Jose M Lizcano

Jose M Lizcano
Autonomous University of Barcelona | UAB · Vall Hebron Research Institute (VHIR) Institute of Neuroscience (INc) and Departament de Bioquimica UAB

B.Sc, PhD

About

129
Publications
33,083
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Introduction
I am interested 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 in cancer proliferation and survival. We are also interested in modulation of autophagy and endoplasmic reticulum (ER) stress as new strategies to tackle cancer
Additional affiliations
February 2005 - May 2022
Autonomous University of Barcelona
Position
  • Professor (Associate)
September 2004 - February 2005
Autonomous University of Barcelona
Position
  • Ramon y Cajal Tenuree-Track
November 2000 - September 2004
University of Dundee
Position
  • Research Associate

Publications

Publications (129)
Preprint
Full-text available
Endometrial cancer (EC) is the most common type of gynaecologic cancer in women of developed countries. Despite surgery combined with chemo-/radiotherapy regimens, overall survival of patients with high-risk EC tumors is poor, indicating a need for novel molecular therapies. The MEK5-ERK5 pathway is activated in response to growth factors and to d...
Article
Full-text available
The ERK5 MAP kinase signalling pathway drives transcription of naïve pluripotency genes in mouse Embryonic Stem Cells (mESCs). However, how ERK5 impacts on other aspects of mESC biology has not been investigated. Here, we employ quantitative proteomic profiling to identify proteins whose expression is regulated by the ERK5 pathway in mESCs. This re...
Article
Full-text available
Autophagy is a highly conserved intracellular process that preserves cellular homeostasis by mediating the lysosomal degradation of virtually any component of the cytoplasm. Autophagy is a key instrument of cellular response to several stresses, including endoplasmic reticulum (ER) stress. Cancer cells have developed high dependency on autophagy to...
Article
Full-text available
An experimental model of spinal root avulsion (RA) is useful to study causal molecular programs that drive retrograde neurodegeneration after neuron-target disconnection. This neurodegenerative process shares common characteristics with neuronal disease-related processes such as the presence of endoplasmic reticulum (ER) stress and autophagy flux b...
Conference Paper
ABTL0812 induces cytotoxic autophagy in cancer cells through the combination of ER stress induction and Akt/mTOR blockade. ABTL0812 induces ER stress mediated activation of JNK-Jun pathway and inhibition of the STAT3-IL10 axis in cancer and immune cells in vitro and induces ER stress markers TRIB3 and CHOP in white blood cells of patients with no t...
Preprint
Full-text available
The ERK5 MAP kinase signalling pathway drives transcription of naive pluripotency genes in mouse Embryonic Stem Cells (mESCs). However, how ERK5 impacts on other aspects of mESC biology has not been investigated. Here, we employ quantitative proteomic profiling to identify proteins whose expression is regulated by the ERK5 pathway in mESCs. This re...
Article
Background ABTL0812 is an autophagy inducer that promotes cancer cell death by activation of cytotoxic autophagy selectively in tumour cells. ABTL0812 induces endoplasmic reticulum stress and blocks the Akt-mTOR axis; both actions converge to activate a robust and sustained autophagy leading to cancer cell death. Preclinical data supported the init...
Cover Page
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
Neuroblastoma is the leading cause of cancer death in children aged 1 to 4 years. Particularly, five-year overall survival for high-risk neuroblastoma is below 50% with no curative options when refractory or relapsed. Most of current therapies target cell division and proliferation, thereby inducing DNA damage and programmed cell death. However, ag...
Article
Full-text available
Elucidating the contribution of somatic mutations to cancer is essential for personalized medicine. STK11 (LKB1) appears to be inactivated in human cancer. However, somatic mis-sense mutations also occur, and the role/s of these alterations to this disease remain unknown. Here, we investigated the contribution of four missense LKB1 somatic mutation...
Article
Full-text available
Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of...
Article
ABTL0812 is a first-in-class small molecule with anti-cancer activity, which is currently in clinical evaluation in a phase 2 trial in patients with advanced endometrial and squamous non-small cell lung carcinoma (NCT03366480). Previously, we showed that ABTL0812 induces TRIB3 pseudokinase expression, resulting in the inhibition of the AKT-MTORC1 a...
Article
Full-text available
Gene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkb1 alone...
Article
Full-text available
The MAP kinase ERK5 contains an N-terminal kinase domain and a unique C-terminal tail including a nuclear localization signal and a transcriptional activation domain. ERK5 is activated in response to growth factors and stresses and regulates transcription at the nucleus by either phosphorylation or interaction with transcription factors. MEK5-ERK5...
Article
Adrenoleukodystrophy is a neurometabolic disorder caused by a defective peroxisomal ABCD1 transporter of very long-chain fatty acids (VLCFAs). Its pathogenesis is incompletely understood. Here we characterize a nematode model of X-ALD with loss of the pmp-4 gene, the worm orthologue of ABCD1. These mutants recapitulate the hallmarks of X-ALD: i) VL...
Preprint
Full-text available
The MAP kinase ERK5 contains an N-terminal kinase domain and a unique C-terminal tail including a nuclear localization signal and a transcriptional activation domain. ERK5 is activated in response to growth factors and stresses, and regulates transcription at the nucleus by either phosphorylation or interaction with transcription factors. MEK5-ERK5...
Article
Around 40% of newly diagnosed lung cancer patients are stage IV, where the improvement of survival and reduction of disease‐related adverse events is the main goal for oncologists. In this scenario, we present pre‐clinical evidences supporting the use of ABTL0812 in combination with chemotherapy for treating advanced and metastatic Non‐Small‐Cell L...
Conference Paper
Introduction/Background Endometrial cancer (EC) is the most frequent of the infiltrating tumors of female genital tract. Surgical and adjuvant treatments are the cornerstone treatment for EC patients, however, the response rate to standard therapy is very limited, highlighting the need for novel and efficient treatments. ABTL0812, a small first-in-...
Article
Background: ABTL0812 is a novel anti-cancer agent that induces a strong autophagy-mediated cell death by a dual mechanism. It inhibits the Akt/mTOR axis by upregulating TRIB3, an endogenous Akt inhibitor, and induces reticular (ER)-stress. Preclinical data in squamous non-small cell lung carcinoma (Sq-NSCLC) and endometrial cancer (EC) has indicate...
Article
Objectives: The PI3K/AKT/mTOR pathway is frequently overactivated in endometrial cancer (EC). We assessed the efficacy of ABTL0812, a novel first-in-class molecule presenting a unique mechanism of action inhibiting this pathway. Methods: We investigated the effects of ABTL0812 on proliferation, cell death and modulation of intracellular signalin...
Article
Full-text available
Abstract The Tribbles (TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic t...
Data
Phylogenetic analysis of B. floridae, B. belcheri and B. lanceolatum TLRs. The phylogenetic tree was constructed by maximum-likelihood method (IQ-TREE) using TIR domain sequences of B. floridae, B. belcheri, B. lanceolatum, S. kowalevskii and representative vertebrate TLRs. D. melanogaster Toll sequence was used as an outgroup to root the tree. Seq...
Data
Phylogenetic analysis of BlTLR. The phylogenetic tree was constructed by maximum-likelihood method (IQ-TREE) using full-length protein sequences. BlTLR, BbtTLR1 and representative vertebrate TLR sequences were used in the analysis. D. melanogaster Toll was used as an outgroup to root the tree. Sequences were aligned with MAFFT choosing L-INS-i meth...
Data
TLR sequences of L. variegatus and S. kowalevskii used in the phylogenetic analysis. The TIR domain of each TLR is highlighted in yellow.
Data
Complete phylogenetic analysis of B. lanceolatum TLRs. The phylogenetic tree was constructed by IQ-TREE using full-length protein sequences. This tree is a more detailed version of the tree shown in Figure 1. All the values of SH-aLRT support and ultrafast bootstrap support are shown at the tree nodes. Outgroup, mccTLRs and 6 vertebrate TLR familie...
Data
Protein sequence identity of BlTLR and fish TLR22.
Data
Ectodomain architecture of vertebrate TLRs and BlTLR.
Data
Nucleotide and deduced amino acid sequences of BlTLR. Predicted transcription start site (TSS) is marked with a curved arrow. TATA box is boxed with a rectangle. The putative STAT5 and APIB transcription factor binding sites have a thick underline. The start codon (ATG), the stop codon (TAA) and the polyadenylation signal sequence (AATAAA) are in b...
Data
Predicted domain architecture of BlTLR protein. The domain structure was predicted using the SMART program. Signal peptide (SP), leucine-rich repeat N-terminal domain (LRRNT), leucine-rich repeat (LRR), leucine rich repeat C-terminal domain (LRRCT), Transmembrane domain (TM) and Toll/interleukin-1 receptor (TIR) domain are indicated in figure. Figu...
Data
Vertebrate and invertebrate protein sequences used in the phylogenetic analysis.
Data
Identified DNA and putative protein sequences of TLRs in B. lanceolatum. The TIR domain of each TLR is highlighted in yellow.
Article
Full-text available
Parkinson’s disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to the organization of the actin and microtubule cytoskeletons, has been suggested to participate to Parkinson’s disease pa...
Article
Full-text available
With the author(s)' decision to opt for Open Choice the copyright of the article changed on March 2018 to
Article
Brain specific kinases (BRSKs) are serine/threonine kinases, preferentially expressed in the brain after Embryonic Day 12. Although BRSKs are crucial neuronal development factors and regulation of their enzymatic activity has been widely explored, little is known of their transcriptional regulation. In this work, we show that Neuronal Growth Factor...
Article
Bromodomains have been pursued intensively over the past several years as emerging targets for the devel-opment of anti-cancer and anti-inflammatory agents. It has recently been shown that some kinase inhibitors are able to potently inhibit the bromodomains of BRD4. The clinical activities of PLK inhibitor BI-2536 and JAK2-FLT3 inhibitor TG101348 h...
Article
Background: ABTL0812 is a new chemical entity, currently in Phase I/II clinical trial for Non-Small-Cell Lung Carcinoma (NSCLC) and endometrial cancer in combination with paclitaxel and carboplatin (P/C). It has shown an excellent safety profile and signs of efficacy, as indicated by several long disease stabilizations, in a Phase I clinical trial....
Article
Background: ABTL0812 is a first-in-class anti-cancer agent with a unique mechanism of action currently in Phase Ib/IIa clinical development for endometrial cancer and squamous NSCLC. ABTL0812 successfully culminated a Phase I clinical trial showing a high safety profile and long disease stabilizations, including 14-months stabilization in a patient...
Article
Full-text available
ERK5, the last MAP kinase family member discovered, is activated by the upstream kinase MEK5 in response to growth factors and stress stimulation. MEK5-ERK5 pathway has been associated to different cellular processes, playing a crucial role in cell proliferation in normal and cancer cells by mechanisms that are both dependent and independent of its...
Article
Full-text available
The phosphoinositide 3-kinase (PI 3-kinase)/Akt signaling pathway plays essential roles during neuronal development. The 3-phosphoinositide-dependent protein kinase 1 (PDK1) coordinates the PI 3-kinase signals by activating twenty three kinases of the AGC family including Akt. Phosphorylation of a conserved docking site in the substrate is a requis...
Article
Full-text available
Purpose: ABTL0812 is a novel first-in-class, small molecule which showed anti-proliferative effect on tumor cells on phenotypic assays. Here we describe the mechanism of action this antitumor drug, which is currently in clinical development. Experimental design: We investigated the effect of ABTL0812 on cancer cell death, proliferation and modul...
Article
Full-text available
The Klotho protein is a β-glucuronidase, and its overexpression is associated with life extension. Its mechanism of action is not fully understood, although it has been recently reported that αKlotho improves synaptic and cognitive functions, and it may also influence a variety of structures and functions during CNS maturation and aging. The αKloth...
Article
Tribbles pseudokinase 3 (TRIB3) belongs to the tribbles family of pseudokinases. In this article, we summarize several observation obtained by our laboratories supporting that TRIB3 plays a crucial role in the anti-cancer activity of cannabinoids (a novel family of potential anti-cancer agents derived from marijuana) and that TRIB3 genetic inactiva...
Article
Full-text available
Background: ABTL0812 is a first-in-class orally administered compound currently in Phase I/Ib First in Human Clinical Trial in patients with advanced solid tumors (NCT02201823). ABTL0812 has cytotoxic effect on a wide range of human tumor cell lines, including those which have become resistant to standard therapy. We hereby dissect the anti-tumor a...
Article
Full-text available
Apoptotic cell death is an integral part of cell turnover in many tissues, and proper corpse clearance is vital to maintaining tissue homeostasis in all multicellular organisms. Even in tissues with high cellular turnover, apoptotic cells are rarely seen because of efficient clearance mechanisms in healthy individuals. In Caenorhabditis elegans, tw...
Article
Full-text available
The benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-one core was discovered as a novel ERK5 (also known as MAPK7 and BMK1) inhibitor scaffold, previously. Further structure-activity relationship studies of this scaffold led to the discovery of ERK5-IN-1 (26) as the most selective and potent ERK5 inhibitor reported to date. 26 potently inhibits ERK5 bioche...