José Miguel Lizcano de Vega

José Miguel  Lizcano de Vega

 

José Miguel Lizcano de Vega

Academic Staff

Phone:
+34 935 813 076

Email:
josemiguel.lizcano@uab.cat

Adress:

Department of Biochemistry and Molecular Biology
Institut de Neurociències
Faculty  of Medicine (room M2-110)
Universitat Autònoma de Barcelona (UAB)
Bellaterra Campus 08193-Cerdanyola del Vallés

Area

Thesis number in address


Jose M Lizcano received the PhD degree (Biochemistry) at the UAB. He completed his training at the Laboratory of Prof. Keith F Tipton, Trinity College Dublin, Ireland (1995-96). Then he moved to the MRC Protein Phosphorylation Unit at the University of Dundee (UK), to work as MRC Research Associate with Professors Sir Philip Cohen and Dario Alessi. There, he dissected cellular signalling pathways ruled by protein kinases that play fundamental roles in driving pathologies, such as diabetes or cancer (1998-2004). In 2004, he obtained a Ramón y Cajal Senior Researcher Tenure Track contract and he was recruited by the Institut de Neurociències, where he founded the Protein Kinase and Signal Transduction Laboratory. From 2005, he is Associate Professor at the UAB Department of Biochemistry & Molecular Biology, where he acted as Deputy Director (2008-2014).

He has published more than 65 papers in refereed journals, and his work has been cited more than 4.600 times (Scholar).

Dr. Lizcano coordinates the Signaling and New Therapeutic Targets (SINDATER) research group and leads his own laboratory:

 

 

 

Laboratory members:

Dr Pau Muñoz Guardiola

Dr Guillermo Yoldi

Nora Diéguez Martínez

Sergio Espinosa Gil

Elisabet Megías Roda

Alexandre Deber

Andrea Pasquier

Raquel Sal

 

Former members:
Dra. Tatiana Erazo      

Dra. Ana Moreno Iglesias
Dra. Margarita Espona

Dra. Arantza Rodríguez Asiaín

Dr. Gerard Ruiz Babot

 

RESEARCH INTERESTS

Lizcano’s Lab is interested in dissecting new cellular signaling pathways that control cancer cell proliferation and differentiation.  We collaborate with academics and Biopharma Companies to perform preclinical development of new anticancer drugs. Specifically, we are interested in deciphering the role of the new MAP kinase ERK5 (a MAP kinase) in cancer proliferation and survival. We are also interested in modulation of autophagy and endoplasmic reticulum (ER) stress as new strategies to tackle cancer

We use two different perspectives to approach fundamental problems:

a) Basic Research. Dissection of the mechanisms by ERK5 kinase (as well other kinases) exert a control on the proliferation and survival of tumor cells. We have contributed to propose new molecular mechanism for regulation of protein kinase Akt; discovered that tumor suppressor kinase LKB1 functions as a master kinase; or more recently, we have established a new mechanism by which ERK5 translocates to the nucleus and regulates the proliferation of tumor cells regardless of its enzymatic activity.

b) Research directed to pharmacological intervention in cancer. We are involved in potentiating translational aspects of our resources. We actively collaborate with Ability Pharmaceuticals SL in the preclinical/clinical development of the new antitumor drug ABTL0812, which it is Clinical Trial Phase II to treat cancer patients with advanced endometrial and squamous NSCLC cancers (NCT02201823). We have discovered a new cellular signaling pathway by which ABTL0812 exerts its antitumor action: by altering the sphingolipidoma of cancer cells, ABTL0812 induces a sustained activation of ER stress and UPR, as well as inhibition of the Akt/mTORC1, which ultimately results in activation of cytotoxic autophagy. Finally, we actively collaborate with other academic laboratories characterizing new ERK5 inhibitors with anticancer activity.


CURRENT WORK

1) Role of MAP kinase ERK5 in cancer cell proliferation and survival (neuroblastoma and endometrial cancer)

2) Preclinical development of new drugs for cancer therapy. Antitumoral drugs that exert their action by activating cytotoxic autophagy. New ERK5 inhibitors with anti-cancer activity.


COLLABORATORS

  • Prof. Nathanael Gray, Harvard Medical School, Boston, MA, USA
  • Prof. Dario Alessi, University of Dundee, UK
  • Prof. Ricardo Biondi, University Hospital Frankfurt, Germany
  • Dr. Elisabetta Rovida. University of Florence, Italy
  • Prof. Guillermo Velasco, Universidad Complutense Madrid
  • Prof. Antonio Zorzano. Institute for Research in Biomedicine (IRB), Barcelona
  • Dr. Miguel Segura, Vall d’Hebron Institut de Recerca (VHIR), Barcelona

 

FUNDING

 

 

  • Muñoz-Guardiola P, Casas J, Megías-Roda E, Solè S, pérez-Montoyo H, Yeste-Velasco M, Erazo T, Diéguez-Martínez N, Espinosa-Gil S, Muñoz-Pinedo C, Yoldi G, Abad JL, Segura MF, Moran T, Romero M, Bosch-Barrera, Oaknin A, Alfón J, Domènech C, Fabriàs G, Velasco G, Lizcano JM. (2020) The anti-cancer drug aBTL0812 induces ER-stress-mediated cytotoxic autophagyy increasing dihydroceramide levels in cancer cells. Autophagy. In press. doi: 0.1080/15548627.2020.1761651
  • Ferguson FM, Nabet B, Raghavan S, Liu Y, Leggett AL, Kuljanin M, Kalekar RL, Yang A, He S, Wang J, Ng RWS, Sulahian R, Li L, Poulin EJ, Huang L, Koren J, Dieguez-Martinez N, Espinosa S, Zeng Z, Corona CR, Vasta JD, Ohi R, Sim T, Kim ND, Harshbarger W, Lizcano JM, Robers MB, Muthaswamy S, Lin CY, Look AT, Haigis KM, Mancias JD, Wolpin BM, Aguirre AJ, Hahn WC, Westover KD, Gray NS. (2020) Discovery of a selective inhibitor of doublecortin like kinase 1. Nature Chemical Biology. doi:10.1038/s41589-020-0506-0
  • Erazo T, Espinosa-Gil S, Diéguez-Martínez N, Gómez N, Lizcano JM. (2020) SUMOylation Is Required for ERK5 Nuclear Translocation and ERK5-Mediated Cancer Cell Proliferation. International Journal of Molecular Sciences 21(6):2203. doi:10.3390/ijms21062203
  • Hermanova I, Zúñiga-García P, Caro-Maldonado A, Fernandez-Ruiz S, Salvador F, Martín-Martín N, Zabala-Letona A, Nuñez-Olle M, Torrano V, Camacho L, Lizcano JM, Talamillo A, Carreira S, Gurel B, Cortazar AR, Guiu M, López JI, Martinez-Romero A, Astobiza I, Valcarcel-Jimenez L, Lorente M, Arruabarrena-Aristorena A, Velasco G, Gomez-Muñoz A, Suárez-Cabrera C, Lodewijk I, Flores JM, Sutherland JD, Barrio R, de Bono JS, Paramio JM, Trka J, Graupera M, Gomis RR, Carracedo A. (2020) Genetic Manipulation of LKB1 Elicits Lethal Metastatic Prostate Cancer. Journal of Experimental Medicine 217(6):e20191787. doi:10.1084/jem.20191787
  • Coppa A, Guha S, Fourcade S, Parameswaran J, Ruiz M, Moser AB, Schlüter A, Murphy MP, Lizcano JM, Miranda-Vizuete A, Dalfó E, Pujol A. (2020) The Peroxisomal Fatty Acid Transporter ABCD1/PMP-4 Is Required in the C. Elegans Hypodermis for Axonal Maintenance: A Worm Model for Adrenoleukodystrophy. Free Radic Biol Med S0891-5849(19)32464-5. doi:10.1016/j.freeradbiomed.2020.01.177
  • López-Plana A, Fernández-Nogueira P, Muñoz-Guardiola P, Solé-Sánchez S, Megías-Roda E, Pérez-Montoyo H, Jauregui P, Yeste-Velasco M, Gómez-Ferreria M, Erazo T, Ametller E, Recalde-Percaz L, Moragas-Garcia N, Noguera-Castells A, Mancino M, Morán T, Nadal E, Alfón J, Domènech C, Gascon P, Lizcano JM, Fuster G, Bragado P. (2020) The Novel Proautophagy Anticancer Drug ABTL0812 Potentiates Chemotherapy in Adenocarcinoma and Squamous Nonsmall Cell Lung Cancer. International Journal of Cancer. doi: 10.1002/ijc.32865.
  • Felip I, Moiola CP, Megino-Luque C, Lopez-Gil C, Cabrera S, Solé-Sánchez S, Muñoz-Guardiola P, Megias-Roda E, Pérez-Montoyo H, Alfon J, Yeste-Velasco M, Santacana M, Dolcet X, Reques A, Oaknin A, Rodríguez-Freixinos V, Lizcano JM, Domènech C, Gil-Moreno A, Matias-Guiu X, Colas E, Eritja N. (2019) Therapeutic Potential of the New TRIB3-mediated Cell Autophagy Anticancer Drug ABTL0812 in Endometrial Cancer. Gynecolical Oncology 153:425-435. doi: 10.1016/j.ygyno.2019.03.002.
  • Wang J, Erazo T, Ferguson FM, Buckley DL, Gomez N, Muñoz-Guardiola P, Diéguez-Martínez N, Deng X, Hao M, Massefski W, Fedorov O, Offei-Addo NK, Park PM, Dai L, DiBona A, Becht K, Kim ND, McKeown MR, Roberts JM, Zhang J, Sim T, Alessi DR, Bradner JE, Lizcano JM, Blacklow SC, Xu X, Gray NS. (2018) Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido-benzodiazipinones as Inhibitors of Kinases and Bromodomains. ACS Chemical Biology 13:2438-2448. doi:10.1021/acschembio.7b00638.
  • Cuenda A, Lizcano JM, Lozano J. (2017) Editorial: Mitogen Activated Protein Kinases. Front Cell Dev Biol. 5:80. doi:10.3389/fcell.2017.00080.
  • Erazo T, Llorente M, Lopez A, Muñoz-Guardiola P, Fernández-Nogueira P, Bragado P,  Salazar M, Hernandez-Losa J, Bayascas JR,  Cortal M, Vidal L, Gascon P, Gomez-Ferreria M,  Alfón J,  Velasco G, Domenech C & Lizcano JM. (2016) The new antitumor drug ABTL0812 inhibits Akt/mTORC1 axis by upregulating Tribbles-3 pseudokinase. Clinical Cancer Research 22:2508-19. doi:10.1158/1078-0432.CCR-15-1808.
  • Gomez N, Erazo T, Lizcano JM.(2016) ERK5 and Cell Proliferation: Nuclear Localization Is What Matters. Front Cell Dev Biol. 4:105. doi:10.3389/fcell.2016.00105.
  • Cordón-Barris L, Pascual-Guiral S, Yang S, Giménez-Llort L, Lope-Piedrafita S, Niemeyer C, Claro E, Lizcano JM, Bayascas JR. (2016) Mutation of the 3-Phosphoinositide-Dependent Protein Kinase 1 (PDK1) Substrate-Docking Site in the Developing Brain Causes Microcephaly With Abnormal Brain Morphogenesis Independently of Akt, Leading to Impaired Cognition and Disruptive Behavior. Mol Cell Biol. 36:2967-2982. doi:10.1128/MCB.00230-16.
  • Erazo T, Moreno A, Ruiz-Babot G, Rodríguez-Asiain A, Morrice NA, Espadamala J, Bayascas JR, Gómez N, Lizcano JM. (2013) Canonical and kinase activity-independent mechanisms for extracellular signal-regulated kinase 5 (ERK5) nuclear translocation require dissociation of Hsp90 from the ERK5-Cdc37 complex. Mol Cell Biol. 33:1671-86. doi: 10.1128/MCB.01246-12
  • Elkins JM, Wang J, Deng X, Pattison MJ, Arthur JS, Erazo T, Gomez N, Lizcano JM, Gray NS, Knapp S. (2013) X-ray crystal structure of ERK5 (MAPK7) in complex with a specific inhibitor. J Med Chem. 56: 4413-21. doi:10.1021/jm4000837
  • Rodríguez-Asiain A, Ruiz-Babot G, Romero W, Cubí R, Erazo T, Biondi RM, Bayascas JR, Aguilera J, Gómez N, Gil C, Claro E, Lizcano JM. (2011) Brain specific kinase-1 BRSK1/SAD-B associates with lipid rafts: modulation of kinase activity by lipid environment. Biochim Biophys Acta. 1811:1124-35. doi:10.1016/j.bbalip.2011.10.004
  • Paoletti, P; Vila, I; Rifé, M; Lizcano, JM; Alberch, J; Ginés, S (2009) Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease neurodegeneration: the role of p25/cyclin-dependent kinase 5. Journal of Neuroscience 28: 10090-101.doi:10.1523/JNEUROSCI.3237-08.2008
  • Lizcano JM, Goransson O, Toth R, Deak M, Morrice N, Boudeau J,  Hawley SA, Udd L, Makela T, Hardie DG, Alessi DR (2004) LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO Journal. 23: 833-843.
  • Biondi RM, Komander D, Thomas CC, Lizcano JM, Deak M, Alessi DR, van Aalten DM. (2002) High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site. EMBO Journal, 21: 4219-28.                                                                              
  • Lizcano JM, Alessi DR. (2002) The insulin signaling pathway. Current Biology, 12: R236-8.  

See all Jose M Lizcano publications at PubMed.

 

 

 

Institut de Neurociències
Tel: 93 581 3861 / Fax: +34 93 581 3327

Facultat de Medicina. Edifici M-1
Avinguda de Can Domènech - Campus de la UAB · 08193
Bellaterra (Cerdanyola del Vallès) · Barcelona