene array.
Current Summary:
Pneumonectomy (removal of one lung) results in rapid compensatory growth of the remaining lung. The mechanisms that regulate this growth are unknown, and the long-term goal of my research is to understand the molecular mediators that trigger and regulate compensatory lung growth. We are studying the growth of these lungs in various ways. Morphometric techniques are used to measure percent respiratory tissue and alveolar size and density. Immunohistochemistry for bromo-deoxyuridine is used to measure cell proliferation index. The expression of growth factors and growth factor receptors (EGF, HGF, KGF, FGF, PDGF) are being measured by several techniques including Western analysis, ELISA, RT-PCR, gene array and protein array. We have demonstrated that exogenous administration of epidermal growth factor, keratinocyte growth factor or retinoic acid can further induce compensatory lung growth. We are currently studying the role of nitric oxide on compensatory lung growth. We have demonstrated that compensatory lung growth is impaired in eNOS- and iNOS-knockout mice, and we have shown that epidermal growth factor receptor and vascular endothelial growth factor (VEGF) are upregulated during compensatory lung growth. Our studies are directed at testing the overall hypothesis that nitric oxide is a key mediator of compensatory lung growth through the modulation of angiogenesis and type II alveolar cell proliferation.
A second area of research is the study of lung ischemia-reperfusion injury. We are investigating the critical role of NF-kappaB in acute inflammation of the lung. We have demonstrated the rapid nuclear activation of NF-kappaB following lung transplantation and have shown that inhibition of NF-kappaB activation improves lung function and diminishes inflammation. In an ex vivo model of isolated blood-perfused rabbit lungs, we are studing NF-kB and the role leukocytes and macrophages in reperfusion injury. We now have established both mouse and rat in situ models of warm lung ischemia-reperfusion, and we are utilizing mouse knockout strains to look at the role of various genes in lung reperfusion injury.
Selected Publications:
Li D, Fernandez LG, Dodd OJ, Langer J, Wang D, and Laubach VE. Upregulation of hypoxia-induced mitogenic factor in compensatory lung growth after pneumonectomy. Am J Respir Cell Mol Biol (In Press ) 2005.
Le Cras TD, Fernandez LG, Pastura PA, and Laubach VE. Vascular growth and remodeling in compensatory lung growth following right lobectomy. J Appl Physiol (In Press) 2005.
Maxey T, Enelow R, Gaston B, and Kron I, Laubach VE, and Doctor A. Tumor necrosis factor-alpha from resident alveolar macrophages in a key initiating factor in pulmonary ischemia reperfusion injury. J. Thorac. Cardiovasc. Surg. 127(2):541-547, 2004.
American Thoracic Society Workshop Report: Mechanisms and Limits of Induced Postnatal Lung Growth. Am. J. Respir. Crit. Care Med. 170:319-343, 2004.
Kaza AK, Kron IL, Leuwerke S, Fiser SM, Long SM, Phillips AN, Jern JA, Tribble CG, Laubach VE. Keratinocyte growth factor enhances post-pneumonectomy lung growth by alveolar cell proliferation. Circulation 106(suppl 1): I120-I124, 2002.
Kaza AK, Cope JT, Long SM, Fiser SM, Kern JA, Tribble CG, Kron IL, and Laubach VE. Contrasting nature of lung growth following transplantation and lobectomy. J. Thorac. Cardiovasc. Surg. 123(2):288-294, 2002.
Kaza AK, Kron IL, Long SM, Fiser SM, Stevens PM, Kern JA, Tribble CG, and Laubach VE. Epidermal growth factor receptor up-regulation is associated with lung growth after lobectomy. Ann. Thorac. Surg. 72(2):380-385, 2001.
Fiser SM, Tribble CG, Long SM, Kaza, AK, Cope JT, Laubach VE, Kern JA, and Kron IL. Lung transplant reperfusion injury involves pulmonary macrophages and circulating leukocytes in a biphasic response. J. Thorac. Cardiovasc. Surg. 121(6):1069-1075, 2001.
Kaza, AK, Kron IL, Kern JA, Fiser SM, Long SM, Nguyen RP, Shockey KS, Tribble CG, and Laubach VE. Retinoic acid enhances lung growth after penumonectoy. Ann. Thorac. Surg. 71:1645-50, 2001.
Kaza, AK, Laubach VE, Kern JA, Long SM, Fiser SM, Tepper JA, Nguyen RP, Shockey KS, Tribble CG, Kron IL. Epidermal growth factor augments post-pneumonectomy lung growth. J. Thorac. Cardiovasc. Surg. 120:916-922, 2000.
Ross SD, Kron IL, Gangemi JJ, Shockey KS, Kern JA, Tribble CG,and Laubach VE. Attenuation of lung reperfusion injury after transplantation using an inhibitor of nuclear factor-kB. Am. J. Physiol. (Lung Cell. Mol. Physiol.) 279(3):L528-L536, 2000.
Laubach VE, Foley PL, Shockey KS, Tribble CG, and Kron IL. Protective roles of nitric oxide and testosterone in endotoxemia: evidence from NOS2-deficient mice. Am. J. Physiol. 275 (Heart Circ. Physiol. 44):H2211-H2218, 1998.
Laubach, VE, Shesely EG, Smithies O, and Sherman PA. Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death. Pro. Natl. Acad. Sci. USA. 92(23):10688-10692, 1995.
Links to learn more about Dr. Laubach's research:
http://www.healthsystem.virginia.edu/internet/tcv-lab/
http://myprofile.cos.com/vel8n
http://www.ctsnet.org/doc/4991
http://www.healthsystem.virginia.edu/internet/researchfaculty/detail.cfm?people_id=vel8n