Prostate cancer Lab
|
Current Lab Members
Alvaro Aytes- Group Leader Katia Ruggero - Postoc Sonia Farran Matas - MSc student / PhD candidate Xiang chen - Lab technician Adrián Martínez Tebar - PhD student To learn more about who we are and what we do, please visit us at http://www.alvaroayteslab.eu/ |
|
Dr. Aytes´s laboratory aims at uncovering new mechanisms driving cancer progression and metastasis and to elucidate how these mechanisms contribute to the emergence of therapeutic resistance. The lab´s main focus is on prostate cancer utilizing genetically-engineered mice (GEM) to model relevant molecular alterations, thereby recapitulating the progression pathway observed in human prostate cancer. In addition, our lab utilizes gene regulatory network-based approaches to conduct cross-species studies to identify actionable targets that can be validated in preclinical models.
|
Prostate cancer is the most commonly diagnosed malignancy among men and the second leading cause of cancer-related mortality in developed countries. While a majority of patients face very favorable outcomes and are unlikely to succumb from the disease, a subset will progress to more aggressive forms that are highly metastatic and lethal. In these cases, treatment options are initially effective but therapeutic resistance eventually occurs leading to an associated mortality.
|
|
|
|
The research in our lab focuses on understanding how the landscape of genetic and epigentic alterations shape dinamic changes in gene repulatory programs that ultimately result in the selection or emergence of therapeutic resistance to standard of care treatments, mainly androgen deprivation and androgen receptor targeting approaches. The specific research lines in the lab cover different aspects:
|
2015
Mitrofanova A*, Aytes A*, Zou M, Shen MM, Abate-Shen C, Califano A. Predicting Drug Response in Human Prostate Cancer from Preclinical Analysis of In Vivo Mouse Models. Cell Rep. 2015 Sep 29;12(12):2060-71
Goodwin JF, Kothari V, Drake JM, Zhao S, Dylgjeri E, Dean JL, Schiewer MJ, McNair C, Jones JK, Aytes A, Magee MS, Snook AE, Zhu Z, Den RB, Birbe RC, Gomella LG, Graham NA, Vashisht AA, Wohlschlegel JA, Graeber TG, Karnes RJ, Takhar M, Davicioni E, Tomlins SA, Abate-Shen C, Sharifi N, Witte ON, Feng FY, Knudsen KE. DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis. Cancer Cell. 2015 Jul 13;28(1):97-113.
2014
Aytes, A., Mitrofanova, A, Lefebvre, C, Alvarez, MJ, Castillo-Martin, M., Zheng, T., Eastham, JA, Gopalan, A., Pienta, K.J., Shen, M.M., Califano, A., & Abate-Shen, C. (2014) Cross-species analysis of genome-wide regulatory networks identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy. Cancer Cell 25(5); 638-651
Highlights in: Lokody, I. (2014), Nature Reviews Cancer, 7, 450
2013
Aytes, A., Mitrofanova, A., Kinkade, C.W., Lefebvre, C., Lei, M., Phelan, V., Lekaye, H.C., Koutcher, J.A., Cardiff, R.D., Califano, A., Shen, M.M., & Abate-Shen, C. (2013) ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer. Proc Natl Acad Sci U S A 110(37):E3506-3515.
Highlights in: Baker, S.J. and Reddy, E.P. (2013), Proc. of the Nat. Acad. of Sciences USA, 37, 14819
Grabowska, M.M. et al., (2014), Cancer and Metastasis Reviews, 33, 377
Irshad, S., Bansal, M., Castillo-Martin, M., Zheng, T., Aytes, A., Wenske, S., Le Magnen, C., Guarnieri, P., Sumazin, P., Benson, M.C., Shen, M.M., Califano, A., & Abate-Shen, C. (2013) A molecular signature predictive of indolent prostate cancer. Science Translational Medicine 5(202):202ra122.
2012
Wang, J., Kobayashi, T., Floc'h, N., Kinkade, C.W., Aytes, A., Dankort, D., Lefebvre, C., Mitrofanova, A., Cardiff, R.D., McMahon, M., Califano, A., Shen, M.M., & Abate-Shen, C. (2012) B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer. Cancer Res 72(18):4765-4776.
Floc'h, N., Kinkade, C.W., Kobayashi, T., Aytes, A., Lefebvre, C., Mitrofanova, A., Cardiff, R.D., Califano, A., Shen, M.M., & Abate-Shen, C. (2012) Dual targeting of the Akt/mTOR signaling pathway inhibits castration-resistant prostate cancer in a genetically engineered mouse model. Cancer Res 72(17):4483-4493.
Aytes, A., Mollevi, D.G., Martinez-Iniesta, M., Nadal, M., Vidal, A., Morales, A., Salazar, R., Capella, G., & Villanueva, A. (2012) Stromal interaction molecule 2 (STIM2) is frequently overexpressed in colorectal tumors and confers a tumor cell growth suppressor phenotype. Molecular carcinogenesis 51(9):746-753.
2011
Melo, S., Villanueva, A., Moutinho, C., Davalos, V., Spizzo, R., Ivan, C., Rossi, S., Setien, F., Casanovas, O., Simo-Riudalbas, L., Carmona, J., Carrere, J., Vidal, A., Aytes, A., Puertas, S., Ropero, S., Kalluri, R., Croce, C.M., Calin, G.A., & Esteller, M. (2011) Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing. Proc Natl Acad Sci U S A 108(11):4394-4399.
Maxwell, C.A., Benitez, J., Gomez-Baldo, L., Osorio, A., Bonifaci, N., Fernandez-Ramires, R., Costes, S.V., Guino, E., Chen, H., Evans, G.J., Mohan, P., Catala, I., Petit, A., Aguilar, H., Villanueva, A., Aytes, A., et al. (2011) Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer. PLoS Biol 9(11):e1001199.
2009.
Mollevi, D.G., Aytes, A., Berdiel, M., Padulles, L., Martinez-Iniesta, M., Sanjuan, X., Salazar, R., & Villanueva, A. (2009) PRL-3 overexpression in epithelial cells is induced by surrounding stromal fibroblasts. Molecular Cancer 8:46.
2008.
Mollevi, D.G., Aytes, A., Padulles, L., Martinez-Iniesta, M., Baixeras, N., Salazar, R., Ramos, E., Figueras, J., Capella, G., & Villanueva, A. (2008) PRL-3 is essentially overexpressed in primary colorectal tumours and associates with tumour aggressiveness. British journal of cancer 99(10):1718-1725.
2007
Fernandez-Majada, V., Aguilera, C., Villanueva, A., Vilardell, F., Robert-Moreno, A., Aytes, A., Real, F.X., Capella, G., Mayo, M.W., Espinosa, L., & Bigas, A. (2007) Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer. Proc Natl Acad Sci U S A 104(1):276-281.
Mitrofanova A*, Aytes A*, Zou M, Shen MM, Abate-Shen C, Califano A. Predicting Drug Response in Human Prostate Cancer from Preclinical Analysis of In Vivo Mouse Models. Cell Rep. 2015 Sep 29;12(12):2060-71
Goodwin JF, Kothari V, Drake JM, Zhao S, Dylgjeri E, Dean JL, Schiewer MJ, McNair C, Jones JK, Aytes A, Magee MS, Snook AE, Zhu Z, Den RB, Birbe RC, Gomella LG, Graham NA, Vashisht AA, Wohlschlegel JA, Graeber TG, Karnes RJ, Takhar M, Davicioni E, Tomlins SA, Abate-Shen C, Sharifi N, Witte ON, Feng FY, Knudsen KE. DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis. Cancer Cell. 2015 Jul 13;28(1):97-113.
2014
Aytes, A., Mitrofanova, A, Lefebvre, C, Alvarez, MJ, Castillo-Martin, M., Zheng, T., Eastham, JA, Gopalan, A., Pienta, K.J., Shen, M.M., Califano, A., & Abate-Shen, C. (2014) Cross-species analysis of genome-wide regulatory networks identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy. Cancer Cell 25(5); 638-651
Highlights in: Lokody, I. (2014), Nature Reviews Cancer, 7, 450
2013
Aytes, A., Mitrofanova, A., Kinkade, C.W., Lefebvre, C., Lei, M., Phelan, V., Lekaye, H.C., Koutcher, J.A., Cardiff, R.D., Califano, A., Shen, M.M., & Abate-Shen, C. (2013) ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer. Proc Natl Acad Sci U S A 110(37):E3506-3515.
Highlights in: Baker, S.J. and Reddy, E.P. (2013), Proc. of the Nat. Acad. of Sciences USA, 37, 14819
Grabowska, M.M. et al., (2014), Cancer and Metastasis Reviews, 33, 377
Irshad, S., Bansal, M., Castillo-Martin, M., Zheng, T., Aytes, A., Wenske, S., Le Magnen, C., Guarnieri, P., Sumazin, P., Benson, M.C., Shen, M.M., Califano, A., & Abate-Shen, C. (2013) A molecular signature predictive of indolent prostate cancer. Science Translational Medicine 5(202):202ra122.
2012
Wang, J., Kobayashi, T., Floc'h, N., Kinkade, C.W., Aytes, A., Dankort, D., Lefebvre, C., Mitrofanova, A., Cardiff, R.D., McMahon, M., Califano, A., Shen, M.M., & Abate-Shen, C. (2012) B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer. Cancer Res 72(18):4765-4776.
Floc'h, N., Kinkade, C.W., Kobayashi, T., Aytes, A., Lefebvre, C., Mitrofanova, A., Cardiff, R.D., Califano, A., Shen, M.M., & Abate-Shen, C. (2012) Dual targeting of the Akt/mTOR signaling pathway inhibits castration-resistant prostate cancer in a genetically engineered mouse model. Cancer Res 72(17):4483-4493.
Aytes, A., Mollevi, D.G., Martinez-Iniesta, M., Nadal, M., Vidal, A., Morales, A., Salazar, R., Capella, G., & Villanueva, A. (2012) Stromal interaction molecule 2 (STIM2) is frequently overexpressed in colorectal tumors and confers a tumor cell growth suppressor phenotype. Molecular carcinogenesis 51(9):746-753.
2011
Melo, S., Villanueva, A., Moutinho, C., Davalos, V., Spizzo, R., Ivan, C., Rossi, S., Setien, F., Casanovas, O., Simo-Riudalbas, L., Carmona, J., Carrere, J., Vidal, A., Aytes, A., Puertas, S., Ropero, S., Kalluri, R., Croce, C.M., Calin, G.A., & Esteller, M. (2011) Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing. Proc Natl Acad Sci U S A 108(11):4394-4399.
Maxwell, C.A., Benitez, J., Gomez-Baldo, L., Osorio, A., Bonifaci, N., Fernandez-Ramires, R., Costes, S.V., Guino, E., Chen, H., Evans, G.J., Mohan, P., Catala, I., Petit, A., Aguilar, H., Villanueva, A., Aytes, A., et al. (2011) Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer. PLoS Biol 9(11):e1001199.
2009.
Mollevi, D.G., Aytes, A., Berdiel, M., Padulles, L., Martinez-Iniesta, M., Sanjuan, X., Salazar, R., & Villanueva, A. (2009) PRL-3 overexpression in epithelial cells is induced by surrounding stromal fibroblasts. Molecular Cancer 8:46.
2008.
Mollevi, D.G., Aytes, A., Padulles, L., Martinez-Iniesta, M., Baixeras, N., Salazar, R., Ramos, E., Figueras, J., Capella, G., & Villanueva, A. (2008) PRL-3 is essentially overexpressed in primary colorectal tumours and associates with tumour aggressiveness. British journal of cancer 99(10):1718-1725.
2007
Fernandez-Majada, V., Aguilera, C., Villanueva, A., Vilardell, F., Robert-Moreno, A., Aytes, A., Real, F.X., Capella, G., Mayo, M.W., Espinosa, L., & Bigas, A. (2007) Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer. Proc Natl Acad Sci U S A 104(1):276-281.
Title: Mecanismos epigenéticos de resistencia a la castración en cancer de próstata: oportunidades terapéuticas en combinación con antagonistas del receptor de andrógenos.
Funding Agency: Instituto de Salud Carlos III.
Principal Investigator: Alvaro Aytes Meneses.
Period: 01/01/2017- 31/12/2019.
Funding: 110.715 €. Coordinator.
Title: Screening signature of endometrial and ovarian cancers: options for early detection (screenwide).
Funding Agency: Instituto de Salud Carlos III.
Principal Investigator: Silvia SanJose.. Alvaro Aytes as Co-investigator
Period: 01/01/2017- 31/12/2019.
Funding: 559.025,5 €. (114.000 €. for Aytes Lab)
Title: Identification of molecular drivers of metastatic prostate cancer: the role of FOXM1 and CENPF in the deregulation of the epigenetic control of gene expression (CP15/00090)
Funding Agency: Instituto de Salud Carlos III.
Principal Investigator: Alvaro Aytes
Period: 29/01/2016-28/01/2019
Funding: 121.500 €.
Title: Investigating causal mechanisms and novel therapeutic targets in CRPC after AR blockade failure
Funding Agency: European Association of Urology Research Foundation (EAU-RF)
Principal Investigator: Alvaro Aytes
Period: 01/01/2016- 31/12/2018
Funding: 240.000 €
Title: A systems approach to identify molecular drivers and new therapeutic targets in metastatic prostate cancer
Funding Agency: MINECO Programa Retos
Principal Investigator: Alvaro Aytes
Period: 01/09/2015-31/08/2018
Funding: 170.000 € Declined for incompatibility with Miguel Servet grant
Title: Mecanismos epigenéticos de resistencia a la castración en cancer de próstata: oportunidades terapéuticas en combinación con antagonistas del receptor de andrógenos.
Funding Agency: Fundación BBVA
Principal Investigator: Alvaro Aytes
Period: 01/10/2016-31/03/2018
Funding: 40.000 €
Funding Agency: Instituto de Salud Carlos III.
Principal Investigator: Alvaro Aytes Meneses.
Period: 01/01/2017- 31/12/2019.
Funding: 110.715 €. Coordinator.
Title: Screening signature of endometrial and ovarian cancers: options for early detection (screenwide).
Funding Agency: Instituto de Salud Carlos III.
Principal Investigator: Silvia SanJose.. Alvaro Aytes as Co-investigator
Period: 01/01/2017- 31/12/2019.
Funding: 559.025,5 €. (114.000 €. for Aytes Lab)
Title: Identification of molecular drivers of metastatic prostate cancer: the role of FOXM1 and CENPF in the deregulation of the epigenetic control of gene expression (CP15/00090)
Funding Agency: Instituto de Salud Carlos III.
Principal Investigator: Alvaro Aytes
Period: 29/01/2016-28/01/2019
Funding: 121.500 €.
Title: Investigating causal mechanisms and novel therapeutic targets in CRPC after AR blockade failure
Funding Agency: European Association of Urology Research Foundation (EAU-RF)
Principal Investigator: Alvaro Aytes
Period: 01/01/2016- 31/12/2018
Funding: 240.000 €
Title: A systems approach to identify molecular drivers and new therapeutic targets in metastatic prostate cancer
Funding Agency: MINECO Programa Retos
Principal Investigator: Alvaro Aytes
Period: 01/09/2015-31/08/2018
Funding: 170.000 € Declined for incompatibility with Miguel Servet grant
Title: Mecanismos epigenéticos de resistencia a la castración en cancer de próstata: oportunidades terapéuticas en combinación con antagonistas del receptor de andrógenos.
Funding Agency: Fundación BBVA
Principal Investigator: Alvaro Aytes
Period: 01/10/2016-31/03/2018
Funding: 40.000 €
|
We are recruiting!
- Highly motivated postdocs with a track record of early achievements (publications, fellowships,...) in cancer related research. Interested candidates should send their CV and three reference letters to Alvaro Aytes. Computational and bioinformatics backgrounds are specially encouraged to apply. - Positions are opened to talented and pasioned graduated students who want to embark in a PhD program in cancer biology. Please contact Alvaro Aytes for further details |
