Ute Woehlbier

Director of the center and Associate Professor


In In 2003 she obtained a Dipl. Biol./M.Sc. in Molecular Biology and in 2007 a Dr. rer. nat./Ph.D. both from the University of Heidelberg, Germany. During her master's and doctorate, she studied the macromolecular structure and immunogenicity of the surface proteins of the malaria parasite Plasmodium falciparum with the aim of contributing to the development of the malaria vaccine. Between 2007 and 2010, she was a postdoc in the Center for Biological Complexity at Virginia Commonwealth University, USA, studying the vaccine potential of proteins from the intestinal parasite Cryptosporidium sp. identified by a reverse vaccinology approach using genome sequencing and bioinformatics. Between 2010-2013 she completed a second Postdoc in at the University of Chile, Chile, in Neuroscience, studying the role of mutations in protein disulfide isomerases identified in patients with amyotrophic lateral sclerosis (ALS). In October 2013, she established her laboratory at the Universidad Mayor characterizing new proteins in the disease. Currently her team is focusing on studying new proteins involved in ALS identified by a web-based bioinformatics approach. It uses a wide spectrum of techniques, such as bioinformatics, molecular biology, biochemistry, cell biology, as well as in vivo model systems to understand the role of in most cases uncharacterized or understudied proteins in disease.



Ute Woehlbier

PUBLICATIONS

2015-pres

Oyarce-Pezoa S, Rucatti GG, Muñoz-Carvajal F, Sanhueza N, Gomez W, Espinoza S, Leiva M, García N, Ponce DP, SanMartín CD, Rojas-Rivera D, Salvadores N, Behrens MI, Woehlbier U, Calegaro-Nassif M, Sanhueza M. The autophagy protein Def8 is altered in Alzheimer's disease and Aβ42-expressing Drosophila brains. Sci Rep. 2023 Oct 10;13(1):17137. doi: 10.1038/s41598-023-44203-6.

Sanhueza SA, Vidal MA, Hernández MA, Henriquez-Beltran ME, Cabrera CD, Quiroga RA, Antilef BE, Aguilar KP, Castillo DA, Llerena FJ, Fraga MA, Nazal M, Castro E, Lagos P, Moreno A, Lastra JJ, Gajardo J, Garces P, Riffo B, Buchert J, Sanhueza R, Ormazabal VA, Saldivia P, Vargas C, Nourdin G, Koch E, Zúniga FE, Lamperti LI, Bustos P, Guzman-Gutiérrez E, Aguayo C, Ferrada L, Cerda F, Woehlbier U, Riquelme E, Yuseff MI, Muñoz B, Lombardi G, de Gonzalo-Calvo D, Salomon C, Verdugo RA, Quiñones L, Colombo A, Labarca G, Nova-Lamperti E. Cardiac dysfunction mediators supports long-term pulmonary dysfunction in Long-COVID19 patients. Front Med (Lausanne). 2023 Oct 6;10:1271863. doi: 10.3389/fmed.2023.1271863. eCollection 2023.

Bergmann CA, Beltran S, Vega-Letter AM, Murgas P, Hernandez MF, Gomez L, Labrador L, Cortés BI, Poblete C, Quijada C, Carrion F, Woehlbier U*, Manque PA*. (2022) The Autophagy Protein Pacer Positively Regulates the Therapeutic Potential of Mesenchymal Stem Cells in a Mouse Model of DSS-Induced Colitis. Cells. 2022 Apr 30;11(9):1503. (*equal contribution)

Espinoza S, Grunenwald F, Gomez W, García F, Abarzúa-Catalan L, Oyarce-Pezoa S, Hernandez MF, Cortés BI, Uhrig M, Ponce DP, Durán-Aniotz C, Hetz C, SanMartín CD, Cornejo VH, Ezquer F, Parra V, Behrens MI, Manque PA, Rojas-Rivera D, Vidal RL, Woehlbier U, Nassif M. (2022) Neuronal Rubicon Represses Extracellular APP/Amyloid β Deposition in Alzheimer's Disease. Cells. 2022 Jun 7;11(12):1860.

Medinas D, Malik S, Yıldız-Bölükbaşı E, Borgonovo J, Saaranen MJ, Urra H, Pulgar E, Afzal M, Contreras D, Wright MT, Bodaleo F, Quiroz G, Rozas P, Mumtaz S, Díaz R, Rozas C, Cabral-Miranda F, Piña R, Valenzuela V, Uyan O, Reardon C, Woehlbier U, Brown RH, Sena-Esteves M, Gonzalez-Billault C, Morales B, Plate L, Ruddock LW, Concha ML, Hetz C, Tolun A. Mutation in protein disulfide isomerase A3 causes
neurodevelopmental defects by disturbing endoplasmic reticulum proteostasis. EMBO J. 2022 Jan 17;41(2):e105531.

Leyton E, Matus D, Espinoza S, Benitez JM, Cortés BI, Gomez W, Arévalo NB, Murgas P, Manque P, Woehlbier U, Duran-Aniotz C, Hetz C, Behrens MI, SanMartín CD, Nassif M. DEF8 and Autophagy-Associated Genes Are Altered in Mild Cognitive Impairment, Probable Alzheimer's Disease Patients, and a Transgenic Model of the Disease. J Alzheimers Dis. 2021;82(s1):S163-S178

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.



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.

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

Active

2024-2028 FONDECYT Regular 1240176 (Investigador Principal)

Completed

2020-2024 FONDECYT Regular 1200459 (Investigador Principal)

2019-2020 FONDO Puente PEP I-2019054 (Investigador Principal)

2015-2019 FONDECYT Regular 1150743 (Investigador Principal)

2010-2013 Fondecyt Postdoc 3110067 (Investigador Principal)

TEAM

Giselle Espinosa PhD student of Integrative Genomics, Universidad Mayor

Carla Alarcon PhD student of Neurobiology, Universidad Mayor

Leonardo Rodriguez PhD student of Integrative Genomics, Universidad Mayor


Former Lab Members

Sebastian Beltran PhD student of Integrative Genomics, Universidad Mayor and Postdoc, now Director of the Medical Technology School, Universidad Mayor, Chile

Luis Labrador PhD student of Integrative Genomics, now Postdoc in Cincinnati Children's Hospital, USA

Emiliano Vicencio PhD student of Integrative Genomics, now Postdoc at University of Chile, Chile

NETWORK

National

Mauricio Hernandez, Melisa Institute, Concepcion, Chile

Estefania Nova-Lamberti, Universidad de Concepcion, Chile

Diego Rojas-Rivera, Center for Biomedicine, Universidad Mayor, Chile

Melissa Nassif, Center for Biomedicine, Universidad Mayor, Chile

Rene Vidal, Center for Integrative Biology, Universidad Mayor, Chile

Francisca Cornejo, Center for Integrative Biology, Universidad Mayor, Chile

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

Cesar Cardenas, Center for Integrative Biology, Universidad Mayor, Chile

International

Danilo Medinas, University of Sao Paolo, Brasil

Mathieu Bertrand, Inflammation Research Center, Ghent University, Belgium