Department of Cell Biology and Physiology

Faculty

Laura Gonzalez Bosc, Ph.D.

Research Interests

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 will be 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 will be used. A candidate target is a-actin since NFATc3 isoform seems to cooperate with serum response factor (SRF) in regulating a-actin expression in smooth muscle cells in culture (Gonzalez Bosc et. al. 2004, submitted to JBC).  In addition, other potential targets may be other SRF-regulated smooth muscle contractile proteins, endothelin and potassium channels.

Since nothing is known about the role of NFAT in regulating vascular function in pulmonary hypertension, results derived from this study will provide insight on the role of this important regulator of gene transcription in this pervasive condition disease and in understanding the processes involved in the development of pulmonary hypertension.

Education

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

School of Pharmacy and Biochemistry. University of Buenos Aires. UBA. Buenos Aires, Argentina. Cell Biology. Doctor en la Universidad de Buenos Aires. Ph.D. Title: "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 Biochemistry. UBA. 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 - Present Assistant 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.

Current Lab Personnel

Dr. Sergio De Frutos Garcia, PhD (Postdoctoral Associate)

Tammy Berry, B.S. (Lab. Technician)

ONE OPEN POSITION FOR A GRADUATE STUDENT

ONE OPEN POSITION FOR A WORK STUDY OR STUDENT EMPLOYEE

Publications

  1. "Effect of Atrial Natriuretic Peptide on in vitro sodium absorption in the rat small intestine." L. V.González Bosc, P. A. Elustondo and N.A. Vidal. Medicine Science Research 23: 759-61, 1995.
  2. "Effect of atrial natriuretic peptide on sodium-glucose cotransport in the rat small intestine." L.V. González Bosc, P.A. Elustondo, M.C. Ortiz and N.A. Vidal. Peptides 18, 10, 1491-1495, 1997.
  3. "Effect of Atrial Natriuretic Peptide on a-Methyl-D-glucoside intestinal active uptake in rats."L. V. González Bosc, N. A. Vidal, R. Prieto and J. A. Tur. Peptides 19, 1249-1253, 1998.
  4. "Effect of atrial natriuretic peptide on nitric oxide synthase-NADPH-diaphorase in the rat intestinal tract". 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. Peptides 20, 5, 615-621, 1999.
  5. "Atrial Natriuretic Peptide Modifies Arterial Blood Pressure through Nitric Oxide pathway in Rats." M. A. Costa, L. V. González Bosc, M. P. Majowicz, N. A. Vidal, A. M. Balaszczuk and C. T. Arranz. Hypertension 35, 1119-1123, 2000.Full text
  6. "Effect of renin-angiotensin sysem inhibition (RASI) on the aging process of the normal rat.." L. González Bosc, M. L. Kurnjek, N. Paglia and N. Basso. American Journal of Hypertension 13,12, 1301-1307, 2000.
  7. "Effects of Atrial Natriuretic Peptide in the Gut." L. V. González Bosc, M. P. Majowicz and N. A. Vidal. Peptides 21, 6, 875-887, 2000 (Invited review).
  8. "Effect of Chronic Angiotensin II Inhibition on the Nitric Oxide Synthase in the Normal Rat  during Aging." L. V. González Bosc, M. L. Kurnjek, A. Müller, N. A. Terragno and N. Basso. Journal of Hypertension, 19, 8, 1403-1409, 2001.
  9. "Effect of Endothelin 3 on small intestinal ion transport." L. V. González Bosc, M. P. Majowicz, M. C. Ortiz and N. A. Vidal. Peptides, 22, 2069-2075, 2001.Full text.
  10. "Constitutively elevated nuclear export activity opposes Ca2+-dependent NFATc3 nuclear accumulation in vascular smooth muscle: Role of JNK2 and Crm-1." M.F. Gomez, L.V. Gonzalez Bosc, A.S. Stevenson, M.K. Wilkerson, D.C. Hill-Eubanks and M.T. Nelson. JBC, 278(47), 46847-46853, 2003.Full text.
  11. "Atrial natriuretic peptide and endothelin- 3 target renal sodium-glucose cotransporter." M. P. Majowicz, L. V. Gonzalez Bosc, M. F. Albertoni Borghese, M. F. Delgado, M. C. Ortiz, N. Sterin Speziale and N.A. Vidal. Peptides, 24, 1971-1976, 2003.Full text.
  12. "Intraluminal pressure is a stimulus for NFATc3 nuclear accumulation: role of smooth muscle calcium and endothelium-derived nitric oxide." L. V. Gonzalez Bosc, M. K. Wilkerson, D. M. Eckman, K. N. Bradley, D.C. Hill-Eubanks, M. T. Nelson. JBC 279 (11), 10702-10709. 2004. Featured in Science's Signal Transduction Knowledge Environment (STKE), Vol. 2004, Issue 224, page 95, 2004.Full text.
  13. "Nuclear Factor of Activated T-cells and Serum Response Factor cooperatively regulate the enhancer activity of a CArG box-containing a-actin intronic element." L. V. Gonzalez Bosc, J. Layne, M. T. Nelson, and D. Hill-Eubanks. JBC 280 (28), 26113-20. 2005. Full text.
  14. "NFATc3 mediates chronic hypoxia-induced pulmonary arterial remodeling with alpha-actin up-regulation". de Frutos S, Spangler R, Alo D, Gonzalez Bosc LV. JBC 282 (20), 15081-9, 2007. Full text.

  15. "Activity-dependent NFATc3 nuclear accumulation in pericytes from cortical parenchymal microvessels".  Filosa JA,  Nelson MT, Gonzalez Bosc LV. AJP-Cell Physiol 293: C1797–C1805, 2007. Full text.