MIPS Faculty

Beatriz Gonzalez-Flecha

Associate Professor of Molecular Biology and Environmental Health
Department of Environmental Health

Building II, Room 213
Environmental Health
665 Huntington Avenue
Boston MA 02115
phone: 617-432-1277
Email: bgonzale@hsph.harvard.edu
Education

    Ph.D. , 1991, University of Buenos Aires, Argentina
    M.S. , 1987, University of Buenos Aires, Argentina.

Research Interests:

    Molecular oxygen is essential and toxic for aerobic organism. Oxygen toxicity is due to chemical species derived from its partial reduction (reactive oxygen species -ROS: superoxide anion, hydrogen peroxide and hydroxyl radical). These highly reactive species are normally produced in cells is association to electron-transfer processes and respiration and kept at sub-toxic levels by the action of specific antioxidant enzymes. Nonetheless, the level of oxygen free radicals in a cell can be increased by intra or extracellular stimuli, leading to oxidation of key cell components in a process termed oxidative stress. Oxidative stress has been associated with carcinogenesis, aging, atherosclerosis and Alzheimer's disease and cell damage due to ischemia-reperfusion, xenobiotics metabolism, UV irradiation and many other environmental diseases.

    The toxic effects of air pollution are widely documented. In recent years, however, there has been an increasing interest in the study of the health effects of particulate matter (PM), a previously unexplored constituent of urban air pollution. Exposure to increased levels of PM of respirable size is strongly and consistently associated with increased cardiopulmonary morbidity and mortality. Conversely, improved air quality appears to correlate with decrease mortality. Particulate matter is a mixture of inorganic and organic components that vary in size, origin, and composition. The mechanisms of PM health effects are still poorly understood. However, studies in cellular and animal models suggest a variety of possible mechanisms including direct effects of particle components on the intracellular sources of ROS, indirect effects due to pro-inflammatory mediators released from PM-stimulated macrophages, and neural stimulation after particle deposition in the lungs.

    Our current research centers on the characterization of the mechanisms leading to to the cardiopulmonary effects of ambient air particles with a focus on the role of ROS in the mechanisms of toxicity by PM.We have also developed an in vitro system to study specific responses affecting alveolar epithelial cells, a sensitive target for PM. Lung epithelial cells respond to particles with increases in their intracellular concentrations of ROS, increased production and release of pro-inflammatory cytokines (IL-8 and MIP-2), and for some CAPs samples, with increased apoptosis and necrosis. Our current work is focused on the study of the mechanisms regulating the fate of alveolar epithelial cells between proliferation or apoptosis after exposure to particulate (PM) or soluble (hydrogen peroxide) oxidants.

Publications:

    Gurgueira, S.A., Lawrence, J., Coull, B., Krishna-Murthy, G.G., and Gonz?lez-Flecha, B. Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation. Environ. Health Perspect., 110: 749-755, 2002.

    Radisavljevic Z. and Gonz?lez-Flecha, B. H2O2 signaling through a pathway involving Cdk2, importin-alpha and NuMA protein is essential for mitosis. Biochim. Biophys. Acta. 1640: 163-170, 2003.

    Radisavljevic Z., Gonz?lez-Flecha, B. TOR kinase and Ran are downstream from PI3K/Akt in H2O2-induced mitosis. J. Cell. Biochem. 91: 1293-1300, 2004.

    Rhoden, C.R., Lawrence, J., Godleski, J.J., Gonz?lez-Flecha, B. N-acetylcysteine prevents lung inflammation after short-term inhalation exposure to concentrated ambient particles Toxicol. Sci. 79: 296-303, 2004.

    Carvalho, H., Evelson, P. Sigaud, S. and Gonz?lez-Flecha, B. Role of mitogen-activated protein kinases in apoptosis induced by hydrogen peroxide in primary alveolar epithelial cells. J. Cell. Biochem. 92: 502:513, 2004.

    Sigaud, S., Evelson, P., Gonz?lez-Flecha, B. H2O2-induced proliferation of primary alveolar epithelial cells is mediated by MAP kinases. Antioxidants and Redox Signaling 7:6-13, 2005.

    Yin, L., Stearns, R., Gonz?lez-Flecha, B. Lysosomal and mitochondrial pathways in H2O2-induced apoptosis of alveolar type II cells. J. Cell. Biochem. 94:433-445, 2005.

    Rhoden, C.R., Wellenius, G., Ghelfi, E., Lawrence, J., Gonz?lez-Flecha, B. PM-Induced Cardiac Oxidative Stress Is Mediated by Autonomic Stimulation. Biochim Biophys Acta. 1725: 305-313, 2005.

    Hatzis,C., Godkleski,JJ., Gonz?lez-Flecha, B, Wolfson,J.M., Koutrakis, P. Ambient Particulate Matter Exhibits Direct and Selective Inhibitory Effects on Oxidative Stress Enzymes. Environ. Sci. Technol. 40: 2805-2811, 2006.

Websites