Ute Woehlbier

Profesor Asociado


Obtuvo en 2003 un Dipl. Biol./M.Sc. En biología molecular y en 2007 un Dr. rer. nat./Ph.D. Ambos de la Universidad de Heidelberg, Alemania. Durante su maestría y doctorado, tanto en la investigación realizada en el laboratorio del Prof. Dr. Hermann Bujard, estudió la estructura macromolecular y la inmunogenicidad de las proteínas de la superficie del parásito de la malaria Plasmodium falciparum con el objetivo de contribuir al desarrollo de la vacuna contra la malaria. Entre 2007 y 2010, realizó un postdoctorado en el laboratorio del Prof. Dr. Gregory Buck en la Virginia Commonwealth University, EE. UU., Estudiando el potencial de la vacuna de las proteínas del parásito intestinal Cryptosporidium sp. identificado por un enfoque de vacunología inversa utilizando la secuencia del genoma y la bioinformática. Entre 2010-2013 realizó un segundo Postdoc en el laboratorio del Prof. Claudio Hetz en la Universidad de Chile, Chile, en neurociencia, estudiando el papel de las mutaciones en las proteínas disulfuro isomerasas identificadas en pacientes con esclerosis lateral amiotrófica (ELA). En octubre de 2013, estableció su laboratorio en la Universidad Mayor caracterizando nuevas proteínas en la enfermedad. Actualmente su equipo esta enfocando en estudiar nuevas proteínas involucradas en la ELA identificadas por un enfoque bioinformático basado en la red. Utiliza un amplio espectro de técnicas, como bioinformática, biología molecular, bioquímica, biología celular, así como sistemas de modelos in vivo para comprender el papel de estas en la mayoría de los casos de proteínas no caracterizadas o no estudiadas en la enfermedad.


Ute Woehlbier

PUBLICATIONS

Beltran S., M. Nassif, E. Vicencio, J. Arcos, L. Labrador, B.I. Cortes, C. Cortez, C.A. Bergmann, S. Espinoza, M.F. Hernandez, J.M. Matamala, L. Bargsted, S. Matus, D. Rojas-Rivera, M.J.M. Bertrand, D.B. Medinas, C. Hetz, P.A. Manque, U. Woehlbier. 2019. Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis. Mol Neurodegener. 2019 Mar 27;14(1):14. doi: 10.1186/s13024-019-0313-9.

Medinas, D.B., P. Rozas, F. Martínez Traub, U. Woehlbier, R.H. Brown, D.A. Bosco, and C. Hetz. 2018. Endoplasmic reticulum stress leads to accumulation of wild-type SOD1 aggregates associated with sporadic amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 115. doi: 10.1073/pnas.1801109115.

Yıldırım, Y., T. Ouriachi, U. Woehlbier, W. Ouahioune, M. Balkan, S. Malik, and A. Tolun. 2018. Linked homozygous BMPR1B and PDHA2 variants in a consanguineous family with complex digit malformation and male infertility. Eur. J. Hum. Genet. 26. doi:10.1038/s41431-018-0121-7.

Yildiz Bölükbasi, L.E., S. Mumtaz, M. Afzal, U. Woehlbier, S. Malik, and A. Tolun. 2018. Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly. J. Med. Genet. 55. doi:10.1136/jmedgenet-2017-104758.

Nassif, M., U. Woehlbier, and P.A. Manque. 2018. The Delicate Balance of Autophagy in Neurodegeneration, Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Pages 387-399.

Nassif, M., U. Woehlbier, and P.A. Manque. 2017. The Enigmatic Role of C9ORF72 in Autophagy, Front Neurosci. 11. doi:10.3389/fnins.2017.00442.

Woehlbier, U., A. Colombo, M.J. Saaranen, V. Pérez, J. Ojeda, F.J. Bustos, C.I. Andreu, M. Torres, V. Valenzuela, D.B. Medinas, P. Rozas, R.L. Vidal, R. Lopez-Gonzalez, J. Salameh, S. Fernandez-Collemann, N. Muñoz, S. Matus, R. Armisen, A. Sagredo, K. Palma, T. Irrazabal, S. Almeida, P. Gonzalez-Perez, M. Campero, F.-B. Gao, P. Henny, B. Van Zundert, L.W. Ruddock, M.L. Concha, J.P. Henriquez, R.H. Brown, and C. Hetz. 2016. ALS-linked protein disulfide isomerase variants cause motor dysfunction. EMBO J. 35. doi:10.15252/embj.201592224.

Castillo, V., M. Oñate, U. Woehlbier, P. Rozas, C. Andreu, D. Medinas, P. Valdés, F. Osorio, G. Mercado, R.L. Vidal, B. Kerr, F.A. Court, and C. Hetz. 2015. Functional role of the disulfide isomerase ERp57 in axonal regeneration. PLoS One. 10. doi:10.1371/journal.pone.0136620.

Torres, M., D.B. Medinas, J.M. Matamala, U. Woehlbier, V.H. Cornejo, T. Solda, C. Andreu, P. Rozas, S. Matus, N. Muñoz, C. Vergara, L. Cartier, C. Soto, M. Molinari, and C. Hetz. 2015. The protein-disulfide isomerase ERp57 regulates the steady-state levels of the prion protein. J. Biol. Chem. 290. doi:10.1074/jbc.M114.635565.

Gonzalez-Perez, P., U. Woehlbier, R.-J. Chian, P. Sapp, G.A. Rouleau, C.S. Leblond, H. Daoud, P.A. Dion, J.E. Landers, C. Hetz, and R.H. Brown. 2015. Identification of rare protein disulfide isomerase gene variants in amyotrophic lateral sclerosis patients. Gene. 566. doi:10.1016/j.gene.2015.04.035.

Roche, J.K., A.L. Rojo, L.B. Costa, R. Smeltz, P. Manque, U. Woehlbier, L. Bartelt, J. Galen, G. Buck, and R.L. Guerrant. 2013. Intranasal vaccination in mice with an attenuated Salmonella enterica Serovar 908htr A expressing Cp15 of Cryptosporidium: impact of malnutrition with preservation of cytokine secretion, Vaccine 31. doi: 10.1016/j.vaccine.2012.12.007.

Andreu, C.I., U. Woehlbier, M. Torres, and C. Hetz. 2012. Protein disulfide isomerases in neurodegeneration: From disease mechanisms to biomedical applications. FEBS Lett. 586. doi:10.1016/j.febslet.2012.07.023.

Torres, M., L. Cartier, J.M. Matamala, N. Hernández, U. Woehlbier, and C. Hetz. 2012. Altered prion protein expression pattern in CSF as a biomarker for Creutzfeldt-jakob disease. PLoS One. 7. doi:10.1371/journal.pone.0036159.

Manque, P.A., U. Woehlbier, A.M. Lara, F. Tenjo, J.M. Alves, and G.A. Buck. 2012. Identification and characterization of a novel calcium-activated apyrase from Cryptosporidium parasites and its potential role in pathogenesis. PLoS One. 7. doi: 10.1371/journal.pone.0031030.

Woehlbier, U., and C. Hetz. 2011. Modulating stress responses by the UPRosome: A matter of life and death. Trends Biochem. Sci. 36. doi:10.1016/j.tibs.2011.03.001.

Manque, P., and U. Woehlbier. 2011. Systems Biology-Based Approaches Applied to Vaccine Development, Handbook of Research on Computational and Systems Biology: Interdisciplinary Applications, USA, IGI Global, Pages 61-78.

Manque, P.A., F. Tenjo, U. Woehlbier, A.M. Lara, M.G. Serrano, P. Xu, J.M. Alves, R.B. Smeltz, D.H. Conrad, and G.A. Buck. 2011. Identification and immunological characterization of three potential vaccinogens against Cryptosporidium species, Clin Vaccine Immunol. 18.

Woehlbier, U., C. Epp, F. Hackett, M.J. Blackman, and H. Bujard. 2010. Antibodies against multiple merozoite surface antigens of the human malaria parasite Plasmodium falciparum inhibit parasite maturation and red blood cell invasion. Malar. J. 9. doi:10.1186/1475-2875-9-77.

Koussis, K., C. Withers-Martinez, S. Yeoh, M. Child, F. Hackett, E. Knuepfer, L. Juliano, U. Woehlbier, H. Bujard, and M.J. Blackman. 2009. A multifunctional serine protease primes the malaria parasite for red blood cell invasion. EMBO J. 28. doi:10.1038/emboj.2009.22.

Lucchi, N.W., J.E. Tongren, V. Jain, A.C. Nagpal, C.W. Kauth, U. Woehlbier, H. Bujard, A.P. Dash, N. Singh, J.K. Stiles, and V. Udhayakumar. 2008. Antibody responses to the merozoite surface protein-1 complex in cerebral malaria patients in India. Malar. J. 7. doi:10.1186/1475-2875-7-121.

Kauth, C.W., U. Woehlbier, M. Kern, Z. Mekonnen, R. Lutz, N. Mücke, J. Langowski, and H. Bujard. 2006. Interactions between merozoite surface proteins 1, 6, and 7 of the malaria parasite Plasmodium falciparum. J. Biol. Chem. 281. doi:10.1074/jbc.M604641200.

Woehlbier, U., C. Epp, C.W. Kauth, R. Lutz, C.A. Long, B. Coulibaly, B. Kouyaté, M. Arevalo-Herrera, S. Herrera, and H. Bujard. 2006. Analysis of antibodies directed against merozoite surface protein 1 of the human malaria parasite Plasmodium falciparum. Infect. Immun. 74. doi:10.1128/IAI.74.2.1313-1322.2006.

RESEARCH LINES

Bioinformatic identification and characterization of novel proteins involved in disease.

Jointly with the lab of Dr. Patricio Manque, our lab combines systems biology with molecular biology, biochemistry, cellular and animal studies to understand mechanisms of human disease. We apply network-based approaches to build disease-specific networks allowing us to identify new genes, pathways, subnetworks responsible for the molecular pathology of a disease. To achieve this, we collect large data sets (RNAseq, CNV, HUGE, Proteomics) and combine them with a diverse set of bioinformatic tools, e.g. convergent analysis. This approach permits us, (i) to identify topological changes in the overall structure of the network, (ii) to unravel new genes or new interactions associated with a disease, and (iii) to detect potential master regulators in the disease specific networks. Once we bioinformatically identified a candidate gene we investigate its role during disease with a broad set of experimental tools. Currently we are focusing on the characterization of novel genes inserted in the diseasosome of the neurodegenerative disease amyotrophic lateral sclerosis (ALS).

The role of the novel autophagy protein Pacer in ALS pathology.

A bioinformatic network-based approach suggested the previously uncharacterized protein Pacer to have a role in ALS pathology through its function in autophagy. Using cellular and mouse models of ALS we are now investigating the role of Pacer during disease and whether or not its loss or gain of function has any effect on molecular mechanisms of neurodegeneration.

The role of the stress granule associated protein FAM120A in ALS pathology.

By tailoring our bioinformatic approach specifically towards identifying novel proteins involved in RNA metabolism, a major pathway affected in ALS, we found the protein FAM120A to be embedded in the ALS disease network, due to interactions with several known causal ALS genes. Using cellular approaches, we are investigating how FAM120A could be involved in generating pathological features of ALS.

Cellular mechanisms of the immune modulatory potential of Mesenchymal stem cells.

Mesenchymal stem cells offer an important and widely used cellular therapy approach for different diseases, e.g. inflammatory bowel syndrome, Crohn’s disease, as well as nervous system diseases, such as ALS. Autophagy has been suggested to be involved in the immune modulatory potential of Mesenchymal stem cells (MSCs), which are now widely used as a cellular therapy approach. Hence, together with the lab of Dr. Manque we investigated if the novel autophagy protein Pacer performs a regulatory function towards this property of MSCs.

PROJECTS

Name: Fondo Puente

Type of Project: National Internal Competitive Fund.

Sponsor institution: Umayor

Responsible investigator: Ute Woehlbier

Date of execution: 2019-2020

Name: UMayor Postodoctoral

Type of Project: National Internal Competitive Fund.

Funding institution: Umayor

Responsible investigator: Sebastian Beltrán

Other Investigators: Sponsor Ute Woehlbier

Date of execution 2018-2020

Name: FONDECYT

Type of Project: National External Competitive Fund.

Funding institution: CONICYT

Responsible investigator: Ute Woehlbier

Date of execution: 2015-2019

TEAM

Leonardo Rodriguez

Research Assistant

Bachelor in Biotechnology Engineering from Universidad Andres Bello, Santiago, Chile.

Leonardo oversees all animal work of the lab, focusing on the phenotypic characterization of novel animal models.

Sebastian Beltran

Postdoctoral Research Fellow

Bachelor in Medical Technology and Ph.D. in Integrative Genomics both from Universidad Mayor, Santiago, Chile.

Sebastian is studying the relationship of autophagy with the process of cell death in neurons.

Emiliano Vicencio

Ph.D. student Integrative Genomics Program

Bachelor in Biotechnology from Universidad Mayor, Santiago, Chile.

Emiliano is performing his Ph.D. thesis in the lab. He is studying the putative role of FAM120A in pathologic mechanisms of ALS.

Luis Labrador

Ph.D. student Integrative Genomics Program

Bachelor in Biology from Universidad de Los Andes, Venezuela.

Luis is performing his Ph.D. thesis in the lab. He is studying the molecular and cellular functions of Pacer in motoneurons during ALS pathogenesis in in vitro and in vivo models.

NETWORK

National

Claudio Hetz, Biomedical Neuroscience Institute, Universidad de Chile, Santiago, Chile

Danilo Medinas, Biomedical Neuroscience Institute, Universidad de Chile, Santiago, Chile

Bredford Kerr, Centro de Estudios Científicos, Valdivia, Chile

Soledad Matus, Fundacion Ciencia Vida, Santiago, Chile

Cristian Cortez, Center for Genomics and Bioinformatics, Universidad Mayor, Santiago, Chile

Melissa Nassif, Center for Integrative Biology, Universidad Mayor, Santiago, Chile

Felipe Court, Center for Integrative Biology, Universidad Mayor, Santiago, Chile

Leonardo Valdivia, Center for Integrative Biology, Universidad Mayor, Santiago, Chile

International

Aslihan Tolun, Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey

Mathieu Bertrand, Inflammation Research Center, Ghent University, Ghent, Belgium

Thomas Wishart, The Roslin Institute, University of Edinburgh, Edinburgh, Scotland