Laura Gonzalez Bosc PhD

MSC08 4750
1 University of New Mexico
Albuquerque, NM 87131

Physical Location:
Biomedical Research Facility
237J

Phone: (505) 272-0605
Fax: (505) 272-6649

Associate Professor

Laura Gonzalez Bosc, Ph.D.

Research Interest

Laura Gonzalez Bosc

My research interest is study the role of the transcription factor, NFAT (nuclear factor of activated T cells), in the regulation of vascular smooth muscle phenotype and its implication in the development of high blood pressure within the lungs (pulmonary hypertension) associated with lung disease or residence at high altitude.  Chronic lung diseases such as emphysema, chronic bronchitis, cystic fibrosis and others cause poor oxygenation of the blood (hypoxia).  This can be very effectively mimicked by exposure to simulated altitude.  The result in both cases is the development of pulmonary hypertension, that can ultimately cause heart failure and death.

NFAT serves as a "master transcriptional regulator", interlinking Ca2+ signaling and other signaling pathways with the induction of specific genetic programs. NFAT is implicated in cardiac hypertrophy, vascular development, as well as smooth muscle differentiation.  NFAT regulates gene transcription in many different cell types but the target genes regulated by NFAT in vascular smooth muscle have not been clearly identified. Potential targets are the genes that encode smooth muscle contractile proteins and other genes related to modulation of smooth muscle phenotype. Continuous hypoxia results in pulmonary vasoconstriction, which leads to vascular remodeling. Vascular remodeling could be a beneficial adaptation of the vascular smooth muscle to increased intravascular pressure but alternatively may also be part of the mechanism that develops hypertension.  The complex process of vascular remodeling involves changes in the pattern of gene expression resulting in phenotypic switching of the smooth muscle cells from quiescent to proliferative.

Chronic hypoxia induces membrane potential depolarization of smooth muscle cells of pulmonary arteries increasing intracellular Ca2+ concentrations.  Since NFAT is a Ca2+ dependent transcription factor its transcriptional activity may be enhanced under this pathological condition.  To elucidate whether hypoxia induces NFAT activation, NFAT-luciferase reporter mice and confocal immunofluorescence microscopy are used to establish NFAT transcriptional activity and subcellular localization of the different NFAT isoforms.  To elucidate the target genes modulated by NFAT in smooth muscle cells from hypoxic pulmonary arteries NFATc3 knockouts and cyclosporine treated animals are used. 

We have demonstrated that NFATc3 is activated after chronic hypoxia exposure via endothelin-1/ETAR signaling. This activation requires RhoA/Rho kinase-mediated actin cytoskeleton remodeling. In addition, we have shown that NFATc3 is required for chronic hypoxia-induced pulmonary hypertension and pulmonary arterial remodeling. Our studies suggest that NFATc3 plays an important role as a regulator of transcription  in the development of pulmonary hypertension.

Education

College of Medicine. University of Vermont. UVM. Burlington, VT, USA.Department of PharmacologyPostdoctoral Fellow. Supervisor: Dr. Mark Nelson. 2001-2004.

School of Pharmacy and Biochemistry. University of Buenos Aires. UBA. Buenos Aires, Argentina. Biological Sciences. Doctor en la Universidad de Buenos Aires. Ph.DTitle: "Effect of different vasoactive substances on trans-epithelial ion transport." Advisor: Prof. Dr. N. A. Vidal. Grade: outstanding (Sobresaliente). 1996 - 2001

School of Pharmacy and Biochemistry. University of Buenos Aires UBA.  Buenos Aires, Argentina. Biochemistry. Orientation: Microbiology e Immunology. 1988 - 1995

School of Pharmacy and BiochemistryUBA. Buenos Aires, Argentina.Teacher with pedagogic formation in university teaching. Orientation: health sciences. 1995 - 1997



Professional Experience

1990 - 2000 Teaching Assistant. Cell Biology and Histology, College of Pharmacy and Biochemistry, University of Buenos Aires. Buenos Aires, Argentina.
1992 - 1994 Under-graduate Research Fellow. Cell Biology and Histology, College of Pharmacy and Biochemistry, University of Buenos Aires. Buenos Aires, Argentina.
1995 - 2000 Graduate Research Fellow. Cell Biology and Histology, College of Pharmacy and Biochemistry, University of Buenos Aires. Buenos Aires, Argentina.
2001 - 2002 Postdoctoral Associate. Department of Pharmacology. College of Medicine. University of Vermont. Burlington, VT, US.
2002 - 2004 Postdoctoral Fellow (AHA). Department of Pharmacology. College of Medicine. University of Vermont. Burlington, VT, US.
2004 - 2010 Assistant Professor. Department of Cell Biology and Physiology. College of Medicine. University of New Mexico, NM, US.
2010 - Present Associate Professor. Department of Cell Biology and Physiology. College of Medicine. University of New Mexico, NM, US.




Honors

1994 Award to the scientific and technological production. University of Buenos Aires, Argentina.
1995 Award to the scientific and technological production. University of Buenos Aires, Argentina.
1996 Short Term Research fellowship at Physiology, School of Sciences. University of Balearic Islands, Spain.
Award granted by Ibero-American Cooperation Institute, Embassy of Spain.
1995 Predoctoral Fellowship level I. University of Buenos Aires, Argentina.
1998 Predoctoral Fellowship level II. University of Buenos Aires, Argentina.
1999 Young investigator award. Merck Sharp & Dohme.
2000 Young investigator travel award. International Society of Hypertension. Chicago, US.
2000 Award of the XXVII Argentinean Congress of Cardiology. Argentinean Society of Cardiology, Argentina.
2002 Northeast Affiliate Postdoctoral Fellowship. American Heart Association, US.
2004 Northeast Affiliate Postdoctoral Fellowship. American Heart Association, US.
2004 Programa Ramon y Cajal. Ministerio de Educación y Ciencia. Spain. (Not accepted)
2004 Research Allocation Committee Award. University of New Mexico, NM, US.
2005 Scientist Development Award. American Heart Association, US
2007 APS/NIDDK Minority Travel Awards: Experimental Biology.
2007 Dalsemer Award. Biomedical Research Grant. American Lung Association.
2007 R01 from NIH for 5 years.
2010 Respiration Section New Investigator Award. American Physiological Society.




Current Lab Personnel

Dr. Juan Manuel Ramiro-Diaz, PhD (Postdoctoral Associate
Wieslawa Giermakowska, M.S. (Lab. Technician)








Publications

  1. María F. Albertoni Borghese, Layne M. Bettini Carlos H. Nitta, Sergio de Frutos, Mónica Majowicz, Laura V. Gonzalez Bosc. Aquaporin-2 Promoter Is Synergistically Regulated by Nitric Oxide and Nuclear Factor of Activated T Cells. Nephron Extra. 1:124–138, 2011. Open Access. Full text
  2. Bierer R, Nitta CH, Friedman JK, Codianni SJ, de Frutos S, Dominguez-Bautista JA, Howard TA, Resta TC, Gonzalez Bosc LV. NFATc3 Is Required for Chronic Hypoxia-induced Pulmonary Hypertension in Adult and Neonatal Mice. Am J Physiol Lung Cell Mol Physiol. 301(6):L872-80, 2011Full text
  3. Snow JB, Gonzalez Bosc LV, Kanagy NL, Walker BR, Resta TC. Role for PKC{beta} in Enhanced Endothelin-1-Induced Pulmonary Vasoconstrictor Reactivity Following Intermittent Hypoxia. Am J Physiol Lung Cell Mol Physiol. 301(5):L745-54, 2011.Full text
  4. de Frutos S, Ramiro-Diaz JM, Nitta CH, Sherpa ML, Gonzalez Bosc LV. Endothelin-1 contributes to increased NFATc3 activation by chronic hypoxia in pulmonary arteries. Am J Physiol Cell Physiol. 2011 301(2):C441-50. Full text
  5. Jackson-Weaver O, Paredes DA, Gonzalez Bosc LV, Walker BR, Kanagy NL. Intermittent Hypoxia in Rats Increases Myogenic Tone Through Loss of Hydrogen Sulfide Activation of Large-Conductance Ca2+-Activated Potassium Channels. Circ Res. 2011 108(12):1439-47.  Full text
  6. Hughes JM, Riddle MA, Paffett ML, Gonzalez Bosc LV, Walker BR. Novel Role of Endothelial BKCa Channels in Altered Vasoreactivity Following Hypoxia. Am J Physiol Heart Circ Physiol. 299(5):H1439-50, 2010. Full text
  7. Sergio de Frutos, Elizabeth Caldwell, Carlos H. Nitta, Nancy L. Kanagy, Jian Wang, Wei Wang, Mary K. Walker, Laura V. Gonzalez Bosc. NFATc3 contributes to intermittent hypoxia-induced arterial remodeling in mice. Am J Physiol Heart Circ Physiol. 299(2):H356-63, 2010. Full text
  8. Sami I. Said, Sayyed A. Hamidi, Laura Gonzalez Bosc. Asthma and Pulmonary Arterial Hypertension:Do They Share a Key Mechanism of Pathogenesis? European Respiratory Journal 35:730-734, 2010. Full text
  9. Lisa M. Nilsson-Berglund, Anna V. Zetterqvist, Jenny Nilsson-Öhman, Mikael Sigvardsson, Laura V. González Bosc, Maj-Lis Smith, Albert Salehi, Elisabet Agardh, Gunilla Nordin Fredrikson, Carl-David Agardh, Jan Nilsson, Brian R. Wamhoff, Anna Hultgårdh-Nilsson, Maria F. Gomez. Nuclear Factor of Activated T-cells regulates osteopontin expression in arterial smooth muscle in response to diabetes-induced hyperglycemia. Arterioscler Thromb Vasc Biol. 30(2):218-24, 2010. Full text
  10. Sergio de Frutos, Carlos H. Nitta, Elizabeth Caldwell, Jessica Friedman, Laura V. González Bosc. Regulation of Soluble Guanylyl Cyclase-α1 Expression in Chronic Hypoxia-induced Pulmonary Hypertension: Role of NFATc3 and HuR. Am J Physiol Lung Cellular and Molecular Physiology 297(3):L475-86, 2009. Full text
  11. Cherng TW, Campen MJ, Knuckles TL, Gonzalez Bosc LV, Kanagy NL. Impairment of coronary endothelial cell ETB receptor function following short-term inhalation exposure to whole diesel emissions. Am J Physiol Regul Integr Comp Physiol 297(3):R640-7, 2009. Full text
  12. Sergio de Frutos, Laura Duling, Dominique Alò, Tammy Berry, Olan Jackson-Weaver, Mary Walker, Nancy Kanagy, and Laura González Bosc. NFATc3 is required for intermittent hypoxia-induced hypertension. Am J Physiol Heart Circ Physiol 294: H2382–H2390, 2008. Full text
  13. Sergio de Frutos, Rhyannon Spangler, Dominique Alò, and Laura V. González Bosc. NFATc3 Mediates Chronic Hypoxia-induced Pulmonary Arterial Remodeling with α-Actin Up-regulation. JBC 282: (20) 15081–15089, 2007. Featured in NAVBO. Full text
  14. Jessica A. Filosa, Mark T. Nelson and Laura V. Gonzalez Bosc. Activity-dependent NFATc3 nuclear accumulation in pericytes from cortical parenchymal microvessels. Am J Physiol Cell Physiol 293: C1797–C1805, 2007.
  15. Laura V. Gonzalez Bosc, Jeff J. Layne, Mark T. Nelson, and David C. Hill-Eubanks. Nuclear Factor of Activated T Cells and Serum Response Factor Cooperatively Regulate the Activity of an α-Actin Intronic Enhancer. JBC 280: (28) 26113–26120, 2005. Full text
  16. Laura V. Gonzalez Bosc, Michael K. Wilkerson, Karen N. Bradley, Delrae M. Eckman, David C. Hill-Eubanks, and Mark T. Nelson. Intraluminal Pressure Is a Stimulus for NFATc3 Nuclear Accumulation: role of calcium, endothelium-derived nitric oxide, and cGMP-dependent protein kinase. JBC 279: (11) 10702–10709, 2004. Full text
  17. M.P. Majowicz, L.V. Gonzalez Bosc, M.F. Albertoni Borghese, M.F. Delgado, M.C. Ortiz, N. Sterin Speziale, N.A. Vidal. Atrial natriuretic peptide and endothelin-3 target renal sodium-glucose cotransporter. Peptides 24: 1971–1976, 2003. Full text
  18. Maria F. Gomez, Laura V. Gonzalez Bosc, Andra S. Stevenson, M. Keith Wilkerson, David C. Hill-Eubanks, and Mark T. Nelson. Constitutively Elevated Nuclear Export Activity Opposes Ca2+-dependent NFATc3 Nuclear Accumulation in Vascular Smooth Muscle: role of JNK2 and CRM-1. JBC 278: (47) 46847–46853, 2003. Full text
  19. L.V. González Bosc, M.P. Majowicz, M.C. Ortiz, N.A. Vidal. Effects of endothelin-3 on intestinal ion transport. Peptides 22: 2069–2075, 2001.
  20. Laura V. González Bosc, María L. Kurnjekb, Angélica Müller, Norberto A. Terragno and Nidia Basso. Effect of chronic angiotensin II inhibition on the nitric oxide synthase in the normal rat during aging. Journal of Hypertension 19: 1403–1409, 2001.
  21. L. González Bosc, Kurnjek ML, Müller A, Basso N. Effect of chronic angiotensin II inhibition on the cardiovascular system of the normal rat. American Journal of Hypertension 13: (12) 1301-1307, 2000.
  22. María de los Angeles Costa, Laura V. González Bosc, Mónica P. Majowicz, Norberto A. Vidal, Ana M. Balaszczuk, Cristina T. Arranz. Atrial Natriuretic Peptide Modifies Arterial Blood Pressure Through Nitric Oxide Pathway in Rats. Hypertension 35:1119-1123, 2000. Full text
  23. L. V. González Bosc, F. Capani, J. J. López-Costa,  M. C. Ortiz, M. P. Majowicz, M. A. Costa, C. T. Arranz, A. M. Balaszczuk, J. Pecci Saavedra and N. A. Vidal. Effect of atrial natriuretic peptide on nitric oxide synthase-NADPH-diaphorase in the rat intestinal tract. Peptides 20: 615-621, 1999.
  24. L. V. González Bosc, N. A. Vidal, R. Prieto and J. A. Tur. Effect of Atrial Natriuretic Peptide on a-Methyl-D-glucoside intestinal active uptake in rats. Peptides 19: 1249-1253, 1998.
  25. L.V. González Bosc, P.A. Elustondo, M.C. Ortiz and N.A. Vidal. Effect of atrial natriuretic peptide on sodium-glucose cotransport in the rat small intestine. Peptides 18: 1491-1495, 1997
  26. L. V.González Bosc, P. A. Elustondo and N.A. Vidal. Effect of Atrial Natriuretic Peptide on in vitro sodium absorption in the rat small intestine. Medicine Science Research 23: 759-61, 1995.

Reviews

  1. L. V. González Bosc y N.A. Vidal. El Péptido Auricular Natriurético: estructura y function. Rev. Cien (IEB) 19: 91-96, 1997. Invited.
  2. L. V. González Bosc, M. P. Majowicz and N. A. Vidal. Effects of Atrial Natriuretic Peptide in the Gut. Peptides21: 875-887, 2000. Invited.
  3. González Bosc LV, Resta T, Walker B, Kanagy NL. Mechanisms of intermittent hypoxia-induced hypertension. J Cell Mol Med. 14(1-2):3-17, 2010Full text