Researh & development

Translational Research


How do our cells sense and respond to internal and external signals? They use very sophisticated networks of molecules known as intracellular signaling pathways. These pathways are not only important for normal cells but also for cells that are at the center of disease conditions. Therefore, the pharmacological modulation of these networks could be a way to develop novel therapies to treat critically ill patients with diseases for which there are limited treatment options. Our lab, which is composed of a unique group of cell biologists, biochemists, pharmacologists and chemists, focuses on the validation and modification of known signaling pathways that can be involved in diseases. Our goal is to bring projects from the bench to the clinic and minimize the time to do so.


Bernales S, Papa FR, Walter P.Intracellular signaling by the unfolded protein response. Annu Rev Cell Dev Biol. 2006;22:487-508. Review. PubMed PMID:16822172 | PDF | Abstract

Walther TC, Brickner JH, Aguilar PS, Bernales S, Pantoja C, Walter P. Eisosomes mark static sites of endocytosis. Nature. 2006 Feb 23;439(7079):998-1003. PubMed PMID: 16496001 | PDF | Abstract

Bernales S, McDonald KL, Walter P. Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS Biol. 2006 Nov;4(12):e423. PubMed PMID: 17132049; PubMed Central PMCID: PMC1661684 | PDF | Abstract

Bernales S, Schuck S, Walter P. ER-phagy: selective autophagy of the endoplasmic reticulum. Autophagy. 2007 May-Jun;3(3):285-7. Epub 2007 May 1. PubMed PMID: 17351330 | PDF | Abstract

Steele JW, Ju S, Lachenmayer ML, Liken J, Stock A, Kim SH, Delgado LM, Alfaro IE, Bernales S, Verdile G, Bharadwaj P, Gupta V, Barr R, Friss A, Dolios G, Wang R, Ringe D, Protter AA, Martins RN, Ehrlich ME, Yue Z, Petsko GA, Gandy S. Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain. Mol Psychiatry. 2013 Aug;18(8):882-8. doi:10.1038/mp.2012.115. Epub 2012 Aug 7. PubMed PMID: 22869031; PubMed Central PMCID: PMC3523214 | PDF | Abstract

Guerrero J, Alfaro IE, Gómez F, Protter AA, Bernales S. Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer. Prostate. 2013 Sep;73(12):1291-305. doi:10.1002/pros.22674. Epub 2013 Jun 13. PubMed PMID: 23765603 | PDF | Abstract

Cochrane DR, Bernales S, Jacobsen BM, Cittelly DM, Howe EN, D'Amato NC, Spoelstra NS, Edgerton SM, Jean A, Guerrero J, Gómez F, Medicherla S, Alfaro IE, McCullagh E, Jedlicka P, Torkko KC, Thor AD, Elias AD, Protter AA, Richer JK. Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Res. 2014 Jan 22;16(1):R7. doi: 10.1186/bcr3599. PubMed PMID: 24451109; PubMed Central PMCID: PMC3978822 | PDF | Abstract

Mendez AS, Alfaro J, Morales-Soto MA, Dar AC, McCullagh E, Gotthardt K, Li H, Acosta-Alvear D, Sidrauski C, Korennykh AV, Bernales S, Shokat KM, Walter P.Endoplasmic reticulum stress-independent activation of unfolded protein response kinases by a small molecule ATP-mimic. Elife. 2015 May 19;4. doi:10.7554/eLife.05434. PubMed PMID: 25986605; PubMed Central PMCID: PMC4436593

Jadhavar PS, Ramachandran SA, Riquelme E, Gupta A, Quinn KP, Shivakumar D, Ray S, Zende D, Nayak AK, Miglani SK, Sathe BD, Raja M, Farias O, Alfaro I, Belmar S, Guerrero J, Bernales S, Chakravarty S, Hung DT, Lindquist JN, Rai R. Targeting prostate cancer with compounds possessing dual activity as androgen receptor antagonists and HDAC6 inhibitors. Bioorg Med Chem Lett. 2016 Nov 1;26(21):5222-5228. doi: 10.1016/j.bmcl.2016.09.058. Epub 2016 Oct 4. PubMed PMID: 27717544

Krukowski K., Nolan A., Frias ES., Grue K., Becker M., Ureta G., Delgado L., Bernales S., Sohal VS., Walter P. (2020) Integrated stress response inhibitor reverses sex-dependent behavioral and cell-specific deficits after mild repetitive head trauma. Journal of Neurotrauma.37(1). DOI: 10.1089/neu.2019.6827

Krukowski K., Nolan A., Frias ES., Boone M., Ureta G., Grue K., Paladini MS., Elizarras E., Delgado L., Bernales S., Walter P, Rosi S. (2020) Small molecule cognitive enhancer reverses age-related memory decline in mice. Elife 2020;9:e62048. DOI: 10.7554/eLife.62048

Principal investigator

Sebastián Bernales

+56 2 2367 2086