Mecanismos moleculares asociados a reprogramación metabólica en células de cáncer en respuesta a diferentes tipos de estrés.
Posibles implicancias terapéuticas en la inhibición de la función de componentes asociados a la regulación del metabolismo de las células de cáncer.

ANID CHILE-FONDECYT 1201215 2020-2024
Mechanisms of regulation of cancer cell metabolism counteracting oxidative stress
Investigador principal.

CONYCIT CHILE-FONDECYT 1191172 2019-2023
Unraveling the role and mechanism of sall2 transcription factor in colorectal cancer.
Co-investigador.

CONICYT CHILE-FONDECYT 1160731 2016-2020
Molecular mechanisms of cancer cell resistance to metabolic stress: the role of Nuak1 signaling. Investigador principal.

CONICYT CHILE-FONDECYT 1151031 2015-2019
Regulation and function of the Sall2 transcription factor during cellular stress.
Co-investigador.

Universidad de Concepción/ Proyecto VRID-Enlace. 214.037.018-1.0 2014-2016
Caracterización molecular y funcional de una variante nuclear de catepsina L en células de cáncer de colon. Co-investigador.

FIC Bío-Bío CHILE 30116843-0 2012-2016
Transferencia Bioterio al Servicio de Empresas y Laboratorios.
Co-investigador.

CONICYT CHILE-FONDECYT 1120923 2012-2016
Interrupted rheb-to-ampk feedback signaling with cytoplasmic p27 retention: mechanisms and biological consequences. Investigador principal.

Universidad de Concepción/ Proyecto VRID-Enlace 212.037.017-1.0. 2012-2013
Integrating signaling pathways, transcriptional regulation and cell behavior in the study of mechanisms of carcinogen. Co-investigador.

Universidad de Concepción/ DIUC 210.037.011-1.0 2011-2012
Regulation of the cell-cycle inhibitor p27Kip1 by aberrant Rheb GTPase.
Investigador principal.

UCSF Academic Senate Individual Investigator Grant USA 2007-2008
Alterations of TSC2/Rheb signaling in colorectal cancer.
Investigador principal

DOD/ Congressionally Directed Medical Research Program USA TS043006 2005-2008
Functional Relevance of the Ras-related GTPase Rheb in Tuberous Sclerosis.
Investigador principal.

National Centers of Excellence in Women’s Health USA 2001-2002
Role of Rap and Estrogen in Lymphangioleiomyomatosis. Investigador principal.

Publicaciones (# indica corresponding author)
Pinto C, Medinas DB, Fuentes-Villalobos F, Maripillán J, Castro AF, Martínez AD, Osses N, Hetz C, Henríquez JP#. β-catenin aggregation in models of ALS motor neurons: GSK3β inhibition effect and neuronal differentiation. Neurobiol Dis. 2019 Jun 7;130:104497.

Palma M, Riffo EN, Suganuma T, Washburn MP, Workman JL, Pincheira R, Castro AF#. Identification of a nuclear localization signal and importin beta members mediating NUAK1 nuclear import inhibited by oxidative stress. J Cell Biochem. 2019 Sep;120(9):16088-16107.

Fuentes-Villalobos F, Farkas C, Riquelme-Barrios S, Armijo ME, Soto-Rifo R, Pincheira R, Castro AF#. DISC1 promotes translation maintenance during sodium arsenite-induced oxidative stress. Biochim Biophys Acta Gene Regul Mech. 2019 Jun;1862(6):657-669.

Farkas C, Fuentes-Villalobos F, Rebolledo-Jaramillo B, Benavides F, Castro AF, Pincheira R#. Streamlined computational pipeline for genetic background characterization of genetically engineered mice based on next generation sequencing data. BMC Genomics. 2019 Feb 12;20(1):131.

Silva-Pavez E, Villar P, Trigo C, Caamaño E, Niechi I, Pérez P, Muñoz JP, Aguayo F, Burzio VA, Varas-Godoy M, Castro AF, Colombo MI, Tapia JC#. CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells. Cell Death Dis. 2019 Jan 25;10(2):73.

Hepp MI, Escobar D, Farkas C, Hermosilla VE, Álvarez C, Amigo R, Gutiérrez JL, Castro AF, Pincheira R#. A Trichostatin A (TSA)/Sp1-mediated mechanism for the regulation of SALL2 tumor suppressor in Jurkat T cells. Biochim Biophys Acta Gene Regul Mech. 2018 May 18. pii: S1874-9399(18)30028-2.

Hermosilla V, Salgado G, Riffo E, Escobar D, Hepp MI, Farkas C, Galindo M, Morín V, García-Robles MA, Castro AF, Pincheira R#. SALL2 represses cyclins D1 and E1 expression and restrains G1/S cell cycle transition and cancer-related phenotypes. Mol Oncol. 2018 Jun;12(7):1026-1046.

Hermosilla V, Hepp M, Escobar D, Farkas C, Riffo E, Castro AF, Pincheira R#. Developmental Sall2 transcription factor: a new player in cancer. Carcinogenesis 2017 Jul 1;38(7):680-690.

Campos T, Ziehe J, Fuentes-Villalobos F, Riquelme O, Peña D, Troncoso R, Lavandero S, Morin V, Pincheira R, Castro AF#. Rapamycin requires AMPK activity and p27 expression for promoting autophagy-dependent Tsc2-null cell survival. Biochim Biophys Acta. 2016 Jun;1863(6 Pt A):1200-7.

Armijo ME*, Campos T*, Fuentes-Villalobos F, Palma ME, Pincheira R, Castro AF#. Rheb signaling and tumorigenesis: mTORC1 and new horizons. International Journal of Cancer 2016 Apr 15;138(8):1815-23. *co-first authors

Campos T, Ziehe J, Palma M, Escobar D, Tapia JC, Pincheira R, Castro AF#. Rheb promotes cancer cell survival through p27Kip1-dependent activation of autophagy. Mol Carcinog. 2016 Feb;55(2):220-9

Escobar D, Hepp M, Farkas C, Campos T, Sodir N, Morales M, Alvarez C, Swigart L, Evan G, Gutierrez J, Nishinakamura R, Castro AF, Pincheira R#. Sall2 is required for pro-apoptotic Noxa expression and genotoxic stress-induced apoptosis by Doxorubicin. Cell Death & Disease 2015 Jul 16;6:e1816.

Farkas C, Martins CP, Escobar D, Hepp MI, Castro AF, Evan G, Gutiérrez JL, Warren R, Donner DB, Pincheira R#. (2013) Wild type p53 transcriptionally represses the SALL2 transcription factor under genotoxic stress. PLoS One. 2013 Sep 6;8(9):e73817.

Castro AF#, Campos T, Babcock JT, Armijo ME, Martínez-Conde A, Pincheira R, Quilliam LA. (2012) M-Ras induces Ral and JNK activation to regulate MEK/ERK-independent gene expression in MCF-7 breast cancer cells. J Cell Biochem. 113(4):1253-64.

Lacher M, Pincheira R and Castro AF#. (2011) Consequences of interrupted Rheb-to-AMPK feedback signalling in tuberous sclerosis complex and cancer. Small GTPases. 2(4):211-216.

Lacher M, Pincheira R, Zhu Z, Camoretti-Mercado M, Matli M, Warren RS, and Castro AF#. (2010) Rheb activates AMPK and reduces p27Kip1 levels in Tsc2-null cells via mTORC1-independent mechanisms: implications for cell proliferation and tumorigenesis. Oncogene 29(50):6543-56.

Pincheira R, Castro AF, Ozes ON, Idumalla PS, Donner D#. (2008) TNFR1 complexes and uses Jak2 and c-Src to selectively engage signaling pathways that regulate transcription factor activity. J. Immunol.;181(2):1288-98.

Li Y, Asuri S, Rebhun JF, Castro AF, Paranavitana NC, Quilliam LA#. (2006) The RAP1 guanine nucleotide exchange factor Epac2 couples cyclic AMP and Ras signals at the plasma membrane. J Biol Chem; 281(5):2506-14.

Castro AF, Rebhun JF, Quilliam LA# (2005) Measuring Ras-family GTP levels in vivo-running hot and cold. Methods. 37: 190-6.
Felekkis KN, Narsimhan RP, Near R, Castro AF, Zheng Y, Quilliam LA, Lerner A#. (2005) AND-34 activates phosphatidylinositol 3-kinase and induces anti-estrogen resistance in a SH2 and GDP exchange factor-like domain-dependent manner. Mol Cancer Res;3(1):32-41.

Castro AF#, Rebhun JF, Clark GJ, Quilliam LA. (2003) Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner. J Biol Chem, Accelerated publication;278(35):32493-6. #corresponding author

Wilkes DM, Wang C, Aristimuño PC, Castro AF, Altenberg GA#. (2002) Nucleotide triphosphatase activity of the N-terminal nucleotide-binding domains of the multidrug resistance proteins P-glycoprotein and MRP1. Biochem Biophys Res Commun; 296(2):388-94.

Quilliam LA#, Rebhun JF, and Castro AF. (2002) A growing family of guanine nucleotide exchange factors is responsible for activation of Ras family GTPases. Prog Nucleic Acid Res Mol Biol: Academic Press, 71: 391-444.

Quilliam LA#, Rebhun JF, Zong H, and Castro AF (2001). Analyses of M-Ras/R-Ras3 Signaling and Biology. Methods Enzymol : Academic Press, 333: 187-202.

Rebhun JF, Castro AF*, Quilliam LA. Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. J Biol Chem, Nov/10/2000;275(45):34901-8. *co-first author

Castro AF, Horton JK, Vanoye CG, Altenberg GA#. Mechanism of inhibition of P-glycoprotein-mediated drug transport by protein kinase C blockers. Biochem Pharmacol, Dec/1/1999;58(11):1723-33.

Quilliam LA#, Castro AF, Rogers-Graham KS, Martin CB, Der CJ, Bi C. (1999) M-Ras/R-Ras3, a transforming ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6. J Biol Chem; 274(34):23850-7.

Wang C, Castro AF, Wilkes DM, Altenberg GA#. (1999) Expression and purification of the first nucleotide-binding domain and linker region of human multidrug resistance gene product: comparison of fusions to glutathione S-transferase, thioredoxin and maltose-binding protein. Biochem J; 338 ( Pt 1):77-81.

Vanoye CG, Castro AF, Pourcher T, Reuss L, Altenberg GA#. (1999) Phosphorylation of P-glycoprotein by PKA and PKC modulates swelling-activated Cl- currents. Am J Physiol-CELL PH; 276(2 Pt 1):C370-8.

Castro AF#, Amorena C, Müller A, Ottaviano G, Tellez-Iñon MT, Taquini AC. (1998) Extracellular ATP and bradykinin increase cGMP in vascular endothelial cells via activation of PKC. Am J Physiol-CELL PH, 275(1 Pt 1):C113-9. #corresponding author

Horton JK, Thimmaiah KN, Altenberg GA, Castro AF, Germain GS, Gowda GK, Houghton PJ#. (1997) Characterization of a novel bisacridone and comparison with PSC 833 as a potent and poorly reversible modulator of P-glycoprotein. Mol Pharmacol, 52(6):948-57.

Vanoye CG, Castro AF, Altenberg GA, and Reuss L#.(1997) Regulation of swelling-activated Cl- channels by P-glycoprotein (Pgp).(abstract) FASEB J. (11): A304.

Amorena C#, Castro AF. (1997) Control of proximal tubule acidification by the endothelium of the peritubular capillaries. Am J Physio-REG l, 272(2 Pt 2):R691-4.

Castro AF, Altenberg GA#. (1997) Inhibition of drug transport by genistein in multidrug-resistant cells expressing P-glycoprotein. Biochem Pharmacol, 53(1):89-93.

Castro AF, and Altenberg GA#. (1996) Drug binding by an N-terminal fragment of human P-glycoprotein (Pgp) distal to transmembrane segment(TM)4. (abstract) Proc. Am. Assoc. Cancer Res. (37): 327.

Amorena CE, Castro AF, Muller A, Villamil MF#. (1990) Direct vascular effects in the rat of the vehicles used for the intravenous and oral administration of cyclosporin A. Clinical Science ;(79):149-154.

Transducción de Señales y Cáncer.

2019-presente Director Programa Doctorado en Ciencias Biológicas, área Biología Celular y Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción.

2017-2019 Miembro Titular Comité Evaluación Académica, Facultad de Ciencias Ambientales, Universidad de Concepción

2018 Director Grupo de Estudio Biología 3 del programa FONDECYT/CONICYT

2016-2017 Miembro titular del Grupo de Estudio Biología 3 del programa FONDECYT/CONICYT

2014 Miembro Jurado Medalla Dr. Herman Niemeyer/Sociedad de Bioquímica y Biología Molecular de Chile

2013-2014 Director Regional Sociedad de Bioquímica y Biología Molecular de Chile

2013-2014 Miembro Titular Comité Evaluación Académica, Facultad de Ciencias Biológicas, Universidad de Concepción

2012-presente Miembro Comité Biología Celular y Molecular. Programa Formación de Capital Humano Avanzado (PFCHA)/CONICYT.

2012-2019 Miembro Comité Doctorado en Ciencias Biológicas, área Biología Celular y Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción.

2009 Miembro Grupo de Estudio DOD/ Congressionally Directed Medical Research Program USA.