Researh & development

Cancer Cell Biology Lab

Profile

Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián

The tumor microenvironment (TME) is composing by different type of cells such as tumor, endothelial, and immune cells, among others. These cells have the capability to interact between each other’s and promote different pro-tumorigenic properties like chemoresistance angiogenesis and metastasis for example. One way of cellular communication are the extracellular vesicles (EVs), small message with proteins, RNAs, and lipids as a content, which can transfer this information from one cell to another cell to change its function. Our lab is currently studying how different stimulus (cytokines, chemotherapy or hypoxia) can regulate the biogenesis and secretion of EVs produced by tumor cells, and how these EVs can modulate the TME to promote the tumor progression.

 

  • Research Head: Manuel Varas-Godoy
  • Doctoral Students: Albano Cáceres-Verschae, Jorge Catalan, Álvaro Neira, Belén Gaete-Ramírez
  • Master Students: Javiera Portus
  • Post-doctoral Fellows: Francisca Álvarez-Astudillo

  • Cristóbal Cerda-Troncoso (Former Ph.D. student, 2019-2022)
  • Gonzalo Gomara (Former Master student, 2018)
  • Paula Valenzuela (Former Master student, 2016)
  • Jonathan Lillo (Former Undergraduate student, 2022)
  • Liseth Orosco (Former Undergraduate student, 2022)
  • Javiera Portus (Former Undergraduate student, 2021)
  • Daniela Riveros (Former Undergraduate student, 2020)
  • Nelly Vera (Former Undergraduate student, 2020)
  • Felipe Grünenwald (Former Undergraduate student, 2020)
  • Sebastian Venegas (Former Undergraduate student ,2017)
  • Evelyn Zirotti (Former Undergraduate student, 2017)
  • Constanza Pinochet (Former Undergraduate student, 2013).

 

National Collaborations:

  • Dr. Andrew Quest (University of Chile)
  • Dr. Vicente Torres (University of Chile)
  • Dra. Veronica Palma (University of Chile)
  • Dr. Julio Tapia (University of Chile)
  • Dra. Fabiola Sanchez (Austral University of Chile)
  • Dra. Claudia Quezada (Austral University of Chile)
  • Dra. Pamela Leal (Univerity of La Frontera)
  • Dra. Patricia Burgos (San Sebastian University)
  • Dr. Alejandro Godoy (San Sebastian University)
  • Dr. Rodrigo Acuña (University of Desarrollo)

Internationals Collaborations:

  • Dr. Per Úhlen (Karolinska Institutet, Suecia)
  • Dr. Matias Ostrowski (University of Buenos Aires, Argentina)

Publications

Bhandage AK, Olivera GC, Kanatani S, Thompson E, Loré K, Varas-Godoy M, Barragan A.“A motogenic GABAergic system of mononuclear phagocytes facilitates dissemination of coccidian parasites”. eLife (2020)

Ocaranza MP, Godoy I, Jalil JE, Varas M, Collantes P, Pinto M, Román M, Ramírez C, Copaja M, Diaz-Araya G, Castro P, Lavandero S. “Enalapril attenuates downregulation of angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat”. Hypertension (2006)

Ocaranza MP, Lavandero S, Jalil JE, Moya J, Pinto M, Novoa U, Apablaza F, Gonzalez L, Hernandez C, Varas M, Lopez R, Godoy I, Verdejo H, Chiong M. “Angiotensin-(1-9) regulates cardiac hypertrophy in vivo and in vitro” . J Hypertension (2010)

Villota C, Campos A, Vidaurre S, Oliveira-Cruz L, Boccardo E, Burzio VA, Varas M, Villegas J, Villa LL, Valenzuela PD, Socias M, Roberts S, Burzio LO.“Expression of mitochondrial ncRNAs is modulated by high risk HPV oncogenes”. J Biol Chem. (2012)

Sandoval M, Luarte A, Herrera-Molina R, Varas-Godoy M, Santibañez M, Rubio FJ, Smit AB, Gundelfinger ED, Li KW, Smalla KH, Wyneken U.“The glycolytic enzyme Aldolase C is up-regulated in rat forebrain microsomes and in the cerebrospinal fluid after repetitive fluoxetine treatment”. Brain Research (2013)

Ibarra C, Vicencio JM, Varas-Godoy M, Jaimovich E, Rothermel BA, Uhlén P, Hill JA, Lavandero S.“An integrated mechanism of cardiomyocyte nuclear Ca2+ signaling”. J Mol Cell Cardiol. (2014)

Bulatovic I, Ibarra C, Österholm C, Wang H, Beltrán-Rodríguez A, Varas-Godoy M, Månsson-Broberg A, Uhlén P, Simon A, Grinnemo KH. “Sublethal Caspase Activation Promotes Generation of Cardiomyocytes from Embryonic Stem Cells”. PloS One (2015)

Ampuero E, Luarte A, Santibañez M, Varas-Godoy M, Toledo J, Diaz-Veliz G, Cavada G, Rubio FJ, Wyneken U. “Twochronic stress models based on movement restriction in rats respond selectively to antidepressant drugs: Aldolase C as a potential biomarker”. Int J Neuropsychopharmacology (2015)

Alfaro IE, Varela-Nallar L, Varas-Godoy M, Inestrosa NC. “The Ror2 tyrosine kinase receptor regulates dendritic spine morphogenesis in hippocampal neurons”. Mol Cell Neurosci. (2015)

Parodi J, Montecinos-Oliva C, Varas R, Alfaro IE, Serrano FG, Varas-Godoy M, Muñoz FJ, Cerpa W, Godoy JA, Inestrosa NC.“Wnt-5a inhibits K+ currents in hippocampal synapses through nitric oxide production”. Mol Cell Neurosci. (2015)

Perez-Sepulveda A, Monteiro LJ, Dobierzewska A, España-Perrot PP, Guzmán-Rojas AM, González MI, Palominos-Rivera M, Irarrazaval CE, Figueroa-Diesel H, Varas-Godoy M, Illanes SE. “Placental Aromatase is Deficient in Placental Ischemia and Preeclampsia”. PloS One (2015)

Niechi I, Silva-Pavez E, Cabello P, Huert H, Carrasco V, Villar P, Cataldo LR, Marcelain K, Armisen R, Varas-Godoy M, Fernandez C, Tapia JC. “Colon cancer cell invasion is promoted by CK2 through increase of ECE-1c protein stability”. Oncotarget (2015)

Mardones MD, Andaur GA, Varas-Godoy M, Henriquez JF, Salech F, Behrens MI, Couve A, Inestrosa NC, and Varela-Nallar L. “Frizzled-1 receptor regulates adult hippocampal neurogenesis”. Molecular Brain (2016)

Chaparro A, Gaedechens D, Ramírez V, Zuñiga E, Kusanovic JP, Inostroza C, Varas-Godoy M, Silva K, Salomon C, Rice G, Illanes SE. “Placental Biomarkers and Angiogenic Factors in Oral Fluids of Patients with Preeclampsia”. Prenatal Diagnosis (2016)

Weidner JM, Kanatani S, Uchtenhangen H, Varas-Godoy M, Schulte T, Engelberg K, Gubbels MJ, Sun HS, Harrison R, Achour A, Barragan A.“Migratory activation of parasitized dendritic cells by the protozoan Toxoplasma gondii 14-3-3 protein”. Cellular Microbiology (2016)

Alcayaga-Miranda F, Varas-Godoy M, Khoury M. “Harnessing the angiogenic potential of stem cell-derived exosomes for vascular regeneration”. Stem Cells International. (2016)

Palmer KR, Kautu´u-Lino TJ, Cannon P, De Silva MS, Varas-Godoy M, Acuña S, Galaz J, Tong S, and Illanes SE. ”Maternal plasma concentrations of the placental specific sFLT-1 variant, sFLT-1 e15a, in fetal growth restriction and preeclampsia”. JMFNM (2017)

Alarcón V, Hernández S, Rubio L, Alvarez F, Flores Y, Varas-Godoy M, De Ferrari G, Kann M, Villanueva RA, and Loyola A. “The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state”. Scientific Reports (2016)

Alcayaga-Miranda F, González PL, López-Verrilli A, Varas-Godoy M, Aguila-Díaz C, Contreras L and Khoury M. “Prostate tumor-induced angiogenesis is blocked by exosomes derived from menstrual stem cells through the inhibition of reactive oxygen species”. Oncotarget (2016)

Lobos-González L, Silva V, Araya M, Restovic F, Echenique J, Oliveira-Cruz L, Fitzpatrick C, Briones M, Villegas J, Villota C, Vidaurre S, Borgna V, Socias M, Valenzuela S, Lopez C, Socias T, Varas M, Díaz J, Burzio LO and Burzio VA. “Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors”. Oncotarget (2016)

Campos-Acuña J, Varas-Godoy M, Haidar ZS. “Physicochemical characterization of chitosan-hyaluronan-coated solid lipid nanoparticles for the targeted delivery of paclitaxel: a proof-of-concept study in breast cancer cells”. Nanomedicine (2017)

Caviedes A, Varas-Godoy M, Lafourcade C, Sandoval S, Bravo-Alegria J, Kaehne T, Massmann A, Figueroa JP, Nuluart F, Wyneken U.“Endothelial nitric oxide synthase is present in dendritic spines of neurons in primary cultures”. Frontiers in Cellular Neuroscience (2017)

Gálvez-Cancino F, Roco J, Rojas-Colonelli N, Flores C, Murgas P, Cruz-Gómez S, Oyarce C, Varas-Godoy M, Sauma D, Lladser A. “A short hairpin RNA-based adjuvant targeting NF-κB repressor IκBα promotes migration of dendritic cells to draining lymph nodes and antitumor CTL responses induced by DNA vaccination”. Vaccine (2017)

Varas-Godoy M†, Rice G, Illanes SE. “The cross talk between ovarian cancer stem cells niche and the tumor microenvironment”. Stem Cells International (2017)

Varas-Godoy M, Lladser A, Farfan N, Villota C, Villegas J, Tapia JC, Burzio LO, Burzio VA, Valenzuela PDT.“In vivo knockdown of antisense noncoding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization”. Pigment Cell & Melanoma Research (2018)

Ólafsson EB, Varas-Godoy M, Barragan A. “Toxoplasma gondii infection shifts dendritic cells into an amoeboid rapid migration mode encompassing podosome dissolution, secretion of TIMP-1 and reduced proteolysis of extracellular matrix”. Cellular Microbiology (2018)

Kanatani S, Fuks JM, Ólafsson EB, Westermark L, Chambers B, Varas-Godoy M, Uhlén P, Barragan A. “Voltage-dependent calcium channel signaling mediates GABAA receptor-induced migratory activation of dendritic cells infected by Toxoplasma gondii”. Plos Pathogens (2017)

Palmeiro YK, Orellana P, Venegas P, Monteiro LJ, Varas-Godoy M, Norwitz E, Rice G, Osorio E, Illanes SE. “Effects of earthquake on perinatal outcomes: A Chilean register-based study”. PloS One (2018)

Galvez-Cancino F, Lopez E, Menares E, Díaz X, Flores C, Caceres P, Hidalgo S, Chovar O, Alcantara-Hernandez M, Borgna V, Varas-Godoy M, Salazar-Onfray F, Idoyaga J, Lladser A.“Vaccination-induced skin-resident memory CD8+ T cells mediate strong protection against cutaneous melanoma”. Oncoimmunology (2018)

Chaparro A, Zuñiga E, Varas-Godoy M, Albers D, Ramirez V, Hernández M, Kusanovic JP, Acuña S, Rice G, Illanes S. “Periodontitis and placental growth factor in oral fluids are early pregnancy predictors of gestational diabetes mellitus”. Journal of Periodontology (2018)

Campos A, Salomon C, Bustos R, Diaz J, Martinez S, Silva V, Reyes C, Diaz Valdivia N, Varas-Godoy M, Lobos-Gonzalez L, Quest A. “Caveolin-1-containing extracellular vesicles transport adhesion proteins and promote malignancy in breast cancer”. Nanomedicine (2018)

Villota C*, Varas-Godoy M*, Jeldes E*, Campos A, Villegas J, Borgna V, Burzio L, Burzio V. “HPV-18 E2 protein downregulates antisense noncoding mitochondrial RNA-2, delaying replicative senescence of human keratinocytes”. Aging (2018)

Monteiro LJ, Cubillos S, Sanchez M, Acuña-Gallardo S, Venegas P, Herrera V, Lam EW, Varas-Godoy M, Illanes SE. “Reduced FOXM1 expressions limits trophoblast migration and angiogenesis and is associated with preeclampsia”. Reproductive Sciences (2019)

Ibarra C, Karlsson M, Codeluppi S, Varas-Godoy M, Zhang S, Mangsbo S, Hosseini A, Soltani N, Kaba R, Lundgren TK, Hosseini A, Tanaka N, Oya M, Wiklund P, Miyakawa A†, Uhlén P†.“BCG-Induced Cytokine Release in Bladder Cancer Cells is Regulated by Ca2+ Signaling”. Molecular Oncology (2019)

Gomez-Molina C, Sandoval M, Henzi R, Ramirez JP, Varas-Godoy M, Luarte A, Lafourcade CA, Lopez-Verrilli A, Smalla KH, Kaehne T, Wyneken U. “Small extracellular vesicles in rat serum contain astrocyte derived protein biomarkers of repetitive stress”. Int J Neuropsychopharmacology (2019)

Varas-Godoy M*, Acuña-Gallardo S*, Venegas-Duarte S, Hill C, Caceres-Verschae A, Realini O, Monteiro LJ, Zavala G, Khoury M, Romero R, Rice G, Illanes SE.“Angiogenic properties of menstrual stem cells are impaired in women with a history of preeclampsia”. Stem Cells International (2019)

Silva E, Villar P, Niechi I, Trigo C, Caamaño E, Muñoz JP, Fernández C, Aguayo F, Burzio VA, Varas-Godoy M, Castro AF, López de Armentia MM, Colombo MI, Tapia JC. “CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells”. Cell Death & Disease (2019)

Olafsson EB, Ross EC, Varas-Godoy M, Barragan A.“TIMP-1 promotes hypermigration of Toxoplasma-infected primary dendritic cells via CD63 / ITGB1 / FAK signaling”. Journal of Cell Science (2019)

Falcão A, Meijer M, Scaglione A, Rinwa P, Agirre E, Liang J, Larsen S, Heskol A, Frawley R, Klingener M, Varas-Godoy M, Raposo A, Ernfors P, Castro D, Nielsen M, Casaccia P, Castelo-Branco C. “PADI2-mediated citrullination is required for efficient oligodendrocyte differentiation and myelination”. Cell Reports (2019)

Monteiro LJ*, Varas-Godoy M*, Monckeberg M, Realini O, Hernández M, Rice G, Romero R, Saavedra JF, Illanes SE, Chaparro A. “Oral extracellular vesicles in early pregnancy can identify patients at risk of developing gestational diabetes mellitus”. PloS One (2019)

Vera N, Acuña-Gallardo S, Grünenwald F, Caceres-Verschae A, Realini O, Acuña R, Lladser A, Illanes SE, Varas-Godoy M†. “Small extracellular vesicles released from ovarian cancer stem-like cells in response to cisplatin promote the pro-tumorigenic activity of mesenchymal stem cells”. International Journal of Molecular Science (2019)

Arias M, Monteiro LJ, Acuña-Gallardo S, Varas-Godoy M, Rice GE, Monckeberg M, Díaz P, Illanes SE. “Extracellular vesicle concentration in maternal plasma as an early marker of gestational diabetes”. Rev Med Chile (2019)

Arredondo SB, Guerrero FG, Herrera-Soto A, Jensen-Flores J, Bustamante DB, Oñate-Ponce A, Henny P, Varas-Godoy M, Inestrosa NC, Varela-Nallar L. “Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by non-canonical Wnt signaling”. Stem Cells (2020)

Pérez P, Indo S, Niechi I, Huerta H, Cabello P, Aguayo F, Varas-Godoy M, Burzio VA, Tapia JC. “Endothelin-converting enzyme-1c promotes stem cell traits and aggressiveness of colorectal cancer cells”. Molecular Oncology (2020)

Lara P, Palma S, Salas-Huenuleo E, Polakovicova I, Guerrero S, Lobos-Gonzalez L, Campos A, Muñoz L, Jorquera- Cordero C, Varas-Godoy M, Cancino J, Arias E, Villegas J, Cruz LJ, Albericio F, Araya E, Corvalan AH, Quest AFG, Kogan MJ.“Gold nanoparticle based double-labelling of melanoma extracellular vesicles to determine specificity of uptake by cells and preferential accumulation in small metastatic tumors”. Journal of Nanobiotechnology (2020)

Lobos-González L, Bustos R, Campos, Silva VA, Silva V, Jeldes E, Salomon C, Varas-Godoy M, Caceres-Verschae A, Duran E, Vera T, Ezquer F, Ezquer M, Burzio VA, Villegas J. “Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells”. Scientific Reports (2020)

Olafsson EB, ten Hoeve AL, Li Wang X, Westermark L, Varas-Godoy M, Barragan A.“Convergent Met and voltage-gated Ca2+ channel signaling drives hypermigration of Toxoplasma-infected dendritic cells”. Journal of Cell Science (2020)

Monteiro L*, Varas-Godoy M*, Acuña-Gallardo S, Correa P, Passalacqua G, Monckeberg M, Rice GE, Illanes SE. “Increased circulating levels of tissue type plasminogen activator are associated with the risk of spontaneous abortion during the first semester of pregnancy”. Diagnotics (2020)

Luarte A, Henzi R, Fernández A, Gaete D, Cisternas P, Pizarro M, Luis Batiz LF, Villalobos I, Masalleras M, Vergara R, Varas-Godoy M, Abarzua-Catalan L, Herrera-Molina R, Lafourcade C, Wyneken U. “Astrocyte-derived small extracellular vesicles regulate dendritic complexity through miR-26a-5p activity”. Cells (2020)

Acuña R, Varas-Godoy M, Alfaro I, Berthoud V, Retamal M. “Connexin-46 Contained in Extracellular Vesicles Enhance Malignancy in Breast Cancer Cells”. Biomolecules (2020)

Toledo EM, Yang S, Gyllborg D, van Wijk KE, Sinha I, Varas-Godoy M, Grigsby CL, Lönnerberg P, Islam S, Steffensen KR, Linnarsson S, Arenas E. “Srebf1 Controls Midbrain Dopaminergic Neurogenesis”. Cell Reports (2020)

Pérez-Moreno P, Quezada-Meza C, Chavez-Almarza C, Niechi I, Silva-Pavez E, Trigo C, Aguayo F, Jara L, Cáceres-Verschae A, Varas-Godoy M, Diaz VM, Garcia De Herreros A, Burzio VA, Tapia JC. “Phosphorylation of endothelin-converting enzyme-1c at serines 18 and 20 by CK2 promotes aggressiveness traits in colorectal cancer cells”. Frontiers in Oncology (2020)

Alvarez-Astudillo F, Garrido D, Varas-Godoy M, Gutiérrez JL, Villanueva RA, Loyola A. “The Histone Variant H3.3 Regulates the Transcription of the Hepatitis B Virus”. Annals of Hepatology (2020)

Bhandage AK, Olivera GC, Kanatani S, Thompson E, Loré K, Varas-Godoy M, Barragan A.“A motogenic GABAergic system of mononuclear phagocytes facilitates dissemination of coccidian parasites”. eLife (2020)

Rivas S, Silva P, Reyes M, Sepúlveda H, Solano L, Acuña J, Guerrero M, Varas-Godoy M, Quest AFG, Montecino M, Torres VA. “The RabGEF ALS2 is a hypoxia inducible target associated with the acquisition of aggressive traits in tumor cells”. Scientific Reports (2020)

Caviedes A, Maturana B, Corvalán K, Engler A, Gordillo F, Varas-Godoy M, Smalla K-H, Batiz LF, Lafourcade C, Kaehne T, Wyneken U.“eNOS-dependent S-nitrosylation of the NF-κB subunit p65 has neuroprotective effects”. Cell Death & Disease (2021)

Cerda-Troncoso C, Varas-Godoy M†, Burgos PV†. “Pro-tumoral functions of autophagy receptors in the modulation of cancer progression”. Frontiers in Oncology (2021)

Carreño D, Corro N, Cerda-Infante J, Echeverría C, Asencio-Barría C, Torres-Estay V, Mayorga-Weber G, Rojas P, Véliz L, Cisternas P, Montecinos V.P, San Francisco I, Varas-Godoy M, Sotomayor P, Castro M.A, Nualart F, Inestrosa N, Godoy A .“Dietary Fructose Promote Prostate Cancer Growth”. Cancer Research (2021)

Cordero P, Guerrero A, De los Reyes M, Varas-Godoy M, Cortez J, Torres CG, Parraguez VH, Peralta OA. “Overexpression of DAZL, STRA8 and BOULE Genes and Treatment with BMP4 or Retinoic Acid Modulate the Expression of Germ Cell Genes in Bovine Fetal Mesenchymal Stem Cells”. Frontiers in Veterinary Science (2021)

Torres VI, Barrera DP, Varas-Godoy M, Arancibia D, Inestrosa NC.“Selective surface and intraluminal localization of Wnt ligands on small extracellular vesicles released by HT-22 hippocampal neurons”. Frontiers in Cell and Developmental Biology (2021)

Aguilar G, Córdova F, Koning T, Sarmiento J, Boric M, Birukov K, Cancino J, Varas-Godoy M, Soza A, Guimaraes Alves N, Mujica P, Duran W, Ehrenfeld P, Sánchez F. “TNF-α activated eNOS signaling increases leukocyte adhesion through the S-nitrosylation pathway”. AJP-Heart and Circulatory Physiology (2021)

Acuña RA*, Varas-Godoy M*, Herrera-Sepulveda D, Retamal MA. “Connexin46 expression enhances cancer stem cell and epithelial-to-mesenchymal transition characteristics of human breast cancer MCF-7 cells”. International Journal of Molecular Science (2021)

Guerra MV, Cáceres MI, Herrera-Soto A, Arredondo SB, Varas-Godoy M, Van Zundert B, Varela-Nallar L. “H3K9 methyltransferases Suv39h1 and Suv39h2 control the differentiation of neural progenitor cells in the adult hippocampus”. Frontiers in Cell and Developmental Biology (2022)

Vargas G, Cortés O, Arias-Muñoz E, Hernandez S, Cerda-Troncoso C, Hernandez L, Gonzalez A, Tatham M, Bustamante HA, Retamal C, Cancino J, Varas-Godoy M, Hay RT, Rojas-fernandez A, Cavieres V, Burgos PV. “Negative modulation of macroautophagy by stabilized HERPUD1 is counteracted by an increased ER-lysosomal network with impact in drug-induced stress cell survival”. Frontiers in Cell and Developmental Biology (2022)

Zhang S, Miyakawa A, Wickström M, Dyberg C, Louhivuori L, Varas-Godoy M, Kemppainen K, Kanatani S, Kaczynska D, Dehnisch Ellström I, Elfman L, Kronqvist P, Repo H, Mikoshiba K, Sahlgren C, Johnsen JI, Uhlén P. “GIT1 Protects Against Breast Cancer Growth Through Negative Regulation of Notch”. Nature Communication (2022)

Simon L, Sanhueza S, Gaete-Ramirez B, Varas-Godoy M†, Quest AF†. “Role of the pro-inflammatory tumor microenvironment in extracellular vesicle-mediated transfer of therapy resistance”. Frontiers in Oncology (2022)

Other publications

Original published articles:  * equal contribution, † corresponding author.

Google Scholar: https://scholar.google.es/citations?user=4cZPsgkAAAAJ&hl=en

 

Principal investigator

Manuel Varas

+56984294529

manuel.varas@uss.cl

Biography

Comparte: