Cell Differentiation and Pathology

PROFILE

Our laboratory works to understand the molecular mechanisms that regulate skeletal muscle formation and how they are affected in skeletal muscular dystrophies. Our laboratory has conducted extensive studies to understand the role of extracellular matrix (ECM) in skeletal muscle formation and regeneration and the comprehension of the fibrotic phenomena associated with skeletal muscular dystrophies.
We are interested in the understanding of the mechanisms involved in fibrosis associated with skeletal muscular diseases. Fibrosis corresponds to an increase in ECM constituents, which occurs in skeletal muscular dystrophies such as Duchenne Muscular Dystrophy (DMD), denervation, or loss of motor neuron activity (ALS). We study the role of profibrotic factors (TGF-, CTGF/CCN2), different components of the renin-angiotensin-system (RAS), and lysophosphatidic acid LPA in the genesis of skeletal muscle fibrosis. Also, we are interested in understanding the cell type(s) responsible for the fibrotic response in the different muscular models.

Correo electrónico: ebrandan@cienciavida.org

LAB MEMBERS

Research Head: Enrique Brandan

Doctoral Students: Adriana Córdova • Meilyn Cruz • Felipe Gallardo
Undergraduate Students: Alexia Bock
Research Assistants: Eduardo Ramirez • Darling Vera
Postdoctoral Fellows: Lina Correa

COLLABORATIONS

National Collaborations:
• Dra. María José Acuña (Universidad Bernardo O´Higgins)
• Dr. Claudio Cabello (Universidad Andrés Bello)
• Dra. Verónica Eisner (P. Universidad Católica de Chile)

International Collaboration:
• Dr. Roel Goldschmeding (Utrecht University, The Netherlands)
• Dr. Kenneth E. Lipson (FibroGen, USA)
• Dr. Fabio Rossi (University of British Columbia, Canada)

FORMER LAB MEMBERS

Ph.D. students:
María José Acuña, Ph.D. Curr. Pos. Assistant Professor, Universidad Bernardo O’Higgins, Santiago, Chile
Claudio Cabello-Verrugio, Ph.D. Curr. Pos. Full Professor, Universidad Andrés Bello, Santiago, Chile
Daniel Cabrera, Ph.D. Curr. Pos. Research Associate, P. Universidad Católica de Chile, Santiago, Chile
Juan Carlos Casar, MD/Ph.D. Curr. Pos. Assistant Professor, P. Universidad Católica de Chile, Santiago, Chile
Rebeca Droguett, Ph.D. Curr. Pos. Teacher in Science, Santiago, College, Santiago, Chile
Jaime Gutierrez, Ph.D. Curr. Pos. Associate Professor, Universidad San Sebastián, Santiago, Chile
Juan Pablo Henríquez, Ph.D. Curr. Pos. Full Professor, Universidad de Concepción, Concepción, Chile
Claudia Hurtado, Ph.D. Curr. Pos. Research Associate. Clínica Las Condes, Santiago, Chile
Juan Larraín, Ph.D. Curr. Pos. Full Professor, P. Universidad Católica de Chile, Santiago, Chile
Valeria Mezzano, M.D./Ph.D. Curr. Pos. Assistant Professor, NYU Langone Medical Center, USA
María Gabriela Morales, Ph.D. Curr. Pos. Research Associate, University of Texas Southwestern M.C. USA
Hugo Olguín, Ph.D. Curr. Pos. Associate Professor, P. Universidad Católica de Chile, Santiago, Chile
Nelson Osses, Ph.D. Curr. Pos. Full Professor, Universidad Católica de Valparaiso, Valparaíso, Chile
Cecilia Riquelme, Ph.D. Curr. Pos. Associate Professor, P. Universidad Católica de Chile, Santiago, Chile
Cecilia Vial, Ph.D. Curr. Pos. Associate Professor, Universidad del Desarrollo, Santiago, Chile.
Gonzalo Cordova, Ph.D. Curr. Pos. Scientific Editor Springer Nature B.V. Rotterdam, The Netherlands
Andrés Ramirez, Ph.D. Curr. Pos. Regional Specialist. United Arab Emirates
David Gonzalez, Curr. Pos. Postdoctoral Fellow. Institut des Neurosciences de Montpellier, France
Osvaldo Contreras, Ph.D. Victor Chang Cardiac Research Institute, Darlinghurst, Australia
Roger Valle-Tenney, Université Catholique de Louvain, Belgium.
Adriana Córdova, Ph.D.(c). P. Universidad Católica de Chile
Meilyn Cruz, Ph.D.(c). P. Universidad Católica de Chile
Felipe Gallardo, Graduate student, P. Universidad Católica de Chile

Postdoctoral Fellows:
Claudio Cabello-Verrugio, Ph.D. Curr. Pos. Full Professor, Universidad Andrés Bello, Santiago, Chile
Daniel Cabrera, Ph.D. Curr. Pos. Research Associate, P. Universidad Católica de Chile, Santiago, Chile
Cristián Droppelmann, Ph.D. Curr. Pos. Reasearch Associate, The University of Western Ontario, Canada
Verónica Eisner, Ph.D. Curr. Pos. Assistant Professor, P. Universidad Católica de Chile, Santiago, Chile
Jaime Gutiérrez, Ph.D. Curr. Pos. Associate Professor, Universidad San Sebastián, Santiago, Chile
Daniela Rebolledo, Ph.D. Independent Researcher, CEBIMA, Punta Arenas, Chile.
Cecilia Riquelme, Ph.D. Curr. Pos. Associate Professor, P. Universidad Católica de Chile, Santiago, Chile
Cecilia Vial, Ph.D. Curr. Pos. Associate Professor, Universidad del Desarrollo, Santiago, Chile.
Joan Villena, Ph.D. Curr. Pos. Assistant Professor, Universidad de Valparaíso, Valparaíso, Chile
Gonzalo Ugarte, Ph.D. Curr. Pos. Associate Professor, Universidad de Santiago, Santiago, Chile

SELECTED PUBLICATIONS

  • Contreras, O., Soliman, H., Theret, M., Rossi, F.M., and Brandan, E. (2020) TGF--driven downregulation of the Wnt/b-Catenin transcription factor TCF7L2/TCF4 in PDGFRa+ fibroblasts. J. Cell Sci. 133(12):jcs242297. doi: 10.1242/jcs.242297 | PDF | ABSTRACT
  • Valle-Tenney R, Rebolledo D, Acuña MJ, Brandan E. (2020) HIF-hypoxia signaling in skeletal muscle physiology and fibrosis. J Cell Commun Signal. 14: 147-158. | PDF | ABSTRACT
  • Valle-Tenney R, Rebolledo D, Lipson KE, Brandan E. (2019) Role of hypoxia in skeletal muscle fibrosis: Synergism between hypoxia and TGF-β signaling upregulates CCN2/CTGF expression specifically in muscle fibers. Matrix Biol. 87: 48-65. | PDF | ABSTRACT
  • Contreras, O., Cruz-Soca, M., Theret, M., Soliman, H., Groppa, H., Wei, L., , Rossi, F.M., and Brandan, E. (2019) TGF-β and PDGFRα signaling pathways cross-talk regulates stromal fibro/adipogenic progenitors’ differentiation. J. Cell Sci doi: 10.1242/jcs.232157 | PDF | ABSTRACT
  • Contreras, O., Rossi, F.M., and Brandan, E. (2019) Adherent muscle connective tissue fibroblasts are phenotypically and biochemically equivalent to stromal fibro/adipogenic progenitors. Matrix Biol Plus doi.org/10.1016/j.mbplus.2019.04.003 | PDF | ABSTRACT
  • Rebolledo, D.L., González, D., Faundez-Contreras, J., Contreras, O., Murphy-Ullrich, J.E., Lipson, K.E. and Brandan, E. (2019) CTGF/CCN2 Modulates Denervation-induced Skeletal Muscle Fibrosis independently of TGF- Matrix Biol. doi: 10.1016/j.matbio.2019.01.002 | PDF | ABSTRACT
  • Gonzalez, D and Brandan, E (2019) CTGF/CCN2 from skeletal muscle to nervous system: impact on neurodegenerative diseases. Mol. Neurobiol. In Press doi.org/10.1007/s12035-019-1490-9 | PDF | ABSTRACT
  • Gonzalez, D., Rebolledo, D.L., Correa, L.M., Court, F., Cerpa, W., Lipson, K.E. Zundert, B.V. and Brandan, E. (2018) The inhibition of CTGF/CCN2 activity improves muscle and locomotor function in a murine ALS model. Hum. Mol. Gen. 27: 2913-2926 | PDF | ABSTRACT
  • Contreras, O., Villarreal, M. and Brandan, E. (2018) Nilotinib impairs skeletal myogenesis by increasing myoblast proliferation. Skeletal Muscle 20, 8(1):5. doi: 10.1186/s13395-018-0150-5 | PDF | ABSTRACT
  • Riquelme-Guzmán, C., Contreras, O., and Brandan E. (2018) Expression of CTGF/CCN2 in response to LPA is stimulated by fibrotic extracellular matrix via the integrin/FAK axis. Am. J. Physiol. Cell Physiol. 314: C415–C427. | PDF | ABSTRACT
  • Acuña, MJ., Salas, D., Cordova-Casanova, A., Cruz-Soca, A., Céspedes, C, Vío, C.P. and Brandan, E (2017) Blockade of Bradykinin receptors worsens the dystrophic phenotype of mdx mice: differential effects for B1 and B2 receptors. J Cell Commun Signal. doi: 10.1007/s12079-017-0439-x | PDF | ABSTRACT
  • Gonzalez, D., Contreras, O., Rebolledo, DL., Espinoza, JP., van Zundert, B., Brandan E. (2017) ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers. PLoS One 16;12(5):e0177649. doi:10.1371/journal.pone.0177649. | PDF | ABSTRACT
  • Morales, M.G., Acuña, M.J., Cabrera, D., Goldschmeding, R and and Brandan E. (2018) The profibrotic connective tissue growth factor (CTGF/CCN2) correlates with the number of necrotic-regenerative foci in dystrophic muscle. J Cell Commun Signal. 12: 413-421. | PDF | ABSTRACT
  • Cabrera, D., Wree, A., Povero, D., Solis, N., Hernandez, A., Pizarro, A, Moshage, H., Torres, J., Feldstein, A., Cabello-Verrugio, C., Brandan, E., Barrera, F., Arab, J. Arrese, M. (2017) Andrographolide ameliorates inflammation and fibrogenesis and attenuates inflammasome activation in experimental non-alcoholic steatohepatitis. Sci Rep. 14, 7(1):349.1doi: 10.1038/s41598-017-03675-z. | PDF | ABSTRACT
  • Contreras O, Brandan E. (2017) Fibro/adipogenic progenitors safeguard themselves: a novel mechanism to reduce fibrosis is discovered. J Cell Commun Signal. 11: 77-78. | PDF | ABSTRACT