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Maria Paz Marzolo Canales

Profesor Titular

PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE, FAC. CIENCIAS BIOLOGICAS, DEPTO. BIOLOGIA

Santiago, Chile

Líneas de Investigación


Intracellular protein trafficking, epithelial cells, neurons, and Schwann cells. Studies on the low-density lipoprotein receptor (LDL-R) family, including LRP1, LRP2, and ApoER2. Reelin signaling pathway and its physiologic roles in health and diseas

Educación

  •  Cell and Molecular Biology, PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE. Chile, 1997
  •  Biochemistry, PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE. Chile, 1988

Experiencia Académica

  •   Asistant Professor Full Time

    UNIVERSIDAD DE CHILE

    Facultad de Ciencias

    Santiago, Chile

    1999 - 2002

  •   Investigador Asociado Full Time

    PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE

    Medicina

    Santiago, Chile

    1988 - 1989

  •   Postdoctoral Full Time

    WASHINGTON UNIVERSITY IN ST. LOUIS

    St. Louis MO, Estados Unidos

    1998 - 1999

  •   Post Doctoral Full Time

    WASHINGTON UNIVERSITY IN ST. LOUIS

    St. Louis MO, Estados Unidos

    1998 - 1999

  •   Postdoctoral fellow Full Time

    PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE

    Ciencias Biológicas

    Santiago, Chile

    1997 - 1998

  •   Profesor Asistente Full Time

    PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE

    Ciencias Biologicas

    Santiago, Chile

    2002 - 2005

  •   Visiting Professor Other

    University of Bristol

    Bristol, Reino Unido

    2017 - 2017

  •   Visiting Researcher Full Time

    NATIONAL INSTITUTE OF HEALTH

    Bethesda, Estados Unidos

    2017 - 2018

  •   Profesor Asociado Full Time

    PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE

    Ciencias Biológicas

    Santiago, Chile

    2005 - 2021

  •   Profesor Titular Full Time

    PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE

    Ciencias Biológicas

    Santiago, Chile

    2021 - A la fecha

Experiencia Profesional

  •   Director Nucleo Milenio en Biología Regenerativa Part Time

    Instituto MIlenio

    Santiago, Chile

    2010 - 2012

  •   Miembro Grupo Estudios Biologia 2, Director 2013 Part Time

    FONDECYT

    Santiago, Chile

    2011 - 2013

  •   Miembro Panel Grupo Estudios Biologia 2 Part Time

    FONDECYT

    Santiago, Chile

    2015 - 2015

Formación de Capital Humano


Undergraduate and Master Thesis Direction (Finished)

1. Benjamín Erranz. “Expresión y función de megalina en epitelio vesícula biliar humana y de ratón”. Ingeniería en Biotecnología Molecular U. Chile, 2004.

2. Maribel Donoso. “Determinantes moleculares del tráfico de LRP en células epiteliales polarizadas”. Ingeniería en Biotecnología Molecular U. Chile. 2005

3. Ricardo Matute. “Determinantes moleculares y celulares del tráfico endocítico y polaridad del ApoER2”. Bioquímica U. Chile. 2005

4. Pamela Farfán. “Generación de minireceptores de megalina para estudios del tráfico y función del receptor”. Ingeniería en Biotecnología Molecular, U. Chile 2007

5. Loreto Cuitiño. “Modulación del tráfico endocítico y función de ApoER2 por asociación a cavéolas”. Bioquímica Pontificia Universidad Católica de Chile, 2005.

6. Natalia Villatoro“Papel del ApoER2 en la modulación de c-abl”. Bioquímica y Química y Farmacia, Pontificia Universidad Católica de Chile, 2005 (*).Co-tutor, Dra. Alejandra Alvarez

7. Bárbara Ramos “Regulación de la expresión de megalina por FXR and PPAR”. Bioquímica P. Universidad Católica de Chile, 2008

8. Ignacio Cancino. “Papel del ApoER2 en la modulación de c-abl”. Biología BIO296 Pontificia Universidad Católica de Chile 2003 (*)Co-tutor, Dra. Alejandra Alvarez

9. Daniela Diaz Silva: “Participación de Megalina en la resistencia al desarrollo de Litiasis Biliar ratones con distinta susceptibilidad a la litiasis”. Bioquímica, U. Austral de Chile 2007.

10. Felipe Cabezas “Regulación de la expresión de megalina por TGFbeta”, Tesis de Bioquímico Pontificia Universidad Católica de Chile 2010,

11 María Luisa Benítez: “Regulation of signaling and processing of ApoER2 in the Niemann-Pick condition type C” Magister en Bioquimica, Pontificia Universidad Católica de Chile, 2011

11. Jorge Larios “Regulación del procesamiento proteolítico de ApoER2 y la conversación cruzada con receptores de neurotrofinas” Tesis de Bioquímico, PUC (* co-tutor Dra. Francisca Bronfman). Mayo 2012

12. Joaquín Cerda, “Role of ApoER2 in regeneration of the peripheral nervous system (PNS) after nerve damage". Bioquimico PUC (*co-tutor, Dr. Felipe Court). Noviembre 2012
13. Stefanie Teuber “Señalización y tráfico del receptor Gpbar1 en células epiteliales polarizadas de vesícula biliar”. Bioquímico: U. Austral de Chile Agosto 2013

14. Fernanda Navarro Aguad “LA VIA DE DEGRADACION DE APOER2 Y SUS FRAGMENTOS CARBOXILO TERMINAL SON DEPENDIENTES DE LISOSOMA Y UBIQUITINACION Y MODULADA POR SU LIGANDO REELINA”. Biotecnólogo Molecular, Universidad de la Frontera, Marzo 2014

15. Maria Karla Ramirez Viña. “Evaluación de la interacción de ApoER2 con el adaptador endosomal SNX27”. Tesis de Bioquímico, PUC. Septiembre 2014.

16. Francisca Rojo. "BÚSQUEDA DE UNA PROTEÍNA TIPO REELINA EN Drosophila melanogaster Y SU VÍA DE SEÑALIZACIÓN ASOCIADA", Tesis de Bioquimico PUC, Agosto 2018

PhD Thesis Direction (Finished)

1. Maria Isabel Yuseff S. “Megalin and new study model for novel trafficking aspects in polarized epithelial cells”. U. Chile. 2005.

2. Jessica Scheu T. “Disabled-2 regulates Wnt signaling by its endocytosis function”, PUC (Co-tutoria, Dr. Nibaldo Inestrosa, 2009).

3. Lisette Sandoval: “OCRL1 regula el tráfico de Megalina a través de la fosforilación de GSK3” 2013. PUC.

Postdoctoral Fellows (Finished)

1. Dr. Rodrigo Fuentealba: “Role of ApoER2 in APP processing and trafficking”, 2004, 2005. Actual Position University of Los Andes

2. Dr. Pablo Sotelo: “Role of sorting nexin 17 (SNX17) in ApoER2 trafficking, processing and function”. 2007-Dec 2009. Actual Position Departamento de Biotecnologia, Facultad de Ciencias Qu?micas, Universidad Nacional de Asuncion, Paraguay

3. Dra. María Consuelo Pastén. Fondecyt grant ”Participación de ApoER2, su ligando Reelina y las GTPasas monoméricas de la familia Rho en la migración de la célula de Schwann: implicancias en regeneración axonal periférica”. March2012-Dec 2014

5. Dr. Ignacio Jausoro. Reelina y ApoER2 regulan tráfico de proteínas de membrana y activación de Tc10 en neuronas hipocampales y DRG. Abril 2014


Difusión y Transferencia


2006 Organizer and Speaker, Chilean INTERNATIONAL SYMPOSIUM "LIPOPROTEIN RECEPTORS: FROM CELL BIOLOGY TO DISEASE". FONDAP Center for Cell Regulation and Pathology, CRCP. (2006), Santiago Chile
2009- Member of the selection committee for national fellowships for PhD students, CONICYT
2010 Organizer and speaker: Symposium at the XXIV Annual meeting for the Chilean Cell Biology Society. “NEW INSIGHTS IN THE PROTEOLYTIC PROCESSING BY SECRETASES; CELL BIOLOGY, REGENERATION AND ALZHEIMER’S DISEASE.

2011-15 Member of the Biology 2 Study Section FONDECYT
2013-14 Director of the Biology 2, Study Section FONDECYT.
2010- Editorial Board, “Molecular Neurodegeneration”
2013- Editorial Board, “Biochemical Journal”
2013- Editorial Board of “World Journal of Biochemical Chemistry”

2014 Organizer of the EMBO workshop “Current advances in membrane trafficking: Implications
for polarity and diseases” Puerto Natales, September 2014
2016 Organizer of the EMBO workshop “Actualization in membrane trafficking in health and disease”, La Serena, September 2016

Society Memberships:
Chilean Society for Cell Biology; Chilean Society for Biology; Chilean Society for Neurosciences
American Society for Cell Biology (ASCB), International Society of Neurochemistry (ISN)


Premios y Distinciones

  •   Frontier Science Program Member

    ACADEMIA CHILENA DE CIENCIAS

    Chile, 2004

    Distinción entregada por la Academia Chilena de Ciencias a científicos jovenes de distintas disciplinas

  •   Beca de Honor

    PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE

    Chile, 1981

    Beca entregada por la PUC por el mejor estudiante de su promoción (Bioquímica)

  •   Beca de Honor

    PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE

    Chile, 1986

    Beca entregada por la PUC al mejor estudiante de su promoción (bioquímica)

  •   Mejor Tesis de Doctorado en Biología Celular

    Fundación Chilena para la Biología Celular

    Chile, 1997

    Premio entregado por la Fundación Chilena para la Biología Celular por la mejor Tesis de doctorado


 

Article (49)

An update on cellular and molecular determinants of Parkinson's disease with emphasis on the role of the retromer complex
Reelin activates the small GTPase TC10 and VAMP7 to promote neurite outgrowth and regeneration of dorsal root ganglia (DRG) neurons
Golgi Complex Dynamics and Its Implication in Prevalent Neurological Disorders
Participation of the SMAD2/3 signalling pathway in the down regulation of megalin/LRP2 by transforming growth factor beta-1
TLR Crosstalk Activates LRP1 to Recruit Rab8a and PI3K gamma for Suppression of Inflammatory Responses
Interfering of the Reelin/ApoER2/PSD95 Signaling Axis Reactivates Dendritogenesis of Mature Hippocampal Neurons
The fast-recycling receptor Megalin defines the apical recycling pathway of epithelial cells
A RhoA Signaling Pathway Regulates Dendritic Golgi Outpost Formation
ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1
EMBO Workshop al fin del mundo: a meeting on membrane trafficking and its implication for polarity and diseases
Neurotrophins regulate ApoER2 proteolysis through activation of the Trk signaling pathway
Rho GTPases at the crossroad of signaling networks in mammals: impact of Rho-GTPases on microtubule organization and dynamics
Sorting Nexin 17 Regulates ApoER2 Recycling and Reelin Signaling
The p75 neurotrophin receptor evades the endolysosomal route in neuronal cells, favouring multivesicular bodies specialised for exosomal release
A Sorting Nexin 17-Binding Domain Within the LRP1 Cytoplasmic Tail Mediates Receptor Recycling Through the Basolateral Sorting Endosome
alpha-Secretase-derived Fragment of Cellular Prion, N1, Protects against Monomeric and Oligomeric Amyloid beta (A beta)-associated Cell Death
Novel aspects of the apolipoprotein-E receptor family: regulation and functional role of their proteolytic processing
Megalin/LRP2 Expression Is Induced by Peroxisome Proliferator-Activated Receptor -Alpha and -Gamma: Implications for PPARs' Roles in Renal Function
New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression
OCRL controls trafficking through early endosomes via PtdIns4,5P(2)-dependent regulation of endosomal actin
Lipoprotein receptors and cholesterol in APP trafficking and proteolytic processing, implications for Alzheimer's disease.
Polarized Traffic of LRP1 Involves AP1B and SNX17 Operating on Y- dependent Sorting Motifs in Different Pathways
Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes
Protein kinase D regulates trafficking of dendritic membrane proteins in developing neurons
A cytoplasmic PPPSP motif determines Megalin's phosphorylation and regulates receptor's recycling and surface expression
ApoER2 expression increases A beta production while decreasing Amyloid Precursor Protein (APP) endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of gamma-secretase activity
Apical distribution of HFE-beta 2-microglobulin is associated with inhibition of apical iron uptake in intestinal epithelia cells
The low density lipoprotein receptor-related protein functions as an Endocytic receptor for decorin
ApoER2 is endocytosed by a clathrin-mediated process involving the adaptor protein Dab2 independent of its rafts' association
Megalin and cubilin expression in gallbladder epithelium and regulation by bile acids
Signal transduction during amyloid-beta-peptide neurotoxicity: role in Alzheimer disease
Differential distribution of low-density lipoprotein-receptor-related protein (LRP) and megalin in polarized epithelial cells is determined by their cytoplasmic domains
A role for megalin's proline-rich motif in its endocytic trafficking and cytoskeleton association
Differential functions of members of the low density lipoprotein receptor family suggested by their distinct endocytosis rates
High affinity binding of receptor-associated protein to heparin and low density lipoprotein receptor-related protein requires similar basic amino acid sequence motifs
Identification of a major cyclic AMP-dependent protein kinase A phosphorylation site within the cytoplasmic tail of the low-density lipoprotein receptor-related protein: Implication for receptor-mediated endocytosis
Expression of alpha(2)-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP) in rat microglial cells
Role of RAP in the biogenesis of lipoprotein receptors
The YXXL motif, but not the two NPXY motifs, serves as the dominant endocytosis signal for low density lipoprotein receptor-related protein
Mannose receptor is present in a functional state in rat microglial cells.
Cellular and molecular basis of estrogen's neuroprotection - Potential relevance for Alzheimer's disease
Apical sorting of hepatitis B surface antigen (HBsAg) is independent of N-glycosylation and glycosylphosphatidylinositol-anchored protein segregation.
Hepatic production of very low density lipoprotein, catabolism of low density lipoprotein, biliary lipid secretion, and bile salt synthesis in rats fed a bean (Phaseolus vulgaris) diet.
Influence of different dietary constituents of beans (Phaseolus vulgaris) on serum and biliary lipids in the rat
Efectos rápidos de una dieta rica en leguminosas sobre la concentración de colesterol plasmático en jovenes chilenos
Secretion of biliary lipids from the hepatocyte.
[Characterization of lipoprotein catabolism in biliary cholesterol hypersecretion conditions in rats].
Effect of bean intake on biliary lipid secretion and on hepatic cholesterol metabolism in the rat
Effect of bean intake on biliary lipid secretion and on hepatic cholesterol metabolism in the rat.

Abstract (11)

ApoER2 and Its Ligand Reelin Follow a Clathrin-Independent Endocytosis
Inhibition of the reelin signaling pathway promotes dendritogenesis in mature hippocampal neurons.
Defining a Sorting nexin 17-binding cluster, within the LRP1 cytoplasmic tail, and its role in receptor recycling in polarized and non-polarized cells
p75 neurotrophin receptor evades the endolysosomal route, favoring multivesicular bodies specialized for exosomal release in neuronal cells
Evidence for the involvement of LIMK1, PKD1 and BARS in Golgi outpost formation
LDL receptor-related protein (LRP) is an endocytic receptor for decorin and participates in a novel regulatory mechanism of TGF beta signaling by decorin
Molecular and cellular determinants of LDL-receptor related protein (LRP) trafficking and sorting in hippocampal neurons
ApoER2 associates to different lipid rafts depending on the cell context and is endocytosed by a clathrin-mediated process involving Dab2
Functional characterization of the endocytic and phosphorylation motifs of Megalin
Differential functions of members of the LDL receptor family suggested by their distinct endocytosis rates
High affinity binding of receptor-associated protein to heparin and LDL receptor-related protein requires both overlapping and distinct sequence motifs

EditorialMaterial (1)

Morphogens, new passengers on lipoprotein particles

Proyecto (28)

ApoER2/LRP8 trafficking and Reelin signaling alterations in rare neurological genetic diseases affecting secretory and endosomal pathways
LysosHead=> Lysosomes Signaling in Health and Disease􀀀
REELIN-INDUCED APOER2 RECEPTOR TRAFFICKING AND SIGNALING=> FUNCTIONAL CROSSTALK WITH ENDOSOMAL PROTEINS, ARF6 AND SNX27. IMPLICATIONS FOR CELL MIGRATION AND NEURONAL POLARITY
Millenium Nucleus in Regenerative Medicine (MINREB)
PARTICIPACION DE APOER2, SU LIGANDO REELINA Y LAS GTPASAS MONOMERICAS DE LA FAMILIA RHO EN LA MIGRACION DE LA CELULA DE SCHWANN=> IMPLICANCIAS EN REGENERACION AXONAL PERIFERICA.
Promoción Medio Externo (PME) asociado al MINREB
Millenium Nucleus in Regenerative Medicine (MINREB)
Novel aspects of apoER2 trafficking and function revealed by its interaction with the cytosolic adaptor proteins SNX17 and AP4
Role of the multivesicular body pathway and lysosomes in the turnover of the amyloid precursor protein; Implications foramyloid-beta generation and Alzheimer's Disease
Millenium Nucleus in Regenerative Medicine (MINREB)
Contribution of the endocitosis and the proteolytic processing to the neurotrophin signaling. Crosstalk with the apoER2/reelin system
Función y regulación de megalina en el epitelio de la vesícula biliar y su participación en la patogenia de la litiasis biliar de colesterol
Role of the nuclear factor PXR in gallstone disesase
ARCUS=> Etude d’une pathologie anormalement fréquente au Chili, la lithiase de la vésicule biliaire
FONDAP Center for Cell Regulation and Pathology
Apoptosis en la neurodegeneración=> Función de la quinasa c-abl y la proteína p73, posible efecto modulador del ApoER2
DMD fibrosis=> Role of CTGF, LRP and proteoglycans
Trafficking of LRP and megalin in polarized cells
FONDAP Center for Cell Regulation and Pathology
Megalina y ApoER2, receptores de la familia del LDL-R=> Modelos de estudio del tráfico intracelular en células polarizadas
Megalina y ApoER2, receptores de la familia del LDL-R=> Modelos de estudio del tráfico intracelular en células polarizadas
ESTUDIOS SOBRE LA INTERACCION ENTRE HFE, LA PROTEÍNA DE LA HEMACROMATOSIS HEREDITARIA Y DMT1, EL TRANSPORTADOR APICAL DE HIERRO, EN CELULAS DE EPITELIO INTESTINAL EN CULTIVO
DETERMINANTES MOLECULARES DE LA INTERACCION DE LOS RECEPTORES DE LA FAMILIA DEL LDL-R, LRP Y MEGALINA, CON EL AMBIENTE.
Estudio de los determinantes moleculares del tráfico intracelular de Megalina y LRP=> la destinación subcelular y rutas endocíticas determinan la función diferencial de los receptores
La glía en la generación y neurotoxicidad de los agregados de b-amiloide en la enfermedad de Alzheimer=> estudio y diseño de un posible instrumento diagnóstico de la población susceptible
ESTUDIO DE AUTOANTICUERPOS EN ENFERMEDADES AUTOINMUNES
MECANISMOS MOLECULARES DE LA BIOGENESIS Y REGULACION DE FUNCIONES DE LA SUPERFICIE CELULAR.
Mecanismos moleculares de la biogénesis y regulación de funciones de la superficie celular

Review (2)

The functions of Reelin in membrane trafficking and cytoskeletal dynamics: implications for neuronal migration, polarization and differentiation
Lipoprotein receptors and cholesterol in APP trafficking and proteolytic processing, implications for Alzheimer's disease
59
Maria Paz Marzolo

Profesor Titular

Departamento de Biología Celular y Molecular

PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE, FAC. CIENCIAS BIOLOGICAS, DEPTO. BIOLOGIA

Santiago, Chile

5
Nibaldo Inestrosa

Full Professor

PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE

Santiago, Chile

3
Felipe Court

Full Professor and Director

Center for Integrative Biology

Universidad Mayor

Huechuraba, Chile

3
Francisca Bronfman

Full Professor

Instituto de Ciencias Biomédicas

Universidad Andrés Bello

Santiago, Chile

2
Maria-Isabel Yuseff

Associate Professor

Cellular and Molecular Biology

Pontificia Universidad Católica de Chile

Santiago, Chile

2
Claudio Cabello

Full Professor

Ciencias Biologicas

UNIVERSIDAD ANDRES BELLO

Santiago, Chile

2
Jose Parraguez

Investigador

Particular

Santiago, Chile

2
Marco Nuñez

Professor

Biology

Fac. Ciencias, Universidad de Chile

Santiago, Chile

2
Luis González

Full Professor

School of Medicine

Universidad San Sebastián

Santiago, Chile

2
Rodrigo Fuentealba

Postdoctoral Research Associate

Departamento de Inmunología Clínica y Reumatología / Facultad de Medicina

Pontificia Universidad Católica

Santiago, Chile

1
Fernando Ezquer

Full Professor

Center for Regenerative Medicine

Universidad del Desarrollo

Santiago, Chile

1
Benjamín Erranz

Investigador-Docente

Instituto de Ciencias e Innovación en Medicina

Universidad del Desarrollo

Santiago, Chile

1
Pabla Aguirre

Asistente de investigación

Biología

Universidad de Chile

Santiago, Chile

1
Alejandro Rojas

Assistant Professor

UNIVERSIDAD AUSTRAL DE CHILE

Valdivia, Chile

1
Brigitte van Zundert

Full Professor

UNIVERSIDAD ANDRÉS BELLO, CENTRO DE INVESTIGACIONES BIOMÉDICAS

Santiago, Chile

1
Andrés Couve

Profesor Titular

Neurociencia

FACULTAD DE MEDICINA, UNIVERSIDAD DE CHILE

Santiago, Chile

1
ignacio jausoro

POSTDOC

BIOLOGIA CELULAR Y MOLECULAR

PONTIFICIA UNIVERSIDAD DE CHILE

SANTIAGO, Chile

1
Maria Barria

Assistant Professor

Departamento de Microbiologia

Universidad de Concepción

CONCEPCION, Chile

1
Ricardo Matute

Associate Professor

Centro Integrativo de Biología y Química Aplicada (CIBQA)

Universidad Bernardo O'Higgins

Santiago , Chile

1
Steffen Härtel

Full Professor

Instituto de Ciencias Biomédicas

University of Chile

Santiago, Chile

1
Carlos Cespedes

Tecnologo Medico

Fisiologia

P. Universidad Católica de Chile

Santiago, Chile

1
Carlos Vio

Profesor

Fisiologia

PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE

Santiago, Chile

1
Juan Miquel

Full Professor

Gastroenterology

PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE

Santiago, Chile

1
Jorge Cancino

Assistant Professor

Centro de Biología Celular y Biomedicina

Universidad San Sebastián

Santiago, Chile

1
Enrique Brandan

Profesor Titular

Biología Celular y Molecular

PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE

Santiago, Chile

1
Rommy von Bernhardi

Full Professor

Neurology

DEPT. NEUROLOGY, FAC. MEDICINE PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE

Santiago, Chile