Natalie R. Bauer, Ph.D.
USA Department of Pharmacology
Ph.D.: University of South Alabama
Post-doctoral: Mitchell Cancer Institute, University of South Alabama, 2003-2006; Cardiovascular and Pulmonary Research, University of Colorado Health Sciences Center, 2001-2003
Phone: (251) 461-1567
There is an emerging field of study relating to cell-cell communication by small vesicles of cell membrane called microparticles (MPs). MPs are 0.2-1 µm in diameter and are released when cells are either stimulated or beginning to die (i.e. undergoing apoptosis). MPs carry, on their membrane, markers from the parent cells from which they are derived. MPs also carry signaling molecules inside the vesicle such as transcription factors and mRNA which can be transferred to and used by other cells. The focus of my laboratory is to determine how MPs are released and what their signaling mechanisms and effects are in the pulmonary vasculature.
It is currently well established that MP numbers increase in diseases such as metabolic syndrome and cardiovascular disease. What remains unknown is the direct role of MPs in pulmonary diseases. Recently, our lab determined that the microvascular endothelium of the pulmonary capillaries release MPs when stimulated by low oxygen tension, hypoxia. The pulmonary microvascular endothelial bed is the area where most gas exchange in the lung takes place due to proximity to the alveoli and surface area exposure. It is also the area of the lung most affected by ventilation-perfusion matching and ischemia-reperfusion injury in the setting of transplant or sickle cell disease. All of these cases have a common component of hypoxic insult to the microvasculature, which could contribute to release of MPs.
Two avenues of investigation are opened by the finding that hypoxia induces microparticle release: 1) What is on the membrane or carried inside of these MPs that may induce downstream signaling cascades? 2) What downstream vascular beds do these MPs target and what signaling cascades do they stimulate in the recipient cells? We have begun studies into the functional roles the released MPs play in signaling to downstream vascular beds. We have found that MPs released during hypoxia stimulate pulmonary microvascular endothelial monolayers to become permeable. In the whole lung setting this would translate to the development of pulmonary edema and prevent proper oxygenation of the blood. We further plan to determine the role of MPs in whole lung physiology and other forms of pathophysiology, such as pulmonary hypertension.
Overall, the goals of my lab are to establish the basic principles of MP regulated cell signaling in the pulmonary vasculature. Understanding of the role of MPs in pulmonary vasculature reactivity and permeability may have direct clinical applications as well as provide new pharmacologic targets in the prevention or treatment of lung diseases.
- Hargett LA, Scruggs AB, Toba M, Alzoubi A, McMurtry IF, Bauer NN. “Early exercise intervention prevents progression of severe pulmonary arterial hypertension in the sugen/hypoxia/normoxia rat model.” Am J Respir Crit Care Med 187 (2013): A4640.
- O’Neill KD, Reece A, Alzoubi A, Toba M, Oka M, Bauer NN, McMurtry IF, Fagan KA. “The aberrant morphogenesis of Alpha 5 and Beta 1 integrins in an animal model of severe pulmonary arterial hypertension.” Am J Respir Crit Care Med 187 (2013): A1757.
- Hargett LA, Bauer NN. “On the origin of microparticles: from ‘platelet dust’ to mediators of intercellular communication.” Pulm Circ 3(2) (2013): 329-40.
- Hargett LA, McLendon J, Gerthoffer W, Bauer NN. “Microparticles from PAH animals increase adhesion molecule expression in the pulmonary microcirculation.” FASEB J 27 (2013): 707.4.
- Gairhe S, Bauer NN, Gebb SA, McMurtry IF. “Serotonin passes through myoendothelial gap junctions to promote pulmonary arterial smooth muscle cell differentiation.” American Journal of Physiology - Lung Cellular and Molecular Physiology 303(9) (2012): L767-77.
- Alzoubi A, Toba M, Abe K, Bauer NN, Fagan K, McMurtry IF, Oka M. “Dehydroepiandrosterone restores right ventricular structure and function in a pre-clinical model of severe pulmonary arterial hypertension.” Am J Respir Crit Care Med 185 (2012): A3449.
- Hargett LA, Brown L, Sayner S, Bauer NN. “Microparticles from pulmonary microvascular endothelial cells contain cyclic AMP.” Am J Resp Crit Care Med 185 (2012): A4819.
- Gairhe S, Bauer NN, Gebb SA, McMurtry IF. “Myoendothelial gap junctional signaling induces differentiation of pulmonary arterial smooth muscle cells.” American Journal of Physiology - Lung Cellular and Molecular Physiology 301(4) (2011): L527-35.
- Alzoubi A, Toba M, Abe K, Bauer N, Fagan KA, McMurtry I, Oka M. “Dehydroepiandrosterone inhibits the infiltration of proliferative bone marrow-derived hematopoietic stem cells into the perivascular space of remodeled pulmonary arteries of SU5416/hypoxia/normoxia-exposed rats.” The Proceedings of the American Thoracic Society International Conference (2011); Denver, CO. p. 255. Abstract no. A3422.
- Bauer N, Quinn B, Toba M, Abe KA, Alzoubi A, Oka M, McMurtry IF. “Circulating microparticles as biomarkers of disease progression in a preclinical model of pulmonary arterial hypertension.” The Proceedings of the American Thoracic Society International Conference (2011); Denver, CO. p. 351. Abstract no. A4960.
- Bauer N, Quinn B. Toba M, Alzoubi A, Abe K, Oka M, McMurtry IF. “Leukocyte and endothelial microparticle phenotypes are increased across the pulmonary vascular bed in a preclinical model of severe pulmonary arterial hypertension.” The Proceedings of the American Thoracic Society International Conference (2011); Denver, CO. p. 351. Abstract no. A4961.
- Toba M, Alzoubi A, Abe K, Urakami T, Komatsu M, Jarvinen T, Mann D, Ruoslahti E, Bauer NR, Fagan KA, McMurtry IF, Oka M. “The homing peptide CAR markedly enhances the pulmonary vasodilator efficacy and selectivity of the Rho kinase inhibitor fasudil.” Circulation 122 (2010): Abstract no: A13022.
- Erzurum S, Rounds SI, Stevens T, Aldred M, Aliotta J, Archer SL, et al. “Strategic plan for lung vascular research: An NHLBI-ORDR workshop report.” American Journal of Respiratory and Critical Care Medicine 182(12) (2010): 1554-62.
- Bauer N, Rai J, Chen H, Harris L, Shevde L, King J. “Breast cancer microparticles promote formation of a microenvironment favorable for lung metastasis.” FASEB J 24 (2010): 592.6.
- Bauer N, Smith CA. “Inhibition of T-type calcium channels in pulmonary microvascular endothelium causes increased release of hypoxia-induced microparticles.” Am J Respir Crit Care Med 181 (2010): A3433.
- Bauer N, Smith CA. “Pulmonary microvascular endothelial microparticle release is governed by Rho kinase signaling and T-type calcium channel activation.” Am J Respir Crit Care Med 181 (2010): A3439.
- Bauer NN, Baker TJ, Rai J, Moore TM. “Soluble CD40L directly regulates PMVEC Barrier function.” Am J Respir Crit Care Med 179 (2009): A2327.
- Gairhe S, Bauer N, Gerthoffer W, McMurtry IF. “Effect of co-culture with pulmonary arterial endothelial cells on phenotype of pulmonary arterial smooth muscle cells.” FASEB J (2009): 769.3
- Rai J, King JA, Moore TM, Bauer NN. “Soluble CD40 ligand stimulates functional microparticle release from pulmonary microvascular endothelium.” FASEB J 23 (2009): 1024.8.
- Bauer N, Rai J, Chen H, Harris L, Shevde L, Moore T, King J. “Microparticles/exomes isolation and TEM analysis.” Microscopy Today 17(2) (2009): 42-5.
- King J, Syklawer E, Chen H, Resmondo J, McDonald F, Stevens T, Shevde L, Ofori-Acquah S, Moore T, Bauer N. “Lung endothelial cells express ALCAM on released exosomes/microparticles.” Microscopy and Microanalysis 14(SUPPL. 2) (2008): 1520-1.
- King J, Agarwal S, Syklawer E, Prasain N, Chen H, Resmondo J, McDonald F, Bauer N, Alvarez D, Wu S, Stevens T, Shevde L, Moore T, Townsley M. “Quantum dots - utilization in TEM.” Microscopy and Microanalysis 14(SUPPL. 2) (2008): 702-3.
- Bauer NN, Moore TM, Kapadia PD, Townsley MI, McMurtry IF. “Hypoxia-induced pulmonary endothelial microparticle generation regulations pulmonary microvascular endothelial cell permeability.” FASEB J (2008) Abstract no: 1178.7.
- Bauer NN, Chen Y-, Samant RS, Shevde LA, Fodstad O. “Rac1 activity regulates proliferation of aggressive metastatic melanoma.” Exp Cell Res 313(18) (2007): 3832-9.
- Bauer NR, Moore TM, McMurtry IF. “Rodent models of PAH: Are we there yet?” American Journal of Physiology - Lung Cellular and Molecular Physiology 293(3) (2007): L580-2.
- Garat CV, Fankell D, Erickson PF, Reusch JE-, Bauer NN, McMurtry IF, et al. “Platelet-derived growth factor BB induces nuclear export and proteasomal degradation of CREB via phosphatidylinositol 3-kinase/Akt signaling in pulmonary artery smooth muscle cells.” Mol Cell Biol 26(13) (2006): 4934-48.
- Sisbarro L, Ihida-Stambunj K, Stevens T, Bauer N, McMurtry I, Jones PL. “The extracellular matrix microenvironment specifies pulmonary endothelial cell identity: Roles of tenascin-G and RhoA.” Chest. 128(6 SUPPL.) (2005)
- Nagaoka T, Morio Y, Casanova N, Bauer N, Gebb S, McMurtry I, et al. “Rho/Rho kinase signaling mediates increased basal pulmonary vascular tone in chronically hypoxic rats.” American Journal of Physiology - Lung Cellular and Molecular Physiology 287(4 31-4) (2004): L665-72.
- Fagan KA, Oka M, Bauer NR, Gebb SA, Ivy DD, Morris KG, et al. “Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of rho-kinase.” American Journal of Physiology - Lung Cellular and Molecular Physiology 287(4 31-4) (2004): L656-64.
- McMurtry IF, Bauer NR, Fagan KA, Nagaoka T, Gebb SA, Oka M. “Hypoxia and Rho/Rho-kinase signaling: Lung development versus hypoxic pulmonary hypertension” [Internet]; (2003). Available from: www.scopus.com.
- Bauer NN, Stevens T, Gebb SA, McMurtry IF. “Hypoxia stimulates Rho A/Rho kinase signaling and stress fiber formation in pulmonary microvascular, but not macrovascular endothelial cells.” FASEB J 17(4 pt. 1)Suppl S (2003): A411.
- Bauer NN, Stevens T. “Putative role for a myosin motor in store-operated calcium entry.” Cell Biochem Biophys 37(1) (2002): 53-70.
- Norwood N, Cioffi D, Wu S, Dudek S, Garcia JGN, Stevens T. “Calcium Store Depletion Promotes Tyrosine Phosphorylation of Myosin Light Chain Kinase.” FASEB J (2002).
- Norwood N, Wu S, Dudek S, Garcia JGN, Stevens T. “Endothelial Cell Myosin Light Chain Kinase-1 and Activation of Store Operated Calcium Entry.” FASEB J 15 (2001): A492.
- El-Menshawi M, Moore TM, Norwood N, Stevens T. “Transcytosis Through Lung Endothelium: Implications for Inflammation.” FASEB J 14 (2000): A129.
- Norwood N, Moore T, Stevens T. “Use of Myosin Light Chain Kinase Inhibitor, ML-9, Reveals a Mechanism for Increased Pulmonary Artery Endothelial Permeability.” FASEB J 14 (2000): A693.
- Norwood N, Cioffi D, Moore T and Stevens T. “Distinct Regulation of Endothelial Cell Permeability by Proteolytic and Direct Activation of the Thrombin Receptor.” FASEB J 14 (2000): A694.
- Norwood N, Moore T, Creighton J, Babal P, Bhattacharjee R, Stevens T. “Myosin Light Chain Kinase Regulates Activation of Store-Operated Calcium Entry in Pulmonary Artery Endothelial Cells.” FASEB J 13 (1999): A502.
- Norwood N, Dean D, Moore T, Creighton J, Babal P, Stevens T. “Inhibition of Myosin Light Kinase Stimulates Calcium Release in Pulmonary Artery Endothelial Cells.” FASEB J 13 (1999): A502.
- Moore T, Norwood N, Brough G, Creighton J, Lee L, Babal P, Stevens T. “Calcium Influx Is Sufficient But Not Required For Thrombin-Induced Endothelial Cell Shape Change.” FASEB J 13 (1999): A501.
- Moore T, Norwood N, Brough G, Stevens T. “F-actin Gates Thapsigargin-Sensitive Store Operated Calcium Channels in Pulmonary Endothelial Cells.” FASEB J 12 (1998): A777.